NP-MH: AZD2066 Neuropathic Pain - Mechanical Hypersensitivity

• Sponsor: AstraZeneca (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00939094
• Collaborator: Quintiles, Inc. (Industry)
• Enrollment: 87
• Locations: 38
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate if 28 days of treatment with AZD2066 compared to placebo can relieve the pain arising from the nervous system when the patients are touched by something that should not cause pain or have severe pain when they are touched by something that should only cause a little pain.

Condition or Disease	Intervention/Treatment	Phase
Neuropathic Pain; Mechanical Hypersensitivity	Drug: AZD2066; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: AZD2066; Capsule, once daily
Placebo Comparator: B	Drug: Placebo; Capsule, once daily

Outcome Measures

Primary Outcome Measures

1. Change in Mean Numerical Rating Scale (NRS) Pain Score From Baseline to Last 5 Days on Treatment [Change in mean pain intensity from 5-day baseline to the last 5 days on treatment, measure twice daily with NRS (12-hour recall)]

   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.

Secondary Outcome Measures

1. Patients With ≥30% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28 [28 days]

   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

2. Patients With ≥50% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28 [28 days]

   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

3. Patients With Patient Global Impression of Change (PGIC) Score of at Least "Much Improved" (Responder Rate) at Day 28 [28 days]

   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

4. Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index From Baseline to Day 28 [28 days]

   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.

5. Change in SF-MPQ Affective Index From Baseline to Day 28 [28 days]

   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.

6. Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Severity From Baseline to Day 28 [28 days]

   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.

7. Change in BPI-SF Pain Interference From Baseline to Day 28 [28 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures.

• Male or non-fertile females

• Painful symptoms due to neuropathic pain for a period of 3 months to 5 years, associated with mechanical allodynia and/or punctate hyperalgesia.

Exclusion Criteria:

• Other pain that may confound assessment of neuropathic pain.

• Diagnosis of any severe neurological disease.

• History of significant psychiatric disease/condition and/or history of psychotic disorders among first degree relatives.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Tucson	Arizona	United States
2	Research Site	Los Angeles	California	United States
3	Research Site	Sacramento	California	United States
4	Research Site	San Francisco	California	United States
5	Research Site	Walnut Creek	California	United States
6	Research Site	Boulder	Colorado	United States
7	Research Site	Atlantis	Florida	United States
8	Research Site	Aventura	Florida	United States
9	Research Site	Clearwater	Florida	United States
10	Research Site	Fort Myers	Florida	United States
11	Research Site	Orlando	Florida	United States
12	Research Site	Palm Beach Gardens	Florida	United States
13	Research Site	Sarasota	Florida	United States
14	Research Site	St Petersburg	Florida	United States
15	Research Site	Sunrise	Florida	United States
16	Research Site	Canton	Georgia	United States
17	Research Site	Marietta	Georgia	United States
18	Research Site	Evansville	Indiana	United States
19	Research Site	New Orleans	Louisiana	United States
20	Research Site	Brockton	Massachusetts	United States
21	Research Site	Bingham Farms	Michigan	United States
22	Research Site	Las Vegas	Nevada	United States
23	Research Site	Reno	Nevada	United States
24	Research Site	Lumberton	New Jersey	United States
25	Research Site	Willingboro	New Jersey	United States
26	Research Site	Albuquerque	New Mexico	United States
27	Research Site	Jacksonville	North Carolina	United States
28	Research Site	Winston-salem	North Carolina	United States
29	Research Site	Kettering	Ohio	United States
30	Research Site	Portland	Oregon	United States
31	Research Site	Bridgeville	Pennsylvania	United States
32	Research Site	Philadelphia	Pennsylvania	United States
33	Research Site	Austin	Texas	United States
34	Research Site	Dallas	Texas	United States
35	Research Site	Irving	Texas	United States
36	Research Site	Lexington	Texas	United States
37	Research Site	Longview	Texas	United States
38	Research Site	San Antonio	Texas	United States

Sponsors and Collaborators

• AstraZeneca
• Quintiles, Inc.

Investigators

• Study Director: Biljana Lilja, AstraZeneca R&D Södertälje151 85 Södertälje, Sweden
• Principal Investigator: Brett Stacey, Oregon Health and Science University Comprehensive Pain Clinic, Portland, OR 97239, USA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00939094
• Other Study ID Numbers: D0475C00016
• First Posted: Jul 14, 2009
• Last Update Posted: Sep 27, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by AstraZeneca: Pain, Mechanical Hypersensitivity; Allodynia; Efficacy; analgesia; Neuropathic
• Additional relevant MeSH terms: Neuralgia; Hypersensitivity

Study Results

Participant Flow

Recruitment Details	This multicenter study was conducted between August 2009 and November 2010 in the United States.
Pre-assignment Detail	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.

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Period Title: Overall Study
STARTED	42	45
COMPLETED	28	35
NOT COMPLETED	14	10

Baseline Characteristics

Arm/Group Title	A - AZD2066	2 - Placebo	Total
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule	Total of all reporting groups
Overall Participants	42	45	87
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.1 (9.25)	59.3 (14.31)	58.7 (12.8)
Sex: Female, Male (Count of Participants)
Female	24 57.1%	18 40%	42 48.3%
Male	18 42.9%	27 60%	45 51.7%

Outcome Measures

1. Primary Outcome

Title	Change in Mean Numerical Rating Scale (NRS) Pain Score From Baseline to Last 5 Days on Treatment
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Measure Participants	30	38
Least Squares Mean (Standard Error) [Scores (units) on NRS]	-2.14 (0.358)	-1.26 (0.337)

2. Secondary Outcome

Title	Patients With ≥30% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Measure Participants	30	38
Number [Participants]	16 38.1%	10 22.2%

3. Secondary Outcome

Title	Patients With ≥50% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Measure Participants	30	38
Number [Participants]	10 23.8%	5 11.1%

4. Secondary Outcome

Title	Patients With Patient Global Impression of Change (PGIC) Score of at Least "Much Improved" (Responder Rate) at Day 28
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Measure Participants	30	38
Number [Patients]	10	10

5. Secondary Outcome

Title	Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index From Baseline to Day 28
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Measure Participants	30	38
Least Squares Mean (Standard Error) [Scores (units) on SF-MPQ Sensory Index]	-6.39 (1.278)	-3.98 (1.188)

6. Secondary Outcome

Title	Change in SF-MPQ Affective Index From Baseline to Day 28
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Measure Participants	30	38
Least Squares Mean (Standard Deviation) [Scores (units) on SF-MPQ Affective Index]	-1.1 (0.52)	-0.9 (0.50)

7. Secondary Outcome

Title	Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Severity From Baseline to Day 28
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Measure Participants	30	38
Least Squares Mean (Standard Error) [Scores (units) on BPI-SF pain severity]	-2.12 (0.385)	-1.25 (0.360)

8. Secondary Outcome

Title	Change in BPI-SF Pain Interference From Baseline to Day 28
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - AZD2066	2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule	Placebo, capsule
Measure Participants	30	38
Least Squares Mean (Standard Error) [Scores on BPI-SF pain interference]	-1.98 (0.376)	-1.72 (0.360)

Adverse Events

Arm/Group Title	A - AZD2066		2 - Placebo
Arm/Group Description	AZD2066, 12 mg capsule		Placebo, capsule
All Cause Mortality
	A - AZD2066		2 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	A - AZD2066		2 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/42 (2.4%)		0/44 (0%)
Psychiatric disorders
Psychotic Disorder	1/42 (2.4%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	A - AZD2066		2 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/42 (71.4%)		15/44 (34.1%)
Gastrointestinal disorders
Diarrhea	3/42 (7.1%)		2/44 (4.5%)
Constipation	0/42 (0%)		3/44 (6.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/42 (9.5%)		2/44 (4.5%)
Nervous system disorders
Dizziness	10/42 (23.8%)		3/44 (6.8%)
Headache	7/42 (16.7%)		4/44 (9.1%)
Paraesthesia	3/42 (7.1%)		0/44 (0%)
Somnolence	3/42 (7.1%)		0/44 (0%)
Psychiatric disorders
Insomnia	3/42 (7.1%)		1/44 (2.3%)

Limitations/Caveats

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

More Information

Certain Agreements

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

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