A Clinical Trial To Evaluate PF-05089771 On Its Own And As An Add-On Therapy To Pregabalin (Lyrica) For The Treatment Of Pain Due To Diabetic Peripheral Neuropathy (DPN)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of PF-05089771 as a monotherapy and as an add-on to pregabalin for the treatment of painful diabetic peripheral neuropathy (DPN)

Official Title
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A Randomized Double Blind Placebo And Active Controlled Parallel Group Phase 2 Study To Evaluate PF-05089771 As A Monotherapy And As An Add-on To Pregabalin For The Treatment Of Painful Diabetic Peripheral Neuropathy

Conditions
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Diabetic Neuropathy, Painful

Intervention / Treatment
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* Drug: PF-05089771 150 mg
* Drug: Matched placebo for PF-05089771 150 mg and pregabalin 300 mg
* Drug: Pregabalin 300 mg
* Drug: PF-05089771 150 mg + Pregabalin 300 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 years to 80 years. Diagnosis of Type 2 diabetes mellitlus (T2DM) with current glycosylated hemoglobin A1c (HbA1c) levels of ≤ 11% at Screening and on a stable antidiabetic medication regimen for at least 30 days prior to randomization. Presence of ongoing pain due to DPN for at least 6 months. Willing to discontinue protocol-specified prohibited pain medications for DPN throughout the duration of the study. Exclusion Criteria: Painful neuropathies or painful conditions other than DPN that may confound evaluation of pain due to DPN during the study. Subjects who have failed previously on pregabalin (at the recommended label dose and for adequate duration) due to lack of efficacy. Subjects with any clinically significant medical or psychiatric conditions or clinically significant laboratory test abnormalities. Pregnant women, lactating mothers, men with partners currently pregnant, women suspected of being pregnant, and women who wish to be pregnant during the course of the clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: PF-05089771<br> | Drug: PF-05089771 150 mg<br>* PF-05089771 150 mg twice daily oral dosing with capsules. Treatment period = 4 weeks.<br>|
| Experimental: Placebo<br> | Drug: Matched placebo for PF-05089771 150 mg and pregabalin 300 mg<br>* Matched placebo for PF-05089771 150 mg twice daily and pregabalin 150 mg twice daily oral dosing with capsules. Treatment period = 4 weeks.<br>|
| Experimental: Pregabalin<br> | Drug: Pregabalin 300 mg<br>* Pregabalin 150 mg twice daily oral dosing with capsules. Treatment period = 4 weeks.<br>|
| Experimental: PF-05089771 + Pregabalin<br> | Drug: PF-05089771 150 mg + Pregabalin 300 mg<br>* PF-05089771 150 mg twice daily oral capsules with pregabalin 150 mg twice daily oral capsules. Treatment period = 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Pain Numeric Rating Scale (NRS) | The endpoint average pain score, based on the mean of the last 7 days' daily pain numeric rating scale (NRS) scores at (NRS is an 11-point scale where 0 = no pain and 10 = worst possible pain) from the daily pain diaries while receiving study medication during the treatment period. | Baseline, Week 1, Week 2, Week 3 and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate Based on a 30% Improvement in Mean Pain Response Using the Daily Pain NRS Score | Percentage of participants that received ≥30% improvement from baseline in mean pain response (from the daily pain diary). | Baseline, Week 1, Week 2, Week 3 and Week 4 | 
| Responder Rate Based on a 50% Improvement in Mean Pain Response Using the Daily Pain NRS Score | Percentage of participants that received ≥50% improvement from baseline in mean pain response (from the daily pain diary). | Baseline, Week 1, Week 2, Week 3, and Week 4 | 
| Neuropathic Pain Symptom Inventory (NPSI) - Burning (Superficial) Spontaneous Pain | Participants rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning [superficial] spontaneous pain, pressing [deep] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia [P/D]) including 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. A score in each dimension and also a total score (from 0-100) is generated using data from the questionnaire. Higher score indicates a greater intensity of pain. | Baseline, Week 2, and Week 4 | 
| Neuropathic Pain Symptom Inventory (NPSI) - Pressing (Deep) Spontaneous Pain | Participant rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning [superficial] spontaneous pain, pressing [deep] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia [P/D]) including 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. A score in each dimension and also a total score (from 0-100) is generated using data from the questionnaire. Higher score indicates a greater intensity of pain. | Baseline, Week 2 and Week 4 | 
| Neuropathic Pain Symptom Inventory (NPSI) - Paroxysmal Pain | Participant rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning [superficial] spontaneous pain, pressing [deep] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia [P/D]) including 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. A score in each dimension and also a total score (from 0-100) is generated using data from the questionnaire. Higher score indicates a greater intensity of pain. | Baseline, Week 2, and Week 4 | 
| Neuropathic Pain Symptom Inventory (NPSI) - Evoked Pain | Participant rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning [superficial] spontaneous pain, pressing [deep] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia [P/D]) including 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. A score in each dimension and also a total score (from 0-100) is generated using data from the questionnaire. Higher score indicates a greater intensity of pain. | Baseline, Week 2 and Week 4 | 
| Neuropathic Pain Symptom Inventory (NPSI) - Paresthesia/Dysethesia | Participant rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning [superficial] spontaneous pain, pressing [deep] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia [P/D]) including 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. A score in each dimension and also a total score (from 0-100) is generated using data from the questionnaire. Higher score indicates a greater intensity of pain. | Baseline, Week 2 and Week 4 | 
| Neuropathic Pain Symptom Inventory (NPSI) - Total Score | Participant rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning [superficial] spontaneous pain, pressing [deep] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia [P/D]) including 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. A score in each dimension and also a total score (from 0-100) is generated using data from the questionnaire. Higher score indicates a greater intensity of pain. | Baseline, Week 2 and Week 4 | 
| Patient's Global Impression of Change Score (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) at week 4. The PGIC was combined to produce a 3-point scale, Improved, No Change and Worse. | Baseline, Week 2, and Week 4 | 
| Daily Sleep Interference Scale Score (DSIS). | Participant rated 11-point Likert scale ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep) during past 24-hour period. Higher score indicates a greater level of sleep disturbance. Self-assessment performed daily on awakening prior to taking study medication. This score was measured as a weekly average. | Baseline, Week 1, Week 2, Week 3 and Week 4 | 
| Total Amount of Rescue Medication Per Week | Total amount of rescue medication participants take per week | Baseline, Week 1, Week 2, Week 3, and Week 4 | 
| Number of Days Participants Take Rescue Medication | Number of days participants take rescue medication per week. | Baseline, Week 1, Week 2, Week 3 and Week 4 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to Adverse Events (AEs) | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. | Screening to Day 36, and Day 64 | 
| Number of Participants With Laboratory Test Values of Potential Clinical Importance | The total number of participants with laboratory test abnormalities (without regard to baseline abnormality) was assessed. Clinical laboratory tests included hematology, chemistry, urinalysis and some other tests. | Screening, Day 1, Day 15 and Day 29 | 
| Fasted Total Cholesterol Values | Percentage Change from Baseline in Fasted Total Cholesterol values | Baseline, Week 2 and Week 4 | 
| Fasted Low Density Lipoprotein (LDL) Cholesterol | Percentage Change from Baseline in LDL cholesterol Friedewald by PEG | Baseline, Week 2 and Week 4 | 
| Plasma Concentration of PF-05089771 | All participants in this group were analysed. Only plasma PK concentration of PF-05089771 was analysed. | Baseline, Week 2 and Week 4 |