Study Of Pregabalin (Lyrica) In Patients With Painful Diabetic Peripheral Neuropathy

Study Overview
=================
Brief Summary
-----------------
Patients will be switched from their current medication for painful diabetic peripheral neuropathy to evaluate the safety and efficacy of pregabalin as compared to placebo. All patients will receive pregabalin, and half of patients will receive placebo at some point during the study.

Official Title
-----------------
A PHASE 3B MULTICENTER, DOUBLE-BLIND, RANDOMIZED WITHDRAWAL EFFICACY AND SAFETY STUDY OF PREGABALIN IN THE TREATMENT OF PATIENTS WITH INADEQUATELY TREATED PAINFUL DIABETIC PERIPHERAL NEUROPATHY

Conditions
-----------------
Diabetic Neuropathy, Painful

Intervention / Treatment
-----------------
* Drug: pregabalin (Lyrica)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have painful diabetic peripheral neuropathy and be receiving treatment for this condition. Exclusion Criteria: Patients with other pain conditions cannot participate.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pregabalin (Lyrica)<br> | Drug: pregabalin (Lyrica)<br>* Lyrica 150-300 mg/day. Medication is supplied as capsules and given 3 times daily.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo is supplied as capsules and given 3 times daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Single-Blind Baseline in Mean Pain Score at Week 19 During Double-Blind Phase | Mean pain score was defined as the mean of the last 7 daily diary pain ratings. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. SB baseline refers to the last 7 pain diary entries up to and including Day 1. | SB Baseline, Week 19 (DB Phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Loss of Pain Response (Double-Blind Phase) | Time to loss of pain response (based on the daily pain diary data) during the DB treatment phase was analyzed using survival analysis technique. Loss of pain response was defined as less than (<) 15% pain response relative to the SB baseline. SB baseline refers to the last 7 pain diary entries up to and including Day 1. | SB Baseline up to Week 19 | 
| Change From Single-Blind Baseline in Mean Pain Score at Week 6 During Single-Blind Phase | Mean pain score was defined as the mean of the last 7 daily diary pain ratings. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. SB baseline refers to the last 7 pain diary entries up to and including Day 1. | SB Baseline, Week 6 (SB Phase) | 
| Weekly Mean Pain Scores (Single-Blind Phase) | Weekly mean pain score was defined as the mean of the daily diary pain ratings split into 7 day intervals. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. | Week 1, 2, 3, 4, 5, 6 | 
| Weekly Mean Pain Scores (Double-Blind Phase) | Weekly mean pain score was defined as the mean of the daily diary pain ratings split into 7 day intervals. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. SB baseline refers to the last 7 pain diary entries up to and including Day 1. DB baseline refers to the last 7 pain diary entries up to and including DB Day 1. | DB Baseline, Week 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 | 
| Percentage of Participants With At Least 30 Percent and 50 Percent Reduction in Mean Pain Score (Single-Blind Phase) | Mean pain score was defined as the mean of the last 7 daily diary pain ratings. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. Percentage of participants who had at least 30% and 50% pain reduction from SB baseline to Week 6 is reported. SB baseline refers to the last 7 pain diary entries up to and including Day 1. | Week 6 | 
| Percentage of Participants With At Least 30 Percent and 50 Percent Reduction in Mean Pain Score (Double-Blind Phase) | Mean pain score was defined as the mean of the last 7 daily diary pain ratings. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. Percentage of participants who had at least 30% and 50% pain reduction from SB baseline to Week 19 is reported. | Week 19 | 
| Patient Global Impression of Change (PGIC) (Single-Blind Phase) | PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). Number of participants in each category are reported. | Week 6 | 
| Patient Global Impression of Change (PGIC) (Double-Blind Phase) | PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). Number of participants in each category are reported. | Week 19 | 
| Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) | Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales: sleep disturbance (range 0-100), snoring (range 0-100), awaken short of breath (SOB) or with headache (range 0-100), sleep adequacy (range 0-100), somnolence (range: 0-100); sleep quantity (range: 0-24), optimal sleep (yes/no), and 9 item index measures of sleep disturbance provide composite scores: sleep problems index (range 0-100). Except adequacy, optimal sleep and quantity, higher scores=more impairment. | SB Baseline, Week 6 | 
| Medical Outcomes Study -Sleep Scale (MOS-SS) (Double-Blind Phase) | Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales: sleep disturbance (range 0-100), snoring (range 0-100), awaken short of breath (SOB) or with headache (range 0-100), sleep adequacy (range 0-100), somnolence (range: 0-100); sleep quantity (range: 0-24), optimal sleep (yes/no), and 9 item index measures of sleep disturbance provide composite scores: sleep problems index (range 0-100). Except adequacy, optimal sleep and quantity, higher scores=more impairment. | Week 19 | 
| Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) (Single-Blind Phase) | MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, and 9 item index measures of sleep disturbance provide composite scores: sleep problems index. Participants responded whether their sleep was optimal or not optimal by choosing yes or no. | SB Baseline, Week 6 | 
| Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) (Double-Blind Phase) | MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, and 9 item index measures of sleep disturbance provide composite scores: sleep problems index. Participants responded whether their sleep was optimal or not optimal by choosing yes or no. | Week 19 | 
| Weekly Mean Sleep Interference Score (Single-Blind Phase) | Weekly mean sleep interference score was defined as the mean of the daily sleep interference diary ratings split into 7 day intervals. Participants rated how painful DPN has interfered with their sleep during the past 24 hours on an 11-point numeric rating scale ranging from 0 = does not interfere with sleep to 10 = completely interferes (unable to sleep due to pain). SB baseline refers to the last 7 pain diary entries up to and including Day 1. | SB Baseline, Week 1, 2, 3, 4, 5, 6 | 
| Weekly Mean Sleep Interference Score (Double-Blind Phase) | Weekly mean sleep interference score was defined as the mean of the daily sleep interference diary ratings split into 7 day intervals. Participants rated how painful DPN has interfered with their sleep during the past 24 hours on an 11-point numeric rating scale ranging from 0 = does not interfere with sleep to 10 = completely interferes (unable to sleep due to pain). | DB Baseline, Week 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 | 
| Endpoint Mean Sleep Interference Score (Single-Blind Phase) | Endpoint mean sleep interference score was defined as the mean of the last 7 sleep interference diaries while receiving SB treatment. Participants rated how painful DPN has interfered with their sleep during the past 24 hours on an 11-point numeric rating scale ranging from 0 = does not interfere to 10 = completely interferes (unable to sleep due to pain). | Week 6 | 
| Endpoint Mean Sleep Interference Score (Double-Blind Phase) | Endpoint mean sleep interference score was defined as the mean of the last 7 sleep interference diaries while receiving DB treatment. Participants rated how painful DPN has interfered with their sleep during the past 24 hours on an 11-point numeric rating scale ranging from 0 = does not interfere to 10 = completely interferes (unable to sleep due to pain). | Week 19 | 
| Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) | QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. Consists of 5 domains: Physical functioning(Ph Fn)/large fiber (sum of item 8, 11, 13-15, 24, 27-35; range -4 to 56); Activities of daily living (sum of item 12, 22, 23, 25, 26; range 0 to 20); Symptoms (sum of item 1-7, 9; range 0 to 32); Small fiber (sum of item 10, 16, 17, 18; range 0 to 16); Autonomic (sum of item 19, 20, 21; range 0 to 12) and total QOL score (sum of items 1-35) range: -4 to 136. Higher score implied worse QOL. | SB Baseline, Week 6 | 
| Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Double-Blind Phase) | QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. Consists of 5 domains: Physical functioning(Ph Fn)/large fiber (sum of item 8, 11, 13-15, 24, 27-35; range -4 to 56); Activities of daily living (sum of item 12, 22, 23, 25, 26; range 0 to 20); Symptoms (sum of item 1-7, 9; range 0 to 32); Small fiber (sum of item 10, 16, 17, 18; range 0 to 16); Autonomic (sum of item 19, 20, 21; range 0 to 12) and total QOL score (sum of items 1-35) range: -4 to 136. Higher score implied worse QOL. | Week 19 | 
| Pain Visual Analog Scale (VAS) (Single-Blind Phase) | Participants rated their pain on a 100 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm = no pain to 100 mm = worst possible pain. | SB Baseline, Week 6 | 
| Pain Visual Analog Scale (VAS) (Double-Blind Phase) | Participants rated their pain on a 100 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm = no pain to 100 mm = worst possible pain. | Week 19 | 
| Brief Pain Inventory-Short Form (BPI-sf) (Single-Blind Phase) | BPI-sf: self-administered questionnaire developed to assess severity, impact of pain on daily functions, consisted of 5 questions. Questions 1-4 measured the severity of pain based on pain experienced over the past 24-hours on an 11-point scale ranged from 0 (no pain) to10 (worst possible pain). Question 5: 7 item subsets that measured level of interference of pain on daily functions on an 11-point scale ranged from 0 (does not interfere) to 10 (completely interferes). | SB Baseline, Week 6 | 
| Brief Pain Inventory-Short Form (BPI-sf) (Double-Blind Phase) | BPI-sf: self-administered questionnaire developed to assess severity, impact of pain on daily functions, consisted of 5 questions. Questions 1-4 measured the severity of pain based on pain experienced over the past 24-hours on an 11-point scale ranged from 0 (no pain) to10 (worst possible pain). Question 5: 7 item subsets that measured level of interference of pain on daily functions on an 11-point scale ranged from 0 (does not interfere) to 10 (completely interferes). | Week 19 | 
| Hospital Anxiety and Depression Scale (HADS) (Single-Blind Phase) | HADS: self-administered questionnaire, consists of 2 sub-scales; measuring anxiety (HADS-A), and depression (HADS-D). Each sub-scale consists of 7 items on which participants responded as to how each item applies to them on a 4-point scale ranging from 0 (no anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range for each sub-scale = 0 to 21, where higher score indicates more severe anxiety or depression. | SB Baseline, Week 6 | 
| Hospital Anxiety and Depression Scale (HADS) (Double-Blind Phase) | HADS: self-administered questionnaire, consists of 2 sub-scales; measuring anxiety (HADS-A), and depression (HADS-D). Each sub-scale consists of 7 items on which participants responded as to how each item applies to them on a 4-point scale ranging from 0 (no anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range for each sub-scale = 0 to 21, where higher score indicates more severe anxiety or depression. | Week 19 | 
| Patient Global Evaluation of Study Medication (GESM) (Single-Blind Phase) | GESM: single-item, self-administered treatment satisfaction questionnaire. Participants answered how would you rate the study medication you received for pain? on a 7-point scale ranging from 1 (very satisfied) to 7 (very dissatisfied). Number of participants in each category are reported. | Week 6 | 
| Patient Global Evaluation of Study Medication (GESM) (Double-Blind Phase) | GESM: single-item, self-administered treatment satisfaction questionnaire. Participants answered how would you rate the study medication you received for pain? on a 7-point scale ranging from 1 (very satisfied) to 7 (very dissatisfied). Number of participants in each category are reported. | Week 19 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetic peripheral neuropathy, Lyrica, pregabalin, pain