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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00857623

Enrollment

127

Registered

2009-03-06

Start date

2009-02-28

Completion date

2009-08-31

Last updated

2012-11-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pain, Diabetic Neuropathy

Keywords

Pain, Diabetic Neuropathy, PDN, Analgesia, Efficacy

Brief summary

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

Interventions

DRUGAZD2066

Capsule, once daily, 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28.

DRUGPlacebo

Capsule, once daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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
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
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.
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.
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.
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.
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.

Countries

United States

Participant flow

Recruitment details

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

Pre-assignment details

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.

Participants by arm

Arm	Count
AZD2066 Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28	62
Placebo Capsule, once daily	65
Total	127

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	5	2
Overall Study	Intake of prohibited medication	0	1
Overall Study	Lack of Efficacy	1	1
Overall Study	Positive for HEP C	0	1
Overall Study	Severe non-compliance to protocol	1	1
Overall Study	Study-specific discontinuation criteria	5	3
Overall Study	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	AZD2066	Placebo	Total
Age Continuous	59.2 years STANDARD_DEVIATION 9.2	57.0 years STANDARD_DEVIATION 8.7	58.1 years STANDARD_DEVIATION 8.95
Sex: Female, Male Female	26 Participants	31 Participants	57 Participants
Sex: Female, Male Male	36 Participants	34 Participants	70 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	19 / 62	20 / 65
serious Total, serious adverse events	1 / 62	1 / 65

Outcome results

Primary

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

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