Study to Evaluate the Analgesic Efficacy of 28 Days' Oral Administration of AZD2066 Compared With Placebo in Patients With Painful Diabetic Neuropathy

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00857623
• Collaborator: (none)
• Enrollment: 127
• Locations: 19
• Arms: 2
• Duration (Months): 5.9
• Patients Per Site: 6.7
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate if AZD2066 can relieve the pain arising from painful diabetic neuropathy compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Pain; Diabetic Neuropathy	Drug: AZD2066; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 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 With Placebo in Patients With Painful Diabetic Neuropathy
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: AZD2066; Capsule, once daily, 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28.
Placebo Comparator: 2	Drug: Placebo; Capsule, once daily

Outcome Measures

Primary Outcome Measures

1. Change in Mean Numerical Rating Scale (NRS) Score From Baseline to Last 5 Days of Treatment [From baseline to day 28]

   Change of mean pain intensity from 5-day baseline to the last 5 days of treatment, measured twice daily with NRS (12 hours recall). Mean pain intensity for 5-day baseline period (evening Day -6 to moning 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 numerical rating scale (NRS)(0-10). 0=No pain, 10=Worst pain imaginable.

Secondary Outcome Measures

1. Daily Numerical Rating Scale (NRS) Pain Scores and Change From Baseline Over Time to Day 28. [From baseline to 28 days]

   Mean pain intensity per day (mean of morning and evening NRS values) and change from baseline were calculated for each study day. Baseline value= mean pain intensity for the 5-day baseline period. NRS scale (0- 10) where 0= No pain and 10= Worst pain imaginable.

2. Number of Patients With >=30% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28 [28 days]

   Pain intensity score reduction=(change from baseline at D28/baseline)*100 Responder= pain intensity score reduction ≥30% (yes/no)? Responder rate= (no. of responders/total no. of patients)*100

3. Number of Patients With >=50% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28 [28 days]

   Pain intensity score reduction= (change from baseline D28/baseline)*100 Responder=pain intensity score reduction ≥50% (Yes/No)? Responder rate= (no. of responders/total no. of patients)*100

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

   Patient Global Impression of Change (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

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

   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.

6. Change in McGill Pain Questionnaire Short Form (MPQ-SF) Affective Index From Baseline to Day 28. [From baseline to day 28.]

   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.

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

   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 Numerical rating Scale (NRS) 0-10, where 0=No pain and 10= The worst pain.

8. Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Interference From Baseline to Day 28. [From baseline to 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 Numerical Rating Scale (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.

• Clinical diagnosis of painful diabetic neuropathy.

• non-fertile females

Exclusion Criteria:

• Other pain that may confound assessment of neuropathic pain.

• Ongoing significant peripheral arterial diseases, skin ulcers, or amputation in the lower extremities.

• History of psychotic disorders among first degree relatives.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Reserach Site	Bella Vista	Arkansas	United States
2	Research Site	National City	California	United States
3	Research Site	Walnut Creek	California	United States
4	Research Site	Clearwater	Florida	United States
5	Research Site	Deland	Florida	United States
6	Research Site	Lauderdale Lakes	Florida	United States
7	Research Site	Miami	Florida	United States
8	Research Site	Orlando	Florida	United States
9	Research Site	Pembroke Pines	Florida	United States
10	Research Site	Madisonville	Kentucky	United States
11	Research Site	Owing Mills	Maryland	United States
12	Research Site	Bingham Farms	Michigan	United States
13	Research Site	Willingboro	New Jersey	United States
14	Reasearch Site	Albany	New York	United States
15	Research Site	Winston-Salem	North Carolina	United States
16	Research Site	Indiana	Pennsylvania	United States
17	Research Site	Philadelphia	Pennsylvania	United States
18	Research Site	Houston	Texas	United States
19	Research Site	San Antonio	Texas	United States

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Biljana Lilja, AstraZeneca R&D Södertälje151 85 Södertälje, Sweden
• Principal Investigator: Charles E Argoff, MD, Albany Medical , NY 12208, USA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00857623
• Other Study ID Numbers: D0475C00009
• First Posted: Mar 6, 2009
• Last Update Posted: Nov 12, 2012
• Last Verified: Nov 1, 2012

• Keywords provided by AstraZeneca: Pain; Diabetic Neuropathy; PDN; Analgesia; Efficacy
• Additional relevant MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies

Study Results

Participant Flow

Recruitment Details	This multicenter study was conducted between February 2009 and August 2009in the United States.
Pre-assignment Detail	The study consisted of a 42-day enrollment phase (including washout and baseline period), a 28-day treatment phase (10-day inpatient and 18-day outpatient) where patients were randomized to AZD2066 or placebo, and a 7-day follow-up phase. Patients randomized to treatment with AZD2066 received 12 mg from Days 1 to 4 and 18 mg from Days 5 to 28.

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily. 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28.	Capsule, once daily
Period Title: Overall Study
STARTED	62	65
COMPLETED	48	55
NOT COMPLETED	14	10

Baseline Characteristics

Arm/Group Title	AZD2066	Placebo	Total
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily	Total of all reporting groups
Overall Participants	62	65	127
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (9.2)	57.0 (8.7)	58.1 (8.95)
Sex: Female, Male (Count of Participants)
Female	26 41.9%	31 47.7%	57 44.9%
Male	36 58.1%	34 52.3%	70 55.1%

Outcome Measures

1. Primary Outcome

Title	Change in Mean Numerical Rating Scale (NRS) Score From Baseline to Last 5 Days of Treatment
Description	Change of mean pain intensity from 5-day baseline to the last 5 days of treatment, measured twice daily with NRS (12 hours recall). Mean pain intensity for 5-day baseline period (evening Day -6 to moning 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 numerical rating scale (NRS)(0-10). 0=No pain, 10=Worst pain imaginable.
Time Frame	From baseline to day 28

Outcome Measure Data

Analysis Population Description

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Least Squares Mean (Standard Error) [Scores on a scale]	-2.33 (0.37)	-2.52 (0.36)

2. Secondary Outcome

Title	Daily Numerical Rating Scale (NRS) Pain Scores and Change From Baseline Over Time to Day 28.
Description	Mean pain intensity per day (mean of morning and evening NRS values) and change from baseline were calculated for each study day. Baseline value= mean pain intensity for the 5-day baseline period. NRS scale (0- 10) where 0= No pain and 10= Worst pain imaginable.
Time Frame	From baseline to 28 days

Outcome Measure Data

Analysis Population Description

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Mean (Standard Deviation) [Scores on a scale]	-2.3 (2.2)	-2.5 (2.3)

3. Secondary Outcome

Title	Number of Patients With >=30% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28
Description	Pain intensity score reduction=(change from baseline at D28/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

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Number [Participants]	23 37.1%	25 38.5%

4. Secondary Outcome

Title	Number of Patients With >=50% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28
Description	Pain intensity score reduction= (change from baseline D28/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

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Number [Participants]	15 24.2%	15 23.1%

5. Secondary Outcome

Title	Number of Patients With Patient Global Impression of Change (PGIC) Score of at Least "Much Improved" at Day 28.
Description	Patient Global Impression of Change (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

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Number [Participants]	20 32.3%	28 43.1%

6. Secondary Outcome

Title	Change in McGill Pain Questionnaire Short Form (MPQ-SF) 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	From baseline to day 28.

Outcome Measure Data

Analysis Population Description

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Least Squares Mean (Standard Error) [Scores on a scale]	-6.87 (0.93)	-7.68 (0.88)

7. Secondary Outcome

Title	Change in McGill Pain Questionnaire Short Form (MPQ-SF) 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	From baseline to day 28.

Outcome Measure Data

Analysis Population Description

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Least Squares Mean (Standard Error) [Scores on a scale]	-1.87 (0.35)	-2.06 (0.34)

8. 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 Numerical rating Scale (NRS) 0-10, where 0=No pain and 10= The worst pain.
Time Frame	From baseline to day 28..

Outcome Measure Data

Analysis Population Description

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Least Squares Mean (Standard Error) [Scores on a scale]	-1.99 (0.35)	-2.19 (0.34)

9. Secondary Outcome

Title	Change in Brief Pain Inventory-Short Form (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 Numerical Rating Scale (NRS 0-10), where 0= No interference and 10= Interferes completely.
Time Frame	From baseline to 28 days

Outcome Measure Data

Analysis Population Description

Per Protocol population (PP)

Arm/Group Title	AZD2066	Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Capsule, once daily
Measure Participants	46	51
Least Squares Mean (Standard Error) [Scores on a scale]	-2.13 (0.31)	-2.13 (0.30)

Adverse Events

Arm/Group Title	AZD2066		Placebo
Arm/Group Description	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28		Capsule, once daily
All Cause Mortality
	AZD2066		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZD2066		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)		1/65 (1.5%)
Cardiac disorders
Cardiac failure congestive; Myocardial infarction	0/62 (0%)		1/65 (1.5%)
Injury, poisoning and procedural complications
Hip fracture	1/62 (1.6%)		0/65 (0%)
Other (Not Including Serious) Adverse Events
	AZD2066		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/62 (30.6%)		20/65 (30.8%)
Gastrointestinal disorders
Diarrhea	5/62 (8.1%)		6/65 (9.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/62 (6.5%)		2/65 (3.1%)
Nervous system disorders
Headache	9/62 (14.5%)		11/65 (16.9%)
Dizziness	7/62 (11.3%)		4/65 (6.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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