A Study To Compare Pregabalin/PF-00489791 Combination Versus Pregabalin Alone In Post-Herpetic Neuralgia

Study Overview
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Brief Summary
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Pregabalin is an alpha-2 delta ligand approved for the treatment of neuropathic pain, however, not all patients will respond to this drug. This study will compare the efficacy of pregabalin when administered with an experimental drug PF-00489791, in patients with post-herpetic neuralgia. The efficacy of this combination will be compared to pregabalin alone.

Official Title
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A TWO WEEK DOUBLE-BLIND PLACEBO-CONTROLLED CROSSOVER STUDY TO COMPARE THE EFFICACY AND SAFETY OF A PREGABALIN/PF-00489791 COMBINATION VERSUS PREGABALIN ALONE IN PATIENTS WITH POST-HERPETIC NEURALGIA

Conditions
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Postherpetic Neuralgia

Intervention / Treatment
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* Drug: pregabalin
* Drug: pregabalin/PF-00489791
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of non-childbearing potential Pain present for more than 3 months after healing of herpes zoster skin rash VAS score of >=40mm at screening and baseline visits Exclusion Criteria: Patients with pain conditions which might impair the assessment of postherpetic neuralgia Skin conditions in the affected dermatome that could alter sensation other than postherpetic neuralgia History or diagnosis of DSM IV major depressive disorder

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: pregabalin<br>* 75mg bid titrating to 150mg bid on day 4<br>|
| Experimental: 2<br> | Drug: pregabalin/PF-00489791<br>* Pregabalin 75mg bid titrating to 150mg bid on day 4; PF-00489791: 4mg od titrating to 10mg od on day 4<br>|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Score on Daily Pain Rating Scale (DPRS) | Pain was assessed by using a daily pain rating scale that consisted of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain), higher scores indicate more pain intensity. Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. Self-assessment was performed daily. The mean pain score was defined as the mean of the last 7 daily pain ratings scale scores while taking study medication, at end of each treatment period: Period 1 (Week 2) and Period 2 (Week 6), respectively. Mean pain score had a score range of 0 (no pain) to 10 (worst possible pain), higher scores indicate more pain. Cumulative data of mean pain scores at end of treatment for both the periods was calculated and reported in terms of adjusted mean and standard error. | End of treatment period (included both Week 2 and Week 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Patient Global Impression of Change (PGIC) Score | The PGIC is a participant-rated instrument that measures change in the participants' overall status on a 7-point scale. Scores range from 1 (very much improved) to 7 (very much worse), lower scores indicated more improvement. PGIC was evaluated using 3 categories: improvement (scores 1-3), no change (score 4), and worsening (scores 5-7). In this outcome measure percentage of participants with categories: improved, no change and worsening, based on PGIC score were reported. Cumulative data at end of treatment for both the periods (Period 1 [Week 2] and Period 2 [Week6]) was calculated and reported. | End of treatment period (included both Week 2 and Week 6) | 
| Pain Visual Analogue Scale (VAS) at Baseline and Week 4 | Participants marked intensity of the pain on a scale, ranging from 0 millimeters (mm) = no pain to 100 mm = worst possible pain, where higher scores indicate more pain. | Baseline, Week 4 | 
| Neuropathic Pain Symptom Inventory (NPSI) | Participant rated 10-item questionnaire to evaluate different symptoms of neuropathic pain (spontaneous pain like [item 1 to 3]: burning, squeezing, pressure; painful attack like [item 4 to 5]: electric shock, stabbing; pain provoked on [item 6 to 8]: light touching, pressure, contact with something cold; abnormal sensations like [item 9 to 10]: pins and needles, tingling). Each item was rated on an 11-point numerical scale range: 0 (absence of pain) to 10 (maximum intensity of pain). Total NPSI scale ranged from 0 (no pain) to 100 (maximum pain). Higher scores indicate a greater intensity of pain. Cumulative data of NPSI scale at end of treatment for both the periods (Period 1 [Week 2] and Period 2 [Week 6]) was calculated and reported in terms of adjusted mean and standard error. | End of treatment period (included both Week 2 and Week 6) | 
| Number of Participants With Clinically Significant Vital Signs Abnormalities | Vital signs abnormalities included sitting, standing: systolic, diastolic blood pressure and heart rate. Clinical significance was judged by investigator. | Baseline up to Week 7 | 
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Criteria for ECG abnormalities: Maximum QTc (corrected QT) interval, QTcB (Bazett's correction formula) and QTcF (Fridericia's correction formula): 450 to less than (<) 480 milliseconds (msec), 480 to <500 msec and greater than equal to (>=) 500 msec; Maximum QTc interval increase from baseline: >=30 to <60 and >=60 (msec); PR interval: >=300 msec and percent change >=25 or 50 percent; QRS complex: percent change >=25 or 50 percent. Clinical significance was judged by investigator. | Baseline up to Week 7 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Hematology | Criteria for hematology abnormalities included Hemoglobin: <0.8*lower limit of normal (LLN) and hematocrit: <0.8*LLN. Clinical significance was judged by investigator. | Baseline up to Week 7 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Clinical Chemistry | Criteria for clinical chemistry abnormalities included total bilirubin: greater than (>) 1.5*upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase: >3.0*ULN; total protein, albumin: <0.8*LLN or >1.2*ULN; blood urea nitrogen, creatinine: >1.3*ULN; uric acid: >1.2*ULN; sodium: <0.95*LLN or >1.05*ULN; potassium, chloride, calcium: <0.9*LLN or >1.1*ULN; creatine kinase: >2.0*ULN. Clinical significance was judged by investigator. | Baseline up to Week 7 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities: Urinalysis | Urinalysis abnormalities criteria included: urine specific gravity: <1.003 to >1.030; urine pH: <4.5 to >8; urine glucose, urine ketones, urine proteins, urine blood/hemoglobin: >=1. Clinical significance was judged by investigator. | Baseline up to Week 7 |