Trial Outcomes & Findings for Study to Evaluate the Analgesic Efficacy of 28 Days' Oral Administration of AZD2066 Compared With Placebo in Patients With Painful Diabetic Neuropathy (NCT NCT00857623)

NCT ID: NCT00857623

Last Updated: 2012-11-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 127 participants
• Primary outcome timeframe: From baseline to day 28
• Results posted on: 2012-11-12

Participant Flow

This multicenter study was conducted between February 2009 and August 2009in the United States.

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.

Participant milestones

Measure	AZD2066 Capsule, once daily. 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28.	Placebo Capsule, once daily
Overall Study STARTED	62	65
Overall Study COMPLETED	48	55
Overall Study NOT COMPLETED	14	10

Reasons for withdrawal

Measure	AZD2066 Capsule, once daily. 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28.	Placebo Capsule, once daily
Overall Study Adverse Event	5	2
Overall Study Study-specific discontinuation criteria	5	3
Overall Study Withdrawal by Subject	2	1
Overall Study Lack of Efficacy	1	1
Overall Study Severe non-compliance to protocol	1	1
Overall Study Intake of prohibited medication	0	1
Overall Study Positive for HEP C	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AZD2066 n=62 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=65 Participants Capsule, once daily	Total n=127 Participants Total of all reporting groups
Age Continuous	59.2 years STANDARD_DEVIATION 9.2 • n=5 Participants	57.0 years STANDARD_DEVIATION 8.7 • n=7 Participants	58.1 years STANDARD_DEVIATION 8.95 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	31 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	34 Participants n=7 Participants	70 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to day 28

Population: Per Protocol population (PP)

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.

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Change in Mean Numerical Rating Scale (NRS) Score From Baseline to Last 5 Days of Treatment	-2.33 Scores on a scale Standard Error 0.37	-2.52 Scores on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: From baseline to 28 days

Population: Per Protocol population (PP)

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.

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Daily Numerical Rating Scale (NRS) Pain Scores and Change From Baseline Over Time to Day 28.	-2.3 Scores on a scale Standard Deviation 2.2	-2.5 Scores on a scale Standard Deviation 2.3

SECONDARY outcome

Timeframe: 28 days

Population: Per Protocol population (PP)

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

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Number of Patients With >=30% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28	23 Participants	25 Participants

SECONDARY outcome

Timeframe: 28 days

Population: Per Protocol population (PP)

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

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Number of Patients With >=50% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28	15 Participants	15 Participants

SECONDARY outcome

Timeframe: 28 days

Population: Per Protocol population (PP)

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

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Number of Patients With Patient Global Impression of Change (PGIC) Score of at Least "Much Improved" at Day 28.	20 Participants	28 Participants

SECONDARY outcome

Timeframe: From baseline to day 28.

Population: Per Protocol population (PP)

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.

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Change in McGill Pain Questionnaire Short Form (MPQ-SF) Sensory Index From Baseline to Day 28.	-6.87 Scores on a scale Standard Error 0.93	-7.68 Scores on a scale Standard Error 0.88

SECONDARY outcome

Timeframe: From baseline to day 28.

Population: Per Protocol population (PP)

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.

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Change in McGill Pain Questionnaire Short Form (MPQ-SF) Affective Index From Baseline to Day 28.	-1.87 Scores on a scale Standard Error 0.35	-2.06 Scores on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: From baseline to day 28..

Population: Per Protocol population (PP)

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.

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Severity From Baseline to Day 28.	-1.99 Scores on a scale Standard Error 0.35	-2.19 Scores on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: From baseline to 28 days

Population: Per Protocol population (PP)

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.

Outcome measures

Measure	AZD2066 n=46 Participants Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=51 Participants Capsule, once daily
Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Interference From Baseline to Day 28.	-2.13 Scores on a scale Standard Error 0.31	-2.13 Scores on a scale Standard Error 0.30

Adverse Events

AZD2066

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD2066 n=62 participants at risk Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=65 participants at risk Capsule, once daily
Injury, poisoning and procedural complications Hip fracture	1.6% 1/62	0.00% 0/65
Cardiac disorders Cardiac failure congestive; Myocardial infarction	0.00% 0/62	1.5% 1/65

Other adverse events

Measure	AZD2066 n=62 participants at risk Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	Placebo n=65 participants at risk Capsule, once daily
Nervous system disorders Headache	14.5% 9/62	16.9% 11/65
Nervous system disorders Dizziness	11.3% 7/62	6.2% 4/65
Gastrointestinal disorders Diarrhea	8.1% 5/62	9.2% 6/65
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 4/62	3.1% 2/65

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER