Study To Evaluate Efficacy, Safety And Tolerability Of Lyrica In Patients With Painful Diabetic Peripheral Neuropathy

Study Overview
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Brief Summary
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Pregabalin has proven effective in previous clinical trails in other countries in relieving neuropathic pain associated with postherpetic neuralgia and painful diabetic neuropathy. This study is being conducted according to China registration requirement to submit a reapplication with new local diabetic peripheral neuropathy study as a commitment plus the existing data to apply for Lyrica pain associated with postherpetic neuralgia indication after Lyrica pain associated with postherpetic neuralgia is approved.

Official Title
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An 11-week Randomized, Double-blind, Multi Center, Placebo-controlled Study To Evaluate The Efficacy, Safety And Tolerability Of Pregabalin (300 Mg/Day) Using A Fixed Dosing Schedule In The Treatment Of Subjects S With Pain Associated With Diabetic Peripheral Neuropathy.

Conditions
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Diabetic Neuropathy, Painful

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo matched with pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged 18 years or older Diagnosis of painful, distal, symmetrical, sensorimotor polyneuropathy which is due to diabetes mellitus (Type 1 or 2), and symptoms of painful diabetic neuropathy for 6 months to 5 years (inclusive). At the baseline and randomization visits, a score of ≥50 mm on the Visual Analogue Scale, at randomization, subjects must have completed at least 5 daily pain interference diaries, and have an average daily pain score of ≥5 over the past 7 days. Patient who are willing and capable to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Women of childbearing potential are willing to use contraception during study. Exclusion Criteria: Subjects with more than 30% decrease on the Pain Visual Analog Scale at randomization as compared to screening; and during the 1 week screening period, with more than one pain score <3 in pain scores. Subject has other kinds of neurological disorder, pain of other reason, or skin condition that could confuse the assessment. Subject with any other serious or unstable condition which in the opinion of the investigator might compromise participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 300 mg/day pregabalin (Lyrica)<br>Patient take pregabalin capsule twice a day | Drug: Pregabalin<br>* Subjects in the pregabalin group will start treatment with pregabalin capsule 150 mg/day for 1 week, then their dose will be increased to 300mg/day. After 1-week titration period, dose must be stable during study, no dose adjustment is permitted, and subject who cannot tolerate 300 mg/day pregabalin will be withdrawn. At the completion of the dose maintenance phase subjects will taper off study medication over a 1-week period. 300 mg/ day subjects will taper to 150 mg/ day.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo matched with pregabalin<br>* Subject will take placebo matched with pregabalin twice a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Mean Pain Score | The daily pain rating scale (DPRS) consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. | Baseline | 
| Change From Baseline in Mean Pain Score at Endpoint | The daily pain rating scale (DPRS) consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The mean endpoint pain score was obtained from the last 7 available DPRS scores of the daily pain diary while the participant was on study medication, up to and including the day after the last Week 8 (Day 57) dose. | Baseline and end of fixed dose phase (Day 63/Week 9)/Early Termination (Study Endpoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | The DPRS consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The weekly mean pain score was the sum of the daily scores divided by the number of diary entries during that week. The overall change is the average change from Weeks 1 to 9. | Baseline and weekly from Weeks 1 to 9 | 
| Baseline Mean Sleep Interference Score | Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered [unable to sleep due to pain]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10. | Baseline | 
| Change From Baseline in Mean Sleep Interference Score at Endpoint | Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered [unable to sleep due to pain]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10. The mean endpoint score was obtained from the last 7 available scores of the daily diary while the participant was on study medication, up to and including the day after the last Week 9 (Day 63) dose. | Baseline and end of fixed dose phase (Day 63/Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered [unable to sleep due to pain]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10. The weekly mean score was the sum of the daily scores divided by the number of diary entries during that week. The overall change is the average change from Weeks 1 to 9. | Baseline and weekly from Weeks 1 to 9 | 
| Percentage of 30 Percent (%) Responders at Endpoint | The DPRS consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. A 30% responder was a participant who had 30% reduction or more in mean pain score at the end of the fixed dose phase (Day 63/Week 9) (Study Endpoint) compared to baseline. | End of fixed dose phase (Day 63/Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | SF-MPQ was assessed according to the participant's answer to the SF-MPQ questionnaire. The score for each composite scale (sensory, affective, and total) was derived by summing the reported intensity value for each item within a particular scale where None=0, Mild=1, Moderate=2, and Severe=3. The sensory score was the sum of the scores of the first 11 pain descriptors (throbbing, shooting, stabbing, sharp, cramping, gnawing, hot-burning, aching, heavy, tender, and splitting) and could range from 0-33. The affective score was the sum of the scores of the last 4 pain descriptors (tiring-exhausting, sickening, fearful, and punishing-cruel) and could range from 0-12. The total score was the sum of the scores of all 15 pain descriptors and could range from 0 to 45. Higher scores indicated greater pain. | Baseline; Weeks 1, 5, and 9 | 
| Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | The VAS was part of the Short Form McGill Pain Questionnaire (SF-MPQ) scale and reflected the overall pain intensity score, The pain VAS was a horizontal line; 100 millimeters (mm) in length, was self-administered by the participant in order to rate pain from 0 (no pain) to 100 (worst possible pain). The PPI was part of the SF-MPQ scale and measured the participant's present pain intensity on a 6-point scale ranging from 0 (no pain) to 5 (excruciating). | Baseline | 
| Change From Baseline in Pain VAS From the SF-MPQ at Endpoint | The VAS was part of the SF-MPQ scale and reflected the overall pain intensity score. The pain VAS was a horizontal line; 100 mm in length, was self-administered by the participant in order to rate pain from 0 (no pain) to 100 (worst possible pain). | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in PPI Scale From the SF-MPQ at Endpoint | The PPI was part of the SF-MPQ scale and measured the participant's present pain intensity on a 6-point scale ranging from 0 (no pain) to 5 (excruciating). | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | The MOS-Sleep Scale was a participant-rated instrument which assesses sleep quantity and quality with 12 items (7 subscale scores: sleep disturbance, snoring, awakening short of breath/with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep; and a 9-item overall sleep problems index). Subscale scores total range: 0-100 (except sleep quantity [range 0-24 hours], optimal sleep [yes:1, no:0]). Higher scores=poorer sleep outcomes (except sleep quantity, adequacy, and optimal sleep). | Baseline | 
| Change From Baseline in MOS-Sleep Scale, Sleep Disturbance Score at Endpoint | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. For sleep disturbance, the subscale score also ranged from 0 to 100, with higher scores representing greater sleep disturbance. | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in MOS-Sleep Scale, Snoring Score at Endpoint | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The snoring subscale score also ranged from 0 to 100, with lower scores indicating less snoring. | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in MOS-Sleep Scale, Awaken Short of Breath Score at Endpoint | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The awaken short of breath subscale also ranged from 0 to 100, with lower scores indicating less difficulty in breathing. | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in MOS-Sleep Scale, Quantity of Sleep Score at Endpoint | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The MOS Sleep Quantity sub-scale scores ranged from 0 to 24 (number of hours slept). | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Percentage of Participants Who Had Optimal Sleep at Endpoint | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The MOS optimal sleep subscale was a binary outcome derived from the sleep quantity responses: the response was YES if sleep quantity was 7 or 8 hours per night. | Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in MOS-Sleep Scale, Sleep Adequacy Score at Endpoint | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The sleep adequacy subscale also ranged from 0 to 100, with higher scores indicating greater sleep adequacy. | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in MOS-Sleep Scale, Somnolence Score at Endpoint | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The somnolence subscale score also ranged from 0 to 100, with lower scores indicating less somnolence. | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in MOS-Sleep Scale, Sleep Problems Index Score at Endpoint | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The sleep problems index subscale score also ranged from 0 to 100, with lower scores indicating fewer sleep problems. | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Clinical Global Impression of Change (CGIC) at Endpoint | The CGIC was a clinician-rated global measure that provided a clinically relevant and easy to interpret account of a clinician's perception of the clinical importance of the participant's improvement or worsening during their involvement in a clinical study. Clinicians rated the participant's overall improvement on a 7-point scale where scores ranged from 1 (very much improved) to 7 (very much worse). | Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Patient Global Impression of Change (PGIC) Score at Endpoint | The PGIC was a participant-rated global measure that provided a clinically relevant and easy to interpret account of a participant's perception of the clinical importance of their own improvement or worsening during their involvement in a clinical study. Participants rated their overall improvement on a 7-point scale where scores ranged from 1 (very much improved) to 7 (very much worse). | Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Baseline Hospital Anxiety and Depression Scale (HADS) Scores | The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe. | Baseline | 
| Change From Baseline in HADS Anxiety Total Score at Endpoint | The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale was comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe. | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 
| Change From Baseline in HADS Depression Total Score at Endpoint | The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale was comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe. | Baseline and Day 63 (Week 9)/Early Termination (Study Endpoint) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Neuropathies, Pain, Efficacy of pregabalin, Placebo controlled