A 4 Week Study to Investigate the Safety and Tolerability of AZD5069 in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) - CIRRUS

Study identifier:D3550C00002

ClinicalTrials.gov identifier:N/A

EudraCT identifier:2010-021217-23

CTIS identifier:N/A

Study Complete

Official Title

A 4 Week, Double Blind, Placebo Controlled, Randomised, Parallel Group, Multicentre, Phase IIa Study to Investigate the Safety and Tolerability of AZD5069 as Oral Capsules in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease

Medical condition

Scientific Terminology Chronic Obstructive Pulmonary Disease (COPD)

Phase

Phase 2

Healthy volunteers

Study drug

Placebo, AZD5069 50mg, AZD5069 80mg

Sex

All

Actual Enrollment

109

Study type

Interventional

Age

40 Years - 80 Years

Date

Study Start Date: 01 Nov 2010

Primary Completion Date: 01 Mar 2011

Study Completion Date: 01 Mar 2011

Study design

Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2015 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

SOFIA, Bulgaria

Location

Research Site

BERLIN, Germany

Location

Research Site

GROßHANSDORF, Germany

Location

Research Site

DEBRECEN, Hungary

Location

Research Site

PÉCS, Hungary

Location

Research Site

SZÁZHALOMBATTA, Hungary

Location

Research Site

SZEGED, Hungary

Location

Research Site

KYIV, Ukraine

Arms	Assigned Interventions
Placebo Comparator: 1 Placebo dose	Drug: Placebo Oral dose bid
Experimental: 2 Treatment arm AZD5069 50mg	Drug: AZD5069 50mg Oral dose bid
Experimental: 3 Treatment arm AZD5069 80mg	Drug: AZD5069 80mg Oral dose bid

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 patient enrolled: 22 November 2010. Last patient completed: 22 March 2011. Fifteen centres across 4 countries participated in this study: Bulgaria (4), Germany (4), Hungary (4) and Ukraine (3)

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
22 patients enrolled were not randomized due to eligibility not fulfilled (17 patients) and voluntary discontinuation (5 patients)

Reporting Groups

	Description
Placebo	4 x placebo capsules, twice daily (bid)
AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Participant Flow: Overall Study

	Placebo	AZD5069 50 mg	AZD5069 80 mg
STARTED	29	30	28
COMPLETED	28	30	28
NOT COMPLETED	1	0	0
Voluntary Discontinuation by Subject	1	0	0

Baseline Characteristics

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

Reporting Groups

	Description
Placebo	4 x placebo capsules, twice daily (bid)
AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Baseline Measures

	Placebo	AZD5069 50 mg	AZD5069 80 mg	Total
Number of Participants [units: Participants]	29	30	28	87
Age Continuous [units: Years] Mean ± Standard Deviation	62 ± 7.9	65 ± 6.9	65 ± 7.4	64 ± 7.4
Gender, Male/Female [units: Participants]
Female	9	12	6	27
Male	20	18	22	60
Body Mass Index [units: kg/m^2] Mean ± Standard Deviation	24.842 ± 2.77	27.645 ± 2.89	25.803 ± 3.18	26.118 ± 3.14
Weight [units: Kg] Mean ± Standard Deviation	73.7 ± 14.02	78.9 ± 9.18	75.4 ± 10.90	76 ± 11.59
% Predicted FEV1 at screening [units: %] Mean ± Standard Deviation	56 ± 13.9	57 ± 13.6	54 ± 12.1	56 ± 13.2
FEV1/FVC at screening [units: %] Mean ± Standard Deviation	52.54 ± 9.62	51.75 ± 11.65	54.52 ± 10.51	52.91 ± 10.58
Nicotine pack years ^[1] [units: Pack Year] Mean ± Standard Deviation	38 ± 21.4	39 ± 22	34 ± 17.9	37 ± 20.4
GOLD classification ^[2] [units: Participants]
II Moderate	17	20	16	53
III Severe	12	10	12	34

Outcome Measures

1. Primary Outcome Measure: Patients Who Experienced at Least One Adverse Events(s) [ Time Frame: From start of treatment (Day 0) up to 28 days (End of Treatment) ]

Measure Type	Primary
Measure Name	Patients Who Experienced at Least One Adverse Events(s)
Measure Description	Adverse event (AE) data, both serious and non-serious. An AE is the development of an undesirable medical condition (eg, nausea, chest pain, tachycardia, laboratory findings) or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Time Frame	From start of treatment (Day 0) up to 28 days (End of Treatment)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	29	30	28
Patients Who Experienced at Least One Adverse Events(s) [units: Participants]	9	10	6

No statistical analysis provided for Patients Who Experienced at Least One Adverse Events(s)

2. Primary Outcome Measure: Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Last Observation on Treatment (up to Day 28) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Physical Examination Findings
Measure Description	Physical examination includes assessment of general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, musculo-skeletal (including spine and extremities), cardiovascular, lungs and abdomen. The findings were deemed to be normal/abnormal based on the clinical judgment of the investigator.
Time Frame	Last Observation on Treatment (up to Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	29	30	28
Number of Participants With Abnormal Physical Examination Findings [units: Participants]	0	0	1

No statistical analysis provided for Number of Participants With Abnormal Physical Examination Findings

3. Primary Outcome Measure: Number of Participants With Abnormal Electrocardiogram (ECG) [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Electrocardiogram (ECG)
Measure Description	ECGs were recorded in the supine position after the patient has rested for 10 minutes. Heart rate, QRS duration, PR, RR and QT intervals were recorded. Overall evaluation of the ECG is classified as normal, abnormal or borderline. Only participants with ECG at baseline classified as normal are reported (ie, only changes from normal to abnormal).
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	22	25	23
Number of Participants With Abnormal Electrocardiogram (ECG) [units: Participants]	0	0	0

No statistical analysis provided for Number of Participants With Abnormal Electrocardiogram (ECG)

4. Primary Outcome Measure: Change from Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample) [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Change from Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample)
Measure Description	The change in circulating leucocyte counts (including neutrophils) is calculated as the End of Treatment value minus the Baseline value.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	28	28	28
Change from Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample) [units: 10^9/L cells/L] Mean (Standard Deviation)	-0.12 (1.974)	-1.55 (2.059)	-1.08 (2.404)

No statistical analysis provided for Change from Baseline to End of Treatment for Leucocytes Count in Blood (Safety Blood Sample)

5. Primary Outcome Measure: Change from Baseline to End of Treatment for Body Temperature [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Change from Baseline to End of Treatment for Body Temperature
Measure Description	The change in body temperature (oral) is calculated as the End of Treatment value minus the Baseline value.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	28	30	28
Change from Baseline to End of Treatment for Body Temperature [units: degrees C] Mean (Standard Deviation)	-0.1 (0.43)	0.0 (0.57)	-0.0 (0.39)

No statistical analysis provided for Change from Baseline to End of Treatment for Body Temperature

6. Primary Outcome Measure: Change from Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs) [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Change from Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs)
Measure Description	The change in systolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	28	30	28
Change from Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs) [units: mmHg] Mean (Standard Deviation)	3.0 (11.0)	-0.0 (12.1)	-3.0 (15.7)

No statistical analysis provided for Change from Baseline to End of Treatment for Systolic Blood Preassure (Vital Signs)

7. Primary Outcome Measure: Change from Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs) [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Change from Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs)
Measure Description	The change in diastolic blood pressure (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	28	30	28
Change from Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs) [units: mmHg] Mean (Standard Deviation)	2.0 (7.2)	-2.0 (7.9)	-1.0 (8.2)

No statistical analysis provided for Change from Baseline to End of Treatment for Diastolic Blood Pressure (Vital Signs)

8. Primary Outcome Measure: Change from Baseline to End of Treatment for Pulse Rate (Vital Signs) [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Change from Baseline to End of Treatment for Pulse Rate (Vital Signs)
Measure Description	The change in pulse rate (Vital Sign) is calculated as the End of Treatment value minus the Baseline value.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	28	30	28
Change from Baseline to End of Treatment for Pulse Rate (Vital Signs) [units: beats/minute] Mean (Standard Deviation)	1 (6.2)	-1 (6.9)	3 (7.9)

No statistical analysis provided for Change from Baseline to End of Treatment for Pulse Rate (Vital Signs)

9. Primary Outcome Measure: Change from Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test) [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Change from Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test)
Measure Description	The change in FEV1 Pre-bronchodilator is calculated as the End of Treatment value minus the Baseline value.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	28	30	27
Change from Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test) [units: L] Mean (Standard Deviation)	-0.03 (0.238)	0.05 (0.238)	-0.01 (0.218)

No statistical analysis provided for Change from Baseline to End of Treatment for FEV1 Pre-bronchodilator (Lung Function Test)

10. Primary Outcome Measure: Change from Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test) [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Change from Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test)
Measure Description	The change in FEV1 Post-bronchodilator is calculated as the End of Treatment value minus the Baseline value.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	27	30	28
Change from Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test) [units: L] Mean (Standard Deviation)	-0.02 (0.230)	0.10 (0.256)	0.02 (0.194)

No statistical analysis provided for Change from Baseline to End of Treatment for FEV1 Post-bronchodilator (Lung Function Test)

11. Primary Outcome Measure: Number of Participants Who Developed High Transaminase Values (Clinical Chemistry) [ Time Frame: Up to Follow-up Visit (3 to 18 days after End of Treatment [Day 28]) ]

Measure Type	Primary
Measure Name	Number of Participants Who Developed High Transaminase Values (Clinical Chemistry)
Measure Description	High Transaminase Values are defined as a measurment of ALT (alanine aminotransferase) or AST (aspartate aminotransferase) greater than or equal to 3 times the upper limit of normal (ALT ULN = 36 IU/L, AST ULN = 33 IU/L).
Time Frame	Up to Follow-up Visit (3 to 18 days after End of Treatment [Day 28])
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	29	30	28
Number of Participants Who Developed High Transaminase Values (Clinical Chemistry) [units: Participants]	0	0	0

No statistical analysis provided for Number of Participants Who Developed High Transaminase Values (Clinical Chemistry)

12. Primary Outcome Measure: Change from Baseline to End of Treatment for Total Protein (Urinalysis) [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28) ]

Measure Type	Primary
Measure Name	Change from Baseline to End of Treatment for Total Protein (Urinalysis)
Measure Description	The change in total protein in urine is calculated as the End of Treatment value minus the Baseline value.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication) and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	6	4	1
Change from Baseline to End of Treatment for Total Protein (Urinalysis) [units: g/L] Mean (Standard Deviation)	-0.02 (0.034)	-0.01 (0.022)	-0.01 (NA)^[1]

No statistical analysis provided for Change from Baseline to End of Treatment for Total Protein (Urinalysis)

13. Secondary Outcome Measure: Plasma concentration of AZD5069 after 1 hour of dosing [ Time Frame: End of Treatment (Day 28), 1 hour after dosing ]

Measure Type	Secondary
Measure Name	Plasma concentration of AZD5069 after 1 hour of dosing
Measure Description	At this visit, approximately 1 hour after dosing (at the clinic), a blood sample was collected for determination of drug concentration in plasma.
Time Frame	End of Treatment (Day 28), 1 hour after dosing
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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	0	18	18
Plasma concentration of AZD5069 after 1 hour of dosing [units: nmol/L] Mean (Standard Deviation)		2599.551 (2085.601)	5433.611 (4622.932)

No statistical analysis provided for Plasma concentration of AZD5069 after 1 hour of dosing

14. Secondary Outcome Measure: Area Under the Plasma Concentration Curve of AZD5069 [ Time Frame: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing ]

Measure Type	Secondary
Measure Name	Area Under the Plasma Concentration Curve of AZD5069
Measure Description	The area under the plasma concentration curve is estimated from time 0 (dosing) to 24 hours after dosing.
Time Frame	End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
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
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	26	22
Area Under the Plasma Concentration Curve of AZD5069 [units: nmol*h/L] Geometric Mean (Geometric Coefficient of Variation)	29600 (108%)	38800 (95.6%)

No statistical analysis provided for Area Under the Plasma Concentration Curve of AZD5069

15. Secondary Outcome Measure: Maximum Plasma Concentration for AZD5069 [ Time Frame: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing ]

Measure Type	Secondary
Measure Name	Maximum Plasma Concentration for AZD5069
Measure Description	The maximum plasma concentration (Cmax) is the highest level of drug in plasma.
Time Frame	End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
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
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	26	22
Maximum Plasma Concentration for AZD5069 [units: nmol/L] Geometric Mean (Geometric Coefficient of Variation)	2550 (107%)	3340 (95.6%)

No statistical analysis provided for Maximum Plasma Concentration for AZD5069

16. Secondary Outcome Measure: Time to Maximum Plasma Concentration for AZD5069 [ Time Frame: End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing ]

Measure Type	Secondary
Measure Name	Time to Maximum Plasma Concentration for AZD5069
Measure Description	Time (in relation to dosing) at which the maximum plasma concentration is observed.
Time Frame	End of Treatment (Day 28); pre-dose, 1, 2, 3, and 5 hours after dosing
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
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	26	22
Time to Maximum Plasma Concentration for AZD5069 [units: hours] Median (Inter-Quartile Range)	1.56 (1.56 to 1.56)	1.56 (1.56 to 1.56)

No statistical analysis provided for Time to Maximum Plasma Concentration for AZD5069

17. Secondary Outcome Measure: Maximum reduction of Circulating Neutrophils in Blood, from Baseline [ Time Frame: Baseline (last non-missing assessment prior to first dose of study medication), weeks 1, 2 and 3, and End of Treatment (Day 28) ]

Measure Type	Secondary
Measure Name	Maximum reduction of Circulating Neutrophils in Blood, from Baseline
Measure Description	The change in circulating neutrophils in blood is calculated as the visit value minus the Baseline value. Only participants with reduction are considered.
Time Frame	Baseline (last non-missing assessment prior to first dose of study medication), weeks 1, 2 and 3, and End of Treatment (Day 28)
Safety Issue?	Yes

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
Arm 1 - Placebo	4 x placebo capsules, twice daily (bid)
Arm 2 - AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
Arm 3 - AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Measured Values

	Arm 1 - Placebo	Arm 2 - AZD5069 50 mg	Arm 3 - AZD5069 80 mg
Number of Participants Analyzed [units:participants]	22	30	26
Maximum reduction of Circulating Neutrophils in Blood, from Baseline [units: 10^9/L cells/L] Mean (Standard Deviation)	1.324 (1.2152)	2.759 (1.4422)	2.678 (2.0710)

No statistical analysis provided for Maximum reduction of Circulating Neutrophils in Blood, from Baseline

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Placebo	4 x placebo capsules, twice daily (bid)
AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Serious Adverse Events

Placebo

AZD5069 50 mg

AZD5069 80 mg

Total, serious adverse events

# participants affected / at risk

0/29 (0.00%)

1/30 (3.33%)

1/28 (3.57%)

Cardiac disorders

Atrial Fibrillation¹

# participants affected / at risk

0/29 (0.00%)

1/30 (3.33%)

0/28 (0.00%)

Respiratory, thoracic and mediastinal disorders

Chronic Obstructive Pulmonary Disease¹,^†

# participants affected / at risk

0/29 (0.00%)

0/30 (0.00%)

1/28 (3.57%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	4%

Reporting Groups

	Description
Placebo	4 x placebo capsules, twice daily (bid)
AZD5069 50 mg	1 x 50 mg AZD5069 capsule and 3 x placebo capsules, bid
AZD5069 80 mg	4 x 20 AZD5069 mg capsules, bid

Other Adverse Events

Placebo

AZD5069 50 mg

AZD5069 80 mg

Total, other (not including serious) adverse events

# participants affected / at risk

3/29 (10.34%)

8/30 (26.67%)

1/28 (3.57%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

2/29 (6.90%)

4/30 (13.33%)

0/28 (0.00%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/29 (3.45%)

2/30 (6.67%)

0/28 (0.00%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

2/29 (6.90%)

1/30 (3.33%)

0/28 (0.00%)

Investigations

Neutrophil Count Decreased¹,^†

# participants affected / at risk

0/29 (0.00%)

3/30 (10.00%)

1/28 (3.57%)

Respiratory, thoracic and mediastinal disorders

Chronic Obstructive Pulmonary Disease¹,^†

# participants affected / at risk

0/29 (0.00%)

2/30 (6.67%)

1/28 (3.57%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.1
2	Term from vocabulary,

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
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

D3550C00002_Revised_Clinical_Study_Protocol.pdf
Download
D3550C00002_Study_Synopsis.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-2369933

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

D3550C00002_Revised_Clinical_Study_Protocol.pdf

D3550C00002_Study_Synopsis.pdf

Trial Results Summaries