Diabetic Peripheral Neuropathic Pain (DPNP)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy of study drug (BMS-954561) as compared to placebo in the treatment of patients with diabetic peripheral neuropathic pain (DPNP).

Detailed Description
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Allocation: Randomized Stratified; Intervention Model: Cross-over Versus Comparator + Placebo

Official Title
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A Randomized, Multicenter, Double-blind, Placebo and Active-controlled, Cross-over Study of the Efficacy and Safety of BMS-954561 in Patients With Diabetic Peripheral Neuropathic Pain (DPNP)

Conditions
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Diabetic Peripheral Neuropathic Pain

Intervention / Treatment
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* Drug: BMS-954561
* Drug: Pregabalin
* Drug: Placebo matching BMS-954561
* Drug: Placebo matching Pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type I or Type II diabetes with painful, distal, symmetrical, sensory-motor neuropathy attributed to diabetes, of at least 6 months duration. Score of ≥3 on Michigan Neuropathy Screening Instrument The patient is able to satisfactorily complete, in the Investigator's judgment, the Cognitive Battery. Based on patient diary information collected during the Screening/Baseline period, the patient has completed at least 5 of 7 daily diary entries and has an average weekly pain rating of at least 4 on the 11-point pain rating scale, in the week immediately prior to randomization (Baseline Visit). Male or female, 18-85 years of age. Exclusion Criteria: History of complete lack of response to Pregabalin (at least 300 mg qd for 4 weeks) or Gabapentin (at least 1800 mg qd for 4 weeks). Other severe pain that may potentially confound pain assessment. Hemoglobin A1c > 9% Hemoglobin ≤ 9 g/dL Estimated glomerular filtration rate (eGFR) according to the re-expressed abbreviated (four-variable) Modification of Diet in Renal Disease (MDRD) Study equation ≤ 50ml/min/1.73m2 Patients who have been on a stable dose of anticonvulsant, anticholinergic, diabetic meds, nicotine replacements, or any other smoking cessation meds for <4 weeks prior to randomization. Patients who are on stable doses for ≥ 4 weeks prior to randomization are allowed, however, there should be no adjustments to the dose of these medications during study. Patients currently on more than one drug for treatment of neuropathic pain (low dose opioids or antidepressants). Patients are allowed to participate if on a stable dose of for at least 4 weeks prior to randomization (Day1) and should remain stable during study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm 1: BMS-954561 40mg or 80mg<br>BMS-954561 40mg or 80mg TID to Placebo OR Placebo to 40mg or 80mg TID Active to Placebo or Placebo to Active (cross-over) | Drug: BMS-954561<br> <br> Drug: Placebo matching BMS-954561<br> <br> |
| Other: Arm 2: BMS-954561 150mg or 300mg<br>BMS-954561 150mg or 300mg TID to Placebo OR Placebo to 150mg or 300mg TID Active to Placebo or Placebo to Active (cross-over) | Drug: BMS-954561<br> <br> Drug: Placebo matching BMS-954561<br> <br> |
| Other: Arm 3: Pregabalin 100mg<br>Pregabalin 100mg TID to Placebo OR Placebo to 100mg TID Active to Placebo or Placebo to Active (cross-over) | Drug: Pregabalin<br> <br> Drug: Placebo matching Pregabalin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of this study is the average pain score for BMS-954561 vs. placebo. |  | Up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Screening/Baseline Phase: Baseline | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 1 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 2 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 3 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 4 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 5 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 6 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 7 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 8 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 9 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Double-blind Treatment Phase: Week 10 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Open-Label Phase: Week 2 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Open-Label Phase: Week 4 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Open-Label Phase: Week 8 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Open-Label Phase: Week 12 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Open-Label Phase: Week 16 | 
| Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). |  | Open-Label Phase: Week 20 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 1 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 2 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 3 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 4 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 5 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 6 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 7 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 8 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 9 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Double-blind Treatment Phase: Week 10 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Open-Label Phase: Week 2 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Open-Label Phase: Week 4 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Open-Label Phase: Week 8 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Open-Label Phase: Week 12 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Open-Label Phase: Week 16 | 
| Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. |  | Open-Label Phase: Week 20 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Screening/Baseline Phase: Baseline | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 1 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 2 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 3 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 4 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 5 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 6 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 7 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 8 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 9 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Double-blind Treatment Phase: Week 10 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Open-Label Phase: Week 2 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Open-Label Phase: Week 4 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Open-Label Phase: Week 8 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Open-Label Phase: Week 12 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Open-Label Phase: Week 16 | 
| Evaluate the tolerability and safety of BMS-954561 in patients with DPNP as measured by the frequency and severity of adverse events, frequency of severe adverse events, and discontinuations due to adverse events. |  | Open-Label Phase: Week 20 |