AZD2066 Neuropathic pain - Mechanical Hypersensitivity - NP-MH

Study identifier:D0475C00016

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase IIa, Double-Blind, Randomised, Parallel-Group, Multi-Centre Study to Evaluate the Analgesic Efficacy of 28 Days Oral Administration of AZD2066 Compared to Placebo in Peripheral Neuropathic Pain Patients with Mechanical Hypersensitivity

Medical condition

Neuropathic Pain

Phase

Phase 2

Healthy volunteers

Study drug

AZD2066, Placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 80 Years

Date

Study Start Date: 01 Aug 2009

Primary Completion Date: 01 Nov 2010

Study Completion Date: 01 Nov 2010

Study design

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

Verification:

Verified 01 Aug 2012 by AstraZeneca Pharmaceuticals

Collaborators

Quintiles, Inc.

Inclusion and exclusion criteria

Location

Research Site

TUCSON, AZ, United States

Location

Research Site

LOS ANGELES, CA, United States

Location

Research Site

SACRAMENTO, CA, United States

Location

Research Site

SAN FRANCISCO, CA, United States

Location

Research Site

WALNUT CREEK, CA, United States

Location

Research Site

BOULDER, CO, United States

Location

Research Site

ATLANTIS, FL, United States

Location

Research Site

AVENTURA, FL, United States

Arms	Assigned Interventions
Experimental: A	Drug: AZD2066 Capsule, once daily
Placebo Comparator: B	Drug: Placebo Capsule, once daily

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This multicenter study was conducted between August 2009 and November 2010 in the United States.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study had an enrolment phase of up to 35 days (including washout and baseline periods), a 28-day treatment phase, and a follow-up phase of 7 days (for men and women not of childbearing potential) or 28 days (for women of childbearing potential). Patients randomized to AZD2066 received AZD2066 12 mg from Days 1 to 4 and 18 mg from Days 5 to 28.

Reporting Groups

	Description
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Participant Flow: Overall Study

	A - AZD2066	2 - Placebo
STARTED	42	45
COMPLETED	28	35
NOT COMPLETED	14	10
Adverse Event	9	0
Withdrawal by Subject	1	6
Lost to Follow-up	1	1
Eligibility criteria not fulfilled	2	0
Severe non-compliance to protocol	0	1
Study stopped by sponsor	0	2
Abnormal ECG findings	1	0

Baseline Characteristics

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

Reporting Groups

	Description
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Baseline Measures

	A - AZD2066	2 - Placebo	Total
Number of Participants [units: Participants]	42	45	87
Age Continuous [units: years] Mean ± Standard Deviation	58.1 ± 9.25	59.3 ± 14.31	58.7 ± 12.8
Gender, Male/Female [units: participants]
Female	24	18	42
Male	18	27	45

Outcome Measures

1. Primary Outcome Measure: Change in mean numerical rating scale (NRS) pain score from baseline to last 5 days on treatment [ Time Frame: Change in mean pain intensity from 5-day baseline to the last 5 days on treatment, measure twice daily with NRS (12-hour recall) ]

Measure Type	Primary
Measure Name	Change in mean numerical rating scale (NRS) pain score from baseline to last 5 days on treatment
Measure Description	Mean pain intensity for 5-day baseline period (morning Day -5 to evening Day-1) and mean pain intensity for last 5 days on treatment (ie, last dose day and the 4 preceding calendar days) was calculated based on the NRS scale (0-10). 0=No pain, 10=Worst pain imaginable.
Time Frame	Change in mean pain intensity from 5-day baseline to the last 5 days on treatment, measure twice daily with NRS (12-hour recall)
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
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Measured Values

	A - AZD2066	2 - Placebo
Number of Participants Analyzed [units:participants]	30	38
Change in mean numerical rating scale (NRS) pain score from baseline to last 5 days on treatment [units: Scores (units) on NRS] Least Squares Mean (Standard Error)	-2.14 (0.358)	-1.26 (0.337)

No statistical analysis provided for Change in mean numerical rating scale (NRS) pain score from baseline to last 5 days on treatment

2. Secondary Outcome Measure: Patients with ≥30% reduction from baseline in NRS pain intensity score (responder rate) at Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Patients with ≥30% reduction from baseline in NRS pain intensity score (responder rate) at Day 28
Measure Description	NRS pain intensity score reduction=(change from baseline at Day 28/baseline)100 Responder=pain intensity score reduction ≥30% (yes/no)? Responder rate=(no. of responders/total no. of patients)100
Time Frame	28 days
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
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Measured Values

	A - AZD2066	2 - Placebo
Number of Participants Analyzed [units:participants]	30	38
Patients with ≥30% reduction from baseline in NRS pain intensity score (responder rate) at Day 28 [units: Participants]	16	10

No statistical analysis provided for Patients with ≥30% reduction from baseline in NRS pain intensity score (responder rate) at Day 28

3. Secondary Outcome Measure: Patients with ≥50% reduction from baseline in NRS pain intensity score (responder rate) at Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Patients with ≥50% reduction from baseline in NRS pain intensity score (responder rate) at Day 28
Measure Description	Pain intensity score reduction=(change from baseline Day 28/baseline)100 Responder=pain intensity score reduction ≥50% (Yes/No)? Responder rate=(no. of responders/total no. of patients)100
Time Frame	28 days
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
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Measured Values

	A - AZD2066	2 - Placebo
Number of Participants Analyzed [units:participants]	30	38
Patients with ≥50% reduction from baseline in NRS pain intensity score (responder rate) at Day 28 [units: Participants]	10	5

No statistical analysis provided for Patients with ≥50% reduction from baseline in NRS pain intensity score (responder rate) at Day 28

4. Secondary Outcome Measure: Patients with Patient Global Impression of Change (PGIC) score of at least “much improved” (responder rate) at Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Patients with Patient Global Impression of Change (PGIC) score of at least “much improved” (responder rate) at Day 28
Measure Description	PGIC scale ranges from 1-7 where 1=Very much improved and 7=Very much worse Responder=Patient with a response of " much improved" or "very much improved" Responder rate=(no. of responders/total no. of patients)*100
Time Frame	28 days
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
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Measured Values

	A - AZD2066	2 - Placebo
Number of Participants Analyzed [units:participants]	30	38
Patients with Patient Global Impression of Change (PGIC) score of at least “much improved” (responder rate) at Day 28 [units: Patients]	10	10

No statistical analysis provided for Patients with Patient Global Impression of Change (PGIC) score of at least “much improved” (responder rate) at Day 28

5. Secondary Outcome Measure: Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index from baseline to Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index from baseline to Day 28
Measure Description	Sensory index=sum of the intensity scale values of the words chosen for the descriptors 1-11 in the questionnaire. Range of scores for the sensory index=0-33 (higher score represents a worse condition). Change from baseline (measured prior to randomization) to Day 28 was calculated.
Time Frame	28 days
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
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Measured Values

	A - AZD2066	2 - Placebo
Number of Participants Analyzed [units:participants]	30	38
Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index from baseline to Day 28 [units: Scores (units) on SF-MPQ Sensory Index] Least Squares Mean (Standard Error)	-6.39 (1.278)	-3.98 (1.188)

No statistical analysis provided for Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index from baseline to Day 28

6. Secondary Outcome Measure: Change in SF-MPQ Affective Index from baseline to Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Change in SF-MPQ Affective Index from baseline to Day 28
Measure Description	Affective index=sum of the intensity scale values of the words chosen for the descriptors 12-15 in the questionnaire. Range of scores for the affective index=0-12 (higher score represents a worse condition). Change from baseline (measured prior to randomization) to Day 28 was calculated.
Time Frame	28 days
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
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Measured Values

	A - AZD2066	2 - Placebo
Number of Participants Analyzed [units:participants]	30	38
Change in SF-MPQ Affective Index from baseline to Day 28 [units: Scores (units) on SF-MPQ Affective Index] Least Squares Mean (Standard Deviation)	-1.1 (0.52)	-0.9 (0.50)

No statistical analysis provided for Change in SF-MPQ Affective Index from baseline to Day 28

7. Secondary Outcome Measure: Change in Brief Pain Inventory-Short Form (BPI-SF) pain severity from baseline to Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Change in Brief Pain Inventory-Short Form (BPI-SF) pain severity from baseline to Day 28
Measure Description	Change from baseline (measured prior to randomization) to Day 28 was calculated for the pain severity (mean of 4 intensity items). Each intensity item is recorded on a NRS 0-10, where 0=No Pain and 10=Pain as bad as you can imagine.
Time Frame	28 days
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
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Measured Values

	A - AZD2066	2 - Placebo
Number of Participants Analyzed [units:participants]	30	38
Change in Brief Pain Inventory-Short Form (BPI-SF) pain severity from baseline to Day 28 [units: Scores (units) on BPI-SF pain severity] Least Squares Mean (Standard Error)	-2.12 (0.385)	-1.25 (0.360)

No statistical analysis provided for Change in Brief Pain Inventory-Short Form (BPI-SF) pain severity from baseline to Day 28

8. Secondary Outcome Measure: Change in BPI-SF pain interference from baseline to Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Change in BPI-SF pain interference from baseline to Day 28
Measure Description	Change from baseline (measured prior to randomization) to Day 28 was calculated for pain interference (mean of 7 interference items). Each interference item is recorded on a NRS 0-10, where 0=No interference and 10=Interferes completely.
Time Frame	28 days
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
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Measured Values

	A - AZD2066	2 - Placebo
Number of Participants Analyzed [units:participants]	30	38
Change in BPI-SF pain interference from baseline to Day 28 [units: Scores on BPI-SF pain interference] Least Squares Mean (Standard Error)	-1.98 (0.376)	-1.72 (0.360)

No statistical analysis provided for Change in BPI-SF pain interference from baseline to Day 28

Serious Adverse Events

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

Reporting Groups

	Description
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Serious Adverse Events

A - AZD2066

2 - Placebo

Total, serious adverse events

# participants affected / at risk

1/42 (2.38%)

0/44 (0.00%)

Psychiatric disorders

Psychotic Disorder¹,^†

# participants affected / at risk

1/42 (2.38%)

0/44 (0.00%)

†	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	5%

Reporting Groups

	Description
A - AZD2066	AZD2066, 12 mg capsule
2 - Placebo	Placebo, capsule

Other Adverse Events

A - AZD2066

2 - Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

30/42 (71.43%)

15/44 (34.09%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

10/42 (23.81%)

3/44 (6.82%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

7/42 (16.67%)

4/44 (9.09%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

4/42 (9.52%)

2/44 (4.55%)

Gastrointestinal disorders

Diarrhea¹,^†

# participants affected / at risk

3/42 (7.14%)

2/44 (4.55%)

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

3/42 (7.14%)

1/44 (2.27%)

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

3/42 (7.14%)

0/44 (0.00%)

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

3/42 (7.14%)

0/44 (0.00%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/42 (0.00%)

3/44 (6.82%)

†	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: No publication or presentation with respect to the study until the earlier of 1) publication of the first Multi-Center Publication and 2) the second anniversary of the completion, or termination of the study. Sponsor to review at least 60 days prior submission. Sponsor can withhold material for submission for additional 90 days

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
Early termination of study for safety reasons leading to fewer subjects analyzed than originally planned.

Results Point of Contact

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

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=229&filename=CSR-D0475C00016.pdf
Download
CSR-D0475C00016.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

Quintiles Worldwide

clinical.studies.ns@quintiles.com

Investigators

Principal Investigator

Biljana Lilja

AstraZeneca R&D Södertälje151 85 Södertälje, Sweden

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=229&filename=CSR-D0475C00016.pdf

CSR-D0475C00016.pdf

Trial Results Summaries