A study to assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)

Study identifier:KU36-92

ClinicalTrials.gov identifier:NCT00516373

EudraCT identifier:2005-001435-29

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, Pharmacokinetic and Biological Evaluation of a Small Molecule Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP-1), KU-0059436, in Patients with Advanced Tumours.

Medical condition

ovarian neoplasms

Phase

Phase 1

Healthy volunteers

Study drug

KU-0059436 (AZD2281)(PARP inhibitor)

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 11 Jul 2005

Primary Completion Date: 17 Dec 2008

Study Completion Date: 26 Apr 2023

Study design

Allocation: Non-randomized
Endpoint Classification: Safety
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2025 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Edinburgh, United Kingdom, EH4 2XR

Location

Research Site

Szczecin, Poland, 70-115

Location

Research Site

London, United Kingdom, SM2 5NG

Location

Research Site

Brussels, Belgium, 1090

Location

Research Site

Amsterdam, Netherlands, 1066 CX

Arms	Assigned Interventions
Experimental: KU-0059436 KU-0059436 administered orally twice daily	Drug: KU-0059436 (AZD2281)(PARP inhibitor) oral Other Name: Olaparib

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First participant first visit: 11 July 2005 Last participant last protocol specified visit: 17 December 2008 This study was a multi-centre study that involved five participating sites in the United Kingdom (two study centres), the Netherlands (one study centre), Belgium (one study centre) and Poland (one study centre).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening Details: Male or female aged ≥18 years, with malignant advanced solid tumor refractory to standard therapy or no suitable effective standard therapy existed. Evaluable or measurable disease per RECIST. Adequate bone marrow, hepatic, and renal function. ECOG performance status of 0-2 at entry. Expansion phase: ovarian/breast/prostate cancer with BRCA1 or 2 mutation.

Reporting Groups

	Description
<100 mg bd	Pooled dose level of olaparib administered for 14 days, with 21 day cycles, at: - 10 mg once daily (od) - 20 mg od - 40 mg od - 80 mg od - 60 mg twice daily (bd) OR - 100 bd.
100 mg bd	Olaparib 100 mg bd for 28 days with 28 day cycles.
200 mg bd	Olaparib 200 mg bd for 28 days with 28 day cycles.
400 mg bd	Olaparib 400 mg bd for 28 days with 28 day cycles.
600 mg bd	Olaparib 600 mg bd for 28 days with 28 day cycles.

Participant Flow: Overall Study

	<100 mg bd	100 mg bd	200 mg bd	400 mg bd	600 mg bd
STARTED	22	5	58	8	5
COMPLETED	0	0	0	0	0
NOT COMPLETED	22	5	58	8	5
Progressive disease	17	5	41	6	2
Refused further treatment	1	0	2	0	2
Unacceptable toxicity	0	0	2	1	1
Intercurrent illness	1	0	1	1	0
Investigator decision	2	0	1	0	0
Death	1	0	0	0	0
Ongoing participants at time of data cut-off (17DEC08)	0	0	11	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
<100 mg bd	Pooled dose level of olaparib administered for 14 days, with 21 day cycles, at: - 10 mg once daily (od) - 20 mg od - 40 mg od - 80 mg od - 60 mg twice daily (bd) OR - 100 bd.
100 mg bd	Olaparib 100 mg bd for 28 days with 28 day cycles.
200 mg bd	Olaparib 200 mg bd for 28 days with 28 day cycles.
400 mg bd	Olaparib 400 mg bd for 28 days with 28 day cycles.
600 mg bd	Olaparib 600 mg bd for 28 days with 28 day cycles.

Baseline Measures

	<100 mg bd	100 mg bd	200 mg bd	400 mg bd	600 mg bd	Total
Number of Participants [units: Participants]	22	5	58	8	5	98
Age Categorical [units: Participants]
<=18 years	0	0	0	0	0	0
Between 18 and 65 years	15	2	48	7	5	77
>=65 years	7	3	10	1	0	21
Age Continuous [units: Years] Mean ± Standard Deviation	55.5 ± 14.55	59.6 ± 13.05	54.6 ± 9.37	56.4 ± 7.29	45.2 ± 9.50	54.7 ± 10.88
Sex: Female, Male [units: Participants]
Female	12	3	53	7	2	77
Male	10	2	5	1	3	21
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	0	1	1	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	2	0	3	0	0	5
White	20	5	52	6	5	88
More than one race	0	0	0	0	0	0
Unknown or Not Reported	0	0	2	1	0	3
ECOG Performance Status ^[1] [units: Participants]
PS = 0	7	1	16	2	1	27
PS = 1	12	3	41	5	4	65
PS = 2	3	1	1	1	0	6
BRCA status [units: Participants]
BRCA 1/2 Mutated	2	1	50	6	1	60
BRCA 1/2 Normal	1	1	2	0	0	4
Unknown	19	3	6	2	4	34
Cancer Primary Site [units: Participants]
Ovary	6	1	40	5	1	53
Breast	2	0	9	1	1	13
Prostate	1	1	2	0	0	4
Other	13	3	7	2	3	28

Outcome Measures

1. Primary Outcome Measure: Safety Endpoint - Summary of Adverse Events [ Time Frame: Safety data was collected from the time informed consent was given, throughout the treatment period and up to and including the 30 day follow-up period. ]

Measure Type	Primary
Measure Name	Safety Endpoint - Summary of Adverse Events
Measure Description	The safety and tolerability profile of olaparib was assessed by adverse events (AEs), laboratory tests, physical examination and vital signs. The maximum tolerated dose (MTD) was defined as 400 mg bd and the 200 mg bd dose of olaparib was chosen for further assessment of the tolerability and efficacy of olaparib. AEs are further described in the "Adverse Events" section.
Time Frame	Safety data was collected from the time informed consent was given, throughout the treatment period and up to and including the 30 day follow-up period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
<100 mg bd	Pooled dose level of olaparib administered for 14 days, with 21 day cycles, at: - 10 mg once daily (od) - 20 mg od - 40 mg od - 80 mg od - 60 mg twice daily (bd) OR - 100 bd.
100 mg bd	Olaparib 100 mg bd for 28 days with 28 day cycles.
200 mg bd	Olaparib 200 mg bd for 28 days with 28 day cycles.
400 mg bd	Olaparib 400 mg bd for 28 days with 28 day cycles.
600 mg bd	Olaparib 600 mg bd for 28 days with 28 day cycles.
Safety Evaluable Population	All participants who received any study medication (all dose levels)
Safety evaluable ovarian cancer BRCA 1/2 mutated participants	Sub-set of safety evaluable ovarian BRCA 1/2 mutated participants (all dose levels)

Measured Values

	<100 mg bd	100 mg bd	200 mg bd	400 mg bd	600 mg bd	Safety Evaluable Population	Safety evaluable ovarian cancer BRCA 1/2 mutated participants
Number of Participants Analyzed [units:participants]	22	5	58	8	5	98	49
Safety Endpoint - Summary of Adverse Events [units: Number of participants with events]
Any Treatment-emergent adverse events (TEAEs)	22	5	58	8	5	98	49
Drug-Related TEAEs	15	3	53	7	5	83	43
TEAEs of CTCAE Grade 3 or 4	11	4	31	7	5	58	28
Drug-Related TEAEs CTCAE Grade 3 or 4	0	0	17	3	3	23	14
TEAEs of CTCAE Grade 3, 4 or 5	11	4	31	7	5	58	28
Drug-Related TEAEs CTCAE Grade 3, 4 or 5	0	0	17	3	3	23	14
TEAEs with Outcome=Death	2	0	6	1	1	10	5
SAEs (including events with outcome=death)	5	3	24	7	3	42	21
SAEs with Outcome Other than Death	4	3	24	7	3	41	21
TEAE Leading to Discontinuation (of Treatment)	4	1	11	4	1	21	10
Drug-Related TEAEs Leading to Discontinuation	0	0	3	1	1	5	1
Drug-Related TEAEs with Outcome=Death	0	0	0	0	0	0	0
Drug-Related SAEs	0	0	9	2	3	14	6
Drug-Related SAEs Leading to Discontinuation	0	0	2	1	1	4	1
Dose-limiting toxicities	0	0	0	1	2	3	1

No statistical analysis provided for Safety Endpoint - Summary of Adverse Events

2. Secondary Outcome Measure: Efficacy Endpoint - Overall Best Response [ Time Frame: Tumor evaluation was performed at baseline, at the end of Cycle 2, every two cycles thereafter for individuals who were receiving benefit from the study drug, and at the end of study (30 days post last dose). ]

Measure Type	Secondary
Measure Name	Efficacy Endpoint - Overall Best Response
Measure Description	Evaluation of tumour response was a secondary study objective. The primary measure of tumour response was the Overall Best Response reported after every two cycles of study drug until week 24 then every 12 weeks until confirmed progressive disease. Responses were confirmed at least four weeks (28 days) later for those participants with an initial positive response. Participants with measurable disease were assessed by the international criteria proposed by the Response Evaluation Criteria in Solid Tumours (RECIST) Committee
Time Frame	Tumor evaluation was performed at baseline, at the end of Cycle 2, every two cycles thereafter for individuals who were receiving benefit from the study drug, and at the end of study (30 days post last dose).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
<100 mg bd	Pooled dose level of olaparib administered for 14 days, with 21 day cycles, at: - 10 mg once daily (od) - 20 mg od - 40 mg od - 80 mg od - 60 mg twice daily (bd) OR - 100 bd.
100 mg bd	Olaparib 100 mg bd for 28 days with 28 day cycles.
200 mg bd	Olaparib 200 mg bd for 28 days with 28 day cycles.
400 mg bd	Olaparib 400 mg bd for 28 days with 28 day cycles.
600 mg bd	Olaparib 600 mg bd for 28 days with 28 day cycles.
Intent-to-treat (ITT) population	All participants who received study treatment, whether or not they fulfilled the eligibility criteria
ITT ovarian cancer BRCA 1/2 mutated participants	Sub-set of ITT ovarian BRCA 1/2 mutated participants (all dose levels)
ITT prostate BRCA 1/2 mutated participants	Sub-set of ITT prostate cancer BRCA 1/2 mutated participants (all dose levels)
ITT breast BRCA 1/2 mutated participants	Sub-set of ITT breast cancer BRCA 1/2 mutated participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Refractory participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Refractory participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Resistant participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Resistant participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants (all dose levels)

Measured Values

	<100 mg bd	100 mg bd	200 mg bd	400 mg bd	600 mg bd	Intent-to-treat (ITT) population	ITT ovarian cancer BRCA 1/2 mutated participants	ITT prostate BRCA 1/2 mutated participants	ITT breast BRCA 1/2 mutated participants	ITT ovarian BRCA 1/2 mutated Platinum Refractory participants	ITT ovarian BRCA 1/2 mutated Platinum Resistant participants	ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants
Number of Participants Analyzed [units:participants]	22	5	58	8	5	98	49	2	7	13	23	13
Efficacy Endpoint - Overall Best Response [units: Percentage of participants with response] Number (95% Confidence Interval)
Overall Response (CR + PR)	4.5 (0.8 to 21.8)	0.0 (0.0 to 43.4)	17.2 (9.6 to 28.9)	37.5 (13.7 to 69.4)	0.0 (0.0 to 43.4)	14.3 (8.7 to 22.6)	24.5 (14.6 to 38.1)	0.0 (0.0 to 65.8)	14.3 (2.6 to 51.3)	0.0 (0.0 to 22.8)	30.4 (15.6 to 50.9)	38.5 (17.7 to 64.5)
Complete Response (CR)	0.0 (0.0 to 14.9)	0.0 (0.0 to 43.4)	3.4 (1.0 to 11.7)	0.0 (0.0 to 32.4)	0.0 (0.0 to 43.4)	2.0 (0.6 to 7.1)	2.0 (0.4 to 10.7)	0.0 (0.0 to 65.8)	14.3 (2.6 to 51.3)	0.0 (0.0 to 22.8)	0.0 (0.0 to 14.3)	7.7 (1.4 to 33.3)
Partial Response (PR)	4.5 (0.8 to 21.8)	0.0 (0.0 to 43.4)	13.8 (7.2 to 24.9)	37.5 (13.7 to 69.4)	0.0 (0.0 to 43.4)	12.2 (7.1 to 20.2)	22.4 (13.0 to 35.9)	0.0 (0.0 to 65.8)	0.0 (0.0 to 35.4)	0.0 (0.0 to 22.8)	30.4 (15.6 to 50.9)	30.8 (12.7 to 57.6)
Stable Disease (SD)	9.1 (2.5 to 27.8)	0.0 (0.0 to 43.4)	27.6 (17.8 to 40.2)	0.0 (0.0 to 32.4)	20.0 (3.6 to 62.4)	19.4 (12.8 to 28.3)	18.4 (10.0 to 31.4)	100.0 (34.2 to 100.0)	42.9 (15.8 to 75.0)	23.1 (8.2 to 50.3)	13.0 (4.5 to 32.1)	23.1 (8.2 to 50.3)
Progressive Disease (PD)	72.7 (51.8 to 86.8)	100.0 (56.6 to 100.0)	55.2 (42.5 to 67.3)	37.5 (13.7 to 69.4)	40.0 (11.8 to 76.9)	59.2 (49.3 to 68.4)	53.1 (39.4 to 66.3)	0.0 (0.0 to 65.8)	42.9 (15.8 to 75.0)	69.2 (42.4 to 87.3)	52.2 (33.0 to 70.8)	38.5 (17.7 to 64.5)

No statistical analysis provided for Efficacy Endpoint - Overall Best Response

3. Secondary Outcome Measure: Efficacy Endpoint - Duration of Response [ Time Frame: Tumour evaluation was performed at baseline, at the end of Cycle 2, every two cycles thereafter for individuals who were receiving benefit from the study drug, and at the end of study (30 days post last dose). ]

Measure Type	Secondary
Measure Name	Efficacy Endpoint - Duration of Response
Measure Description	The duration of response was derived for participants with measurable disease at baseline and a confirmed on-study response of Complete Response (RECIST - CR) or Partial Response (RECIST - PR). Duration of Response was calculated from the first day a confirmed PR or CR was observed until recurrence or PD was objectively documented (including symptomatic progression), or death due to disease progression (only including deaths during the on-study period).
Time Frame	Tumour evaluation was performed at baseline, at the end of Cycle 2, every two cycles thereafter for individuals who were receiving benefit from the study drug, and at the end of study (30 days post last dose).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Intent-to-treat (ITT) population	All participants who received study treatment, whether or not they fulfilled the eligibility criteria
ITT ovarian cancer BRCA 1/2 mutated participants	Sub-set of ITT ovarian BRCA 1/2 mutated participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Resistant participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Resistant participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants (all dose levels)

Measured Values

	Intent-to-treat (ITT) population	ITT ovarian cancer BRCA 1/2 mutated participants	ITT ovarian BRCA 1/2 mutated Platinum Resistant participants	ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants
Number of Participants Analyzed [units:participants]	14	12	7	5
Efficacy Endpoint - Duration of Response [units: Days] Median (95% Confidence Interval)	252 (170 to 601)	252 (170 to 601)	252 (113 to 253)	601 (112 to 601)

No statistical analysis provided for Efficacy Endpoint - Duration of Response

4. Secondary Outcome Measure: Efficacy Endpoint - Duration of Stable Disease [ Time Frame: Tumour evaluation was performed at baseline, at the end of Cycle 2, every two cycles thereafter for individuals who were receiving benefit from the study drug, and at the end of study (30 days post last dose). ]

Measure Type	Secondary
Measure Name	Efficacy Endpoint - Duration of Stable Disease
Measure Description	The duration of SD was derived for participants with measurable disease at baseline and an on-study response of SD per RECIST. Duration of SD was calculated from the date of first study drug administration until PD was objectively documented (including symptomatic progression), or death due to disease progression (only including deaths during the on-study period).
Time Frame	Tumour evaluation was performed at baseline, at the end of Cycle 2, every two cycles thereafter for individuals who were receiving benefit from the study drug, and at the end of study (30 days post last dose).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Intent-to-treat (ITT) population	All participants who received study treatment, whether or not they fulfilled the eligibility criteria
ITT ovarian cancer BRCA 1/2 mutated participants	Sub-set of ITT ovarian BRCA 1/2 mutated participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Resistant participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Resistant participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants (all dose levels)
ITT breast BRCA 1/2 mutated participants	Sub-set of ITT breast cancer BRCA 1/2 mutated participants (all dose levels)

Measured Values

	Intent-to-treat (ITT) population	ITT ovarian cancer BRCA 1/2 mutated participants	ITT ovarian BRCA 1/2 mutated Platinum Resistant participants	ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants	ITT breast BRCA 1/2 mutated participants
Number of Participants Analyzed [units:participants]	19	9	3	3	3
Efficacy Endpoint - Duration of Stable Disease [units: Days] Median (95% Confidence Interval)	196 (177 to 312)	218 (177 to 220)	219 (177 to 220)	161 (161 to 218)	196 (163 to 196)

No statistical analysis provided for Efficacy Endpoint - Duration of Stable Disease

5. Secondary Outcome Measure: Efficacy Endpoint - Time to Disease Progression [ Time Frame: Tumour evaluation was performed at baseline, at the end of Cycle 2, every two cycles thereafter for individuals who were receiving benefit from the study drug, and at the end of study (30 days post last dose). ]

Measure Type	Secondary
Measure Name	Efficacy Endpoint - Time to Disease Progression
Measure Description	Time to Disease Progression was calculated from the date of first study drug administration until objective progressive disease (RECIST - PD)/symptomatic deterioration or death due to progression (only including deaths during the on-study period) was observed. Participants who did not have progression during the study were censored at the last tumour assessment date or date of death from other causes. If two or more consecutive scheduled assessments had no data (incomplete assessment, not assessed, or missing), the Time to PD was calculated at the time of the last prior assessment with valid data. If a single assessment had no data, this assessment was ignored and any prior and subsequent assessments could be used to determine the Time to PD. Participants with measurable disease were assessed by the international criteria proposed by the RECIST Committee.
Time Frame	Tumour evaluation was performed at baseline, at the end of Cycle 2, every two cycles thereafter for individuals who were receiving benefit from the study drug, and at the end of study (30 days post last dose).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Intent-to-treat (ITT) population	All participants who received study treatment, whether or not they fulfilled the eligibility criteria
ITT ovarian cancer BRCA 1/2 mutated participants	Sub-set of ITT ovarian BRCA 1/2 mutated participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Refractory participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Refractory participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Resistant participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Resistant participants (all dose levels)
ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants	Sub-set of ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants (all dose levels)

Measured Values

	Intent-to-treat (ITT) population	ITT ovarian cancer BRCA 1/2 mutated participants	ITT ovarian BRCA 1/2 mutated Platinum Refractory participants	ITT ovarian BRCA 1/2 mutated Platinum Resistant participants	ITT ovarian BRCA 1/2 mutated Platinum Sensitive participants
Number of Participants Analyzed [units:participants]	98	49	13	23	13
Efficacy Endpoint - Time to Disease Progression [units: Days] Median (95% Confidence Interval)	84 (54 to 115)	115 (94 to 161)	54 (35 to 107)	121 (91 to 219)	161 (109 to 336)

No statistical analysis provided for Efficacy Endpoint - Time to Disease Progression

6. Secondary Outcome Measure: PK Endpoint - Cmax at Cycle 1 Day 1 (C1D1) [ Time Frame: PK samples were collected at C1D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration. ]

Measure Type	Secondary
Measure Name	PK Endpoint - Cmax at Cycle 1 Day 1 (C1D1)
Measure Description	Dose normalised maximum plasma concentration (Cmax) following administration of a single dose of olaparib (C1D1).
Time Frame	PK samples were collected at C1D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
PK 10 mg	Sub-set of PK population with dose level = 10 mg (PK population includes all participants who provided PK samples)
PK 20 mg	Sub-set of PK population with dose level = 20 mg
PK 40 mg	Sub-set of PK population with dose level = 40 mg
PK 60 mg	Sub-set of PK population with dose level = 60 mg
PK 80 mg	Sub-set of PK population with dose level = 80 mg
PK 100 mg	Sub-set of PK population with dose level = 100 mg (regardless of cycle length)
PK 200 mg	Sub-set of PK population with dose level = 200 mg
PK 400 mg	Sub-set of PK population with dose level = 400 mg
PK 600 mg	Sub-set of PK population with dose level = 600 mg

Measured Values

	PK 10 mg	PK 20 mg	PK 40 mg	PK 60 mg	PK 80 mg	PK 100 mg	PK 200 mg	PK 400 mg	PK 600 mg
Number of Participants Analyzed [units:participants]	3	3	5	4	3	9	33	8	5
PK Endpoint - Cmax at Cycle 1 Day 1 (C1D1) [units: ug/mL] Mean (Standard Deviation)	0.03930 (0.01214)	0.05983 (0.03225)	0.04945 (0.01126)	0.04425 (0.01443)	0.04417 (0.008938)	0.03623 (0.01623)	0.02665 (0.01436)	0.01548 (0.003013)	0.01836 (0.005868)

No statistical analysis provided for PK Endpoint - Cmax at Cycle 1 Day 1 (C1D1)

7. Secondary Outcome Measure: PK Endpoint - AUC(0-10h) at C1D1 [ Time Frame: PK samples were collected at C1D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration. ]

Measure Type	Secondary
Measure Name	PK Endpoint - AUC(0-10h) at C1D1
Measure Description	Dose normalised area under the plasma concentration-time curve (AUC) to 10 hours post-dose.
Time Frame	PK samples were collected at C1D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
PK 10 mg	Sub-set of PK population with dose level = 10 mg (PK population includes all participants who provided PK samples)
PK 20 mg	Sub-set of PK population with dose level = 20 mg
PK 40 mg	Sub-set of PK population with dose level = 40 mg
PK 60 mg	Sub-set of PK population with dose level = 60 mg
PK 80 mg	Sub-set of PK population with dose level = 80 mg
PK 100 mg	Sub-set of PK population with dose level = 100 mg (regardless of cycle length)
PK 200 mg	Sub-set of PK population with dose level = 200 mg
PK 400 mg	Sub-set of PK population with dose level = 400 mg
PK 600 mg	Sub-set of PK population with dose level = 600 mg

Measured Values

	PK 10 mg	PK 20 mg	PK 40 mg	PK 60 mg	PK 80 mg	PK 100 mg	PK 200 mg	PK 400 mg	PK 600 mg
Number of Participants Analyzed [units:participants]	3	3	5	4	3	9	33	8	5
PK Endpoint - AUC(0-10h) at C1D1 [units: ug/mL] Mean (Standard Deviation)	0.1313 (0.04917)	0.2023 (0.09507)	0.2500 (0.05535)	0.1582 (0.03465)	0.1745 (0.07583)	0.1931 (0.1275)	0.1302 (0.08316)	0.08121 (0.02839)	0.1111 (0.04341)

No statistical analysis provided for PK Endpoint - AUC(0-10h) at C1D1

8. Secondary Outcome Measure: PK Endpoint - Cmax at C1D14 [ Time Frame: PK samples were collected at C1D14 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration. ]

Measure Type	Secondary
Measure Name	PK Endpoint - Cmax at C1D14
Measure Description	Dose normalised Cmax at steady state (Cmax ss) following administration of multiple doses of olaparib (C1D14).
Time Frame	PK samples were collected at C1D14 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
PK 10 mg	Sub-set of PK population with dose level = 10 mg (PK population includes all participants who provided PK samples)
PK 40 mg	Sub-set of PK population with dose level = 40 mg
PK 60 mg	Sub-set of PK population with dose level = 60 mg
PK 80 mg	Sub-set of PK population with dose level = 80 mg
PK 100 mg	Sub-set of PK population with dose level = 100 mg (regardless of cycle length)
PK 200 mg	Sub-set of PK population with dose level = 200 mg
PK 400 mg	Sub-set of PK population with dose level = 400 mg
PK 600 mg	Sub-set of PK population with dose level = 600 mg

Measured Values

	PK 10 mg	PK 40 mg	PK 60 mg	PK 80 mg	PK 100 mg	PK 200 mg	PK 400 mg	PK 600 mg
Number of Participants Analyzed [units:participants]	3	4	3	3	7	28	6	3
PK Endpoint - Cmax at C1D14 [units: ug/mL] Mean (Standard Deviation)	0.05233 (0.02348)	0.04456 (0.002961)	0.03478 (0.004158)	0.06067 (0.008408)	0.03829 (0.01241)	0.03358 (0.01882)	0.01969 (0.005099)	0.02046 (0.007511)

No statistical analysis provided for PK Endpoint - Cmax at C1D14

9. Secondary Outcome Measure: PK Endpoint - AUC(0-10h) at C1D14 [ Time Frame: PK samples were collected at C1D14 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration. ]

Measure Type	Secondary
Measure Name	PK Endpoint - AUC(0-10h) at C1D14
Measure Description	Dose normalised AUC(0-10h) at C1D14
Time Frame	PK samples were collected at C1D14 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
PK 10 mg	Sub-set of PK population with dose level = 10 mg (PK population includes all participants who provided PK samples)
PK 40 mg	Sub-set of PK population with dose level = 40 mg
PK 60 mg	Sub-set of PK population with dose level = 60 mg
PK 80 mg	Sub-set of PK population with dose level = 80 mg
PK 100 mg	Sub-set of PK population with dose level = 100 mg (regardless of cycle length)
PK 200 mg	Sub-set of PK population with dose level = 200 mg
PK 400 mg	Sub-set of PK population with dose level = 400 mg
PK 600 mg	Sub-set of PK population with dose level = 600 mg

Measured Values

	PK 10 mg	PK 40 mg	PK 60 mg	PK 80 mg	PK 100 mg	PK 200 mg	PK 400 mg	PK 600 mg
Number of Participants Analyzed [units:participants]	3	4	3	3	7	28	6	3
PK Endpoint - AUC(0-10h) at C1D14 [units: ug/mL] Mean (Standard Deviation)	0.1742 (0.06597)	0.2331 (0.04241)	0.1919 (0.09190)	0.2440 (0.07010)	0.1795 (0.06601)	0.1738 (0.1277)	0.1096 (0.04146)	0.1364 (0.4727)

No statistical analysis provided for PK Endpoint - AUC(0-10h) at C1D14

10. Secondary Outcome Measure: PK Endpoint - Cmax at C2D1 [ Time Frame: PK samples were collected at C2D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration. ]

Measure Type	Secondary
Measure Name	PK Endpoint - Cmax at C2D1
Measure Description	Cmax at steady state (Cmax ss) following administration of multiple doses of olaparib (C2D1).
Time Frame	PK samples were collected at C2D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
PK 100 mg	Sub-set of PK population with dose level = 100 mg (regardless of cycle length)
PK 200 mg	Sub-set of PK population with dose level = 200 mg
PK 400 mg	Sub-set of PK population with dose level = 400 mg

Measured Values

	PK 100 mg	PK 200 mg	PK 400 mg
Number of Participants Analyzed [units:participants]	4	25	3
PK Endpoint - Cmax at C2D1 [units: ug/mL] Mean (Standard Deviation)	3.920 (0.8631)	6.118 (4.349)	5.403 (1.120)

No statistical analysis provided for PK Endpoint - Cmax at C2D1

11. Secondary Outcome Measure: PK Endpoint - AUC(0-6h) at C2D1 [ Time Frame: PK samples were collected at C2D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration. ]

Measure Type	Secondary
Measure Name	PK Endpoint - AUC(0-6h) at C2D1
Measure Description	AUC to 6 hours post-dose following administration of multiple doses of olaparib (C2D1).
Time Frame	PK samples were collected at C2D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
PK 100 mg	Sub-set of PK population with dose level = 100 mg (regardless of cycle length)
PK 200 mg	Sub-set of PK population with dose level = 200 mg
PK 400 mg	Sub-set of PK population with dose level = 400 mg

Measured Values

	PK 100 mg	PK 200 mg	PK 400 mg
Number of Participants Analyzed [units:participants]	4	25	3
PK Endpoint - AUC(0-6h) at C2D1 [units: ug/mL] Mean (Standard Deviation)	16.20 (2.936)	26.26 (21.30)	23.59 (8.916)

No statistical analysis provided for PK Endpoint - AUC(0-6h) at C2D1

12. Secondary Outcome Measure: PK Endpoint - tmax at C2D1 [ Time Frame: PK samples were collected at C2D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration. ]

Measure Type	Secondary
Measure Name	PK Endpoint - tmax at C2D1
Measure Description	Time to reach maximum plasma concentration (tmax) at steady state (ss) following administration of multiple doses of olaparib (C2D1).
Time Frame	PK samples were collected at C2D1 pre-drug administration and at 1 (-/+0.5) hour, 2 (-/+1) hours, 4 (-/+1.5) hours, 9 (-/+3) hours post-drug administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
PK 100 mg	Sub-set of PK population with dose level = 100 mg (regardless of cycle length)
PK 200 mg	Sub-set of PK population with dose level = 200 mg
PK 400 mg	Sub-set of PK population with dose level = 400 mg
PK 600 mg	Sub-set of PK population with dose level = 600 mg

Measured Values

	PK 100 mg	PK 200 mg	PK 400 mg	PK 600 mg
Number of Participants Analyzed [units:participants]	4	25	3	2
PK Endpoint - tmax at C2D1 [units: hours] Median (Full Range)	2.25 (1.50 to 3.00)	1.50 (1.50 to 3.00)	1.50 (1.50 to 1.50)	2.25 (1.50 to 3.00)

No statistical analysis provided for PK Endpoint - tmax at C2D1

Serious Adverse Events

Time Frame	Safety data were collected from the time informed consent was given, throughout the treatment period and up to and including the 30 day follow-up period.
Additional Description	The safety and tolerability profile of olaparib was assessed by AEs, laboratory tests, physical examination and vital signs.

Reporting Groups

	Description
<100 mg bd	Pooled dose level of olaparib administered for 14 days, with 21 day cycles, at: - 10 mg once daily (od) - 20 mg od - 40 mg od - 80 mg od - 60 mg twice daily (bd) OR - 100 bd.
100 mg bd	Olaparib 100 mg bd for 28 days with 28 day cycles.
200 mg bd	Olaparib 200 mg bd for 28 days with 28 day cycles.
400 mg bd	Olaparib 400 mg bd for 28 days with 28 day cycles.
600 mg bd	Olaparib 600 mg bd for 28 days with 28 day cycles.
Safety evaluable population	All participants who received any study medication.

Serious Adverse Events

<100 mg bd

100 mg bd

200 mg bd

400 mg bd

600 mg bd

Safety evaluable population

Total, serious adverse events

# participants affected / at risk

5/22 (22.73%)

3/5 (60.00%)

24/58 (41.38%)

7/8 (87.50%)

3/5 (60.00%)

42/98 (42.86%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

5/58 (8.62%)

0/8 (0.00%)

0/5 (0.00%)

5/98 (5.10%)

# events

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

2/58 (3.45%)

1/8 (12.50%)

1/5 (20.00%)

4/98 (4.08%)

# events

Cardiac disorders

Atrial tachycardia¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

2/58 (3.45%)

0/8 (0.00%)

0/5 (0.00%)

2/98 (2.04%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Gastrointestinal disorders

Duodenal obstruction¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Gastrointestinal disorders

Intestinal obstruction¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

3/58 (5.17%)

2/8 (25.00%)

0/5 (0.00%)

6/98 (6.12%)

# events

Gastrointestinal disorders

Large intestinal obstruction¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

1/5 (20.00%)

2/98 (2.04%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

2/98 (2.04%)

# events

General disorders

Disease progression¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

5/58 (8.62%)

0/8 (0.00%)

1/5 (20.00%)

6/98 (6.12%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

2/58 (3.45%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

General disorders

General physical health deterioration¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

General disorders

Pyrexia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Infections and infestations

Central line infection¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

2/58 (3.45%)

1/8 (12.50%)

0/5 (0.00%)

3/98 (3.06%)

# events

Infections and infestations

Infection¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

3/58 (5.17%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Infections and infestations

Neutropenic sepsis¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

2/8 (25.00%)

0/5 (0.00%)

2/98 (2.04%)

# events

Infections and infestations

Streptococcal bacteraemia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

3/98 (3.06%)

# events

Injury, poisoning and procedural complications

Post procedural haemorrhage¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Investigations

Blood amylase increased¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to central nervous system¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Nervous system disorders

Cauda equina syndrome¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Nervous system disorders

Cognitive disorder¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

1/5 (20.00%)

2/98 (2.04%)

# events

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Nervous system disorders

Transient ischaemic attack¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Renal and urinary disorders

Urinary retention¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Renal and urinary disorders

Urinary tract obstruction¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Reproductive system and breast disorders

Female genital tract fistula¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Reproductive system and breast disorders

Vaginal discharge¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

2/58 (3.45%)

0/8 (0.00%)

0/5 (0.00%)

2/98 (2.04%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

2/58 (3.45%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 10.0

Other Adverse Events

Time Frame	Safety data were collected from the time informed consent was given, throughout the treatment period and up to and including the 30 day follow-up period.
Additional Description	The safety and tolerability profile of olaparib was assessed by AEs, laboratory tests, physical examination and vital signs.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
<100 mg bd	Pooled dose level of olaparib administered for 14 days, with 21 day cycles, at: - 10 mg once daily (od) - 20 mg od - 40 mg od - 80 mg od - 60 mg twice daily (bd) OR - 100 bd.
100 mg bd	Olaparib 100 mg bd for 28 days with 28 day cycles.
200 mg bd	Olaparib 200 mg bd for 28 days with 28 day cycles.
400 mg bd	Olaparib 400 mg bd for 28 days with 28 day cycles.
600 mg bd	Olaparib 600 mg bd for 28 days with 28 day cycles.
Safety evaluable population	All participants who received any study medication.

Other Adverse Events

<100 mg bd

100 mg bd

200 mg bd

400 mg bd

600 mg bd

Safety evaluable population

Total, other (not including serious) adverse events

# participants affected / at risk

22/22 (100.00%)

5/5 (100.00%)

58/58 (100.00%)

8/8 (100.00%)

5/5 (100.00%)

98/98 (100.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

6/22 (27.27%)

1/5 (20.00%)

14/58 (24.14%)

3/8 (37.50%)

2/5 (40.00%)

26/98 (26.53%)

# events

Blood and lymphatic system disorders

Lymphopenia¹,^†

# participants affected / at risk

1/22 (4.55%)

1/5 (20.00%)

10/58 (17.24%)

1/8 (12.50%)

1/5 (20.00%)

14/98 (14.29%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

3/58 (5.17%)

0/8 (0.00%)

1/5 (20.00%)

4/98 (4.08%)

# events

Cardiac disorders

Tachycardia¹,^†

# participants affected / at risk

11/22 (50.00%)

1/5 (20.00%)

20/58 (34.48%)

2/8 (25.00%)

2/5 (40.00%)

36/98 (36.73%)

# events

Ear and labyrinth disorders

Cerumen impaction¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Ear and labyrinth disorders

Tinnitus¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

2/98 (2.04%)

# events

Gastrointestinal disorders

Abdominal discomfort¹,^†

# participants affected / at risk

3/22 (13.64%)

0/5 (0.00%)

3/58 (5.17%)

1/8 (12.50%)

0/5 (0.00%)

7/98 (7.14%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

5/58 (8.62%)

0/8 (0.00%)

0/5 (0.00%)

6/98 (6.12%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

1/22 (4.55%)

2/5 (40.00%)

12/58 (20.69%)

2/8 (25.00%)

0/5 (0.00%)

17/98 (17.35%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

8/58 (13.79%)

0/8 (0.00%)

0/5 (0.00%)

10/98 (10.20%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

4/22 (18.18%)

1/5 (20.00%)

12/58 (20.69%)

1/8 (12.50%)

0/5 (0.00%)

18/98 (18.37%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

5/22 (22.73%)

1/5 (20.00%)

17/58 (29.31%)

1/8 (12.50%)

2/5 (40.00%)

26/98 (26.53%)

# events

Gastrointestinal disorders

Dry mouth¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

2/58 (3.45%)

2/8 (25.00%)

1/5 (20.00%)

6/98 (6.12%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

12/58 (20.69%)

0/8 (0.00%)

2/5 (40.00%)

15/98 (15.31%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

14/22 (63.64%)

2/5 (40.00%)

36/58 (62.07%)

1/8 (12.50%)

4/5 (80.00%)

57/98 (58.16%)

# events

Gastrointestinal disorders

Proctalgia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

2/98 (2.04%)

# events

Gastrointestinal disorders

Rectal hemorrhage¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Gastrointestinal disorders

Reflux oesophagitis¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

4/58 (6.90%)

0/8 (0.00%)

0/5 (0.00%)

5/98 (5.10%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

10/22 (45.45%)

2/5 (40.00%)

28/58 (48.28%)

2/8 (25.00%)

3/5 (60.00%)

45/98 (45.92%)

# events

General disorders

Chest discomfort¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

1/5 (20.00%)

3/98 (3.06%)

# events

General disorders

Disease progression¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

1/5 (20.00%)

4/98 (4.08%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

9/22 (40.91%)

2/5 (40.00%)

31/58 (53.45%)

5/8 (62.50%)

4/5 (80.00%)

51/98 (52.04%)

# events

General disorders

Feeling cold¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

General disorders

Influenza like illness¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

6/58 (10.34%)

0/8 (0.00%)

0/5 (0.00%)

7/98 (7.14%)

# events

General disorders

Malaise¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

3/58 (5.17%)

0/8 (0.00%)

0/5 (0.00%)

4/98 (4.08%)

# events

General disorders

Oedema peripheral¹,^†

# participants affected / at risk

3/22 (13.64%)

2/5 (40.00%)

10/58 (17.24%)

1/8 (12.50%)

1/5 (20.00%)

17/98 (17.35%)

# events

General disorders

Pyrexia¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

6/58 (10.34%)

0/8 (0.00%)

1/5 (20.00%)

8/98 (8.16%)

# events

Infections and infestations

Candidiasis¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

5/58 (8.62%)

0/8 (0.00%)

1/5 (20.00%)

6/98 (6.12%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

7/58 (12.07%)

0/8 (0.00%)

1/5 (20.00%)

10/98 (10.20%)

# events

Infections and infestations

Oral candidiasis¹,^†

# participants affected / at risk

1/22 (4.55%)

1/5 (20.00%)

4/58 (6.90%)

1/8 (12.50%)

1/5 (20.00%)

8/98 (8.16%)

# events

Infections and infestations

Oral herpes¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

2/98 (2.04%)

# events

Infections and infestations

Otitis externa¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

6/58 (10.34%)

1/8 (12.50%)

0/5 (0.00%)

7/98 (7.14%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

3/22 (13.64%)

0/5 (0.00%)

6/58 (10.34%)

2/8 (25.00%)

0/5 (0.00%)

11/98 (11.22%)

# events

Infections and infestations

Vaginal candidiasis¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

2/8 (25.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Injury, poisoning and procedural complications

Procedural pain¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

1/5 (20.00%)

2/98 (2.04%)

# events

Injury, poisoning and procedural complications

Skeletal injury¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Investigations

Activated partial thromboplastin time prolonged¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

2/58 (3.45%)

1/8 (12.50%)

1/5 (20.00%)

5/98 (5.10%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

1/8 (12.50%)

1/5 (20.00%)

3/98 (3.06%)

# events

Investigations

Blood alkaline phosphatase increased¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

1/5 (20.00%)

3/98 (3.06%)

# events

Investigations

Blood amylase increased¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

1/5 (20.00%)

2/98 (2.04%)

# events

Investigations

Blood uric acid increased¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

2/98 (2.04%)

# events

Investigations

Haemoglobin decreased¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Investigations

Prothrombin time prolonged¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

6/22 (27.27%)

1/5 (20.00%)

15/58 (25.86%)

1/8 (12.50%)

1/5 (20.00%)

24/98 (24.49%)

# events

Investigations

Weight increased¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

4/58 (6.90%)

1/8 (12.50%)

0/5 (0.00%)

6/98 (6.12%)

# events

Metabolism and nutrition disorders

Anorexia¹,^†

# participants affected / at risk

9/22 (40.91%)

1/5 (20.00%)

16/58 (27.59%)

1/8 (12.50%)

3/5 (60.00%)

30/98 (30.61%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

2/98 (2.04%)

# events

Metabolism and nutrition disorders

Hypoalbuminaemia¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

2/58 (3.45%)

2/8 (25.00%)

0/5 (0.00%)

5/98 (5.10%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

5/58 (8.62%)

0/8 (0.00%)

0/5 (0.00%)

6/98 (6.12%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

4/58 (6.90%)

0/8 (0.00%)

1/5 (20.00%)

5/98 (5.10%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

3/22 (13.64%)

0/5 (0.00%)

4/58 (6.90%)

1/8 (12.50%)

1/5 (20.00%)

9/98 (9.18%)

# events

Metabolism and nutrition disorders

Hypophosphataemia¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

3/98 (3.06%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

4/58 (6.90%)

1/8 (12.50%)

1/5 (20.00%)

7/98 (7.14%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

3/22 (13.64%)

1/5 (20.00%)

8/58 (13.79%)

1/8 (12.50%)

1/5 (20.00%)

14/98 (14.29%)

# events

Musculoskeletal and connective tissue disorders

Bone pain¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

4/58 (6.90%)

0/8 (0.00%)

0/5 (0.00%)

5/98 (5.10%)

# events

Musculoskeletal and connective tissue disorders

Flank pain¹,^†

# participants affected / at risk

1/22 (4.55%)

1/5 (20.00%)

3/58 (5.17%)

0/8 (0.00%)

0/5 (0.00%)

5/98 (5.10%)

# events

Musculoskeletal and connective tissue disorders

Groin pain¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

4/58 (6.90%)

0/8 (0.00%)

0/5 (0.00%)

5/98 (5.10%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

1/5 (20.00%)

2/98 (2.04%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

1/22 (4.55%)

1/5 (20.00%)

5/58 (8.62%)

1/8 (12.50%)

0/5 (0.00%)

8/98 (8.16%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

3/58 (5.17%)

2/8 (25.00%)

1/5 (20.00%)

7/98 (7.14%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour pain¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

2/58 (3.45%)

0/8 (0.00%)

1/5 (20.00%)

3/98 (3.06%)

# events

Nervous system disorders

Cognitive disorder¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

2/98 (2.04%)

# events

Nervous system disorders

Disturbance in attention¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

3/98 (3.06%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

6/58 (10.34%)

3/8 (37.50%)

0/5 (0.00%)

10/98 (10.20%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

7/58 (12.07%)

1/8 (12.50%)

3/5 (60.00%)

13/98 (13.27%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

3/22 (13.64%)

0/5 (0.00%)

13/58 (22.41%)

0/8 (0.00%)

0/5 (0.00%)

16/98 (16.33%)

# events

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

3/58 (5.17%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

4/58 (6.90%)

0/8 (0.00%)

0/5 (0.00%)

4/98 (4.08%)

# events

Nervous system disorders

Peripheral sensory neuropathy¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

4/58 (6.90%)

0/8 (0.00%)

0/5 (0.00%)

4/98 (4.08%)

# events

Nervous system disorders

Sciatica¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

3/98 (3.06%)

# events

Nervous system disorders

Tremor¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

1/22 (4.55%)

1/5 (20.00%)

4/58 (6.90%)

1/8 (12.50%)

2/5 (40.00%)

9/98 (9.18%)

# events

Psychiatric disorders

Depressed mood¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

2/98 (2.04%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

3/58 (5.17%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Psychiatric disorders

Hallucination¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

1/5 (20.00%)

2/98 (2.04%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

4/58 (6.90%)

0/8 (0.00%)

0/5 (0.00%)

4/98 (4.08%)

# events

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Renal and urinary disorders

Ureteric obstruction¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Renal and urinary disorders

Urinary tract obstruction¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Reproductive system and breast disorders

Pelvic pain¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

3/58 (5.17%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Reproductive system and breast disorders

Vaginal haemorrhage¹,^†

# participants affected / at risk

0/22 (0.00%)

1/5 (20.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

1/98 (1.02%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

5/22 (22.73%)

0/5 (0.00%)

4/58 (6.90%)

1/8 (12.50%)

0/5 (0.00%)

10/98 (10.20%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

4/22 (18.18%)

0/5 (0.00%)

9/58 (15.52%)

1/8 (12.50%)

1/5 (20.00%)

15/98 (15.31%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

0/5 (0.00%)

2/98 (2.04%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

2/58 (3.45%)

0/8 (0.00%)

0/5 (0.00%)

4/98 (4.08%)

# events

Respiratory, thoracic and mediastinal disorders

Pharyngolaryngeal pain¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

2/58 (3.45%)

0/8 (0.00%)

0/5 (0.00%)

4/98 (4.08%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

3/58 (5.17%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

3/58 (5.17%)

0/8 (0.00%)

0/5 (0.00%)

5/98 (5.10%)

# events

Skin and subcutaneous tissue disorders

Erythema¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Skin and subcutaneous tissue disorders

Hyperhidrosis¹,^†

# participants affected / at risk

3/22 (13.64%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

4/98 (4.08%)

# events

Skin and subcutaneous tissue disorders

Night sweats¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

2/98 (2.04%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

1/58 (1.72%)

1/8 (12.50%)

0/5 (0.00%)

3/98 (3.06%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

4/58 (6.90%)

1/8 (12.50%)

0/5 (0.00%)

6/98 (6.12%)

# events

Skin and subcutaneous tissue disorders

Skin discomfort¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Skin and subcutaneous tissue disorders

Skin ulcer¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

1/8 (12.50%)

0/5 (0.00%)

1/98 (1.02%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

1/58 (1.72%)

0/8 (0.00%)

0/5 (0.00%)

3/98 (3.06%)

# events

Vascular disorders

Extremity necrosis¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

1/22 (4.55%)

0/5 (0.00%)

5/58 (8.62%)

2/8 (25.00%)

0/5 (0.00%)

8/98 (8.16%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

2/22 (9.09%)

0/5 (0.00%)

0/58 (0.00%)

2/8 (25.00%)

0/5 (0.00%)

4/98 (4.08%)

# events

Vascular disorders

Peripheral ischaemia¹,^†

# participants affected / at risk

0/22 (0.00%)

0/5 (0.00%)

0/58 (0.00%)

0/8 (0.00%)

1/5 (20.00%)

1/98 (1.02%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 10.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
N/A

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
CSR_Synopsis_D0810C00002(KU36-92).pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Jane Robertson

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

CSR_Synopsis_D0810C00002(KU36-92).pdf

Trial Results Summaries