Diabetic Peripheral Neuropathic Pain (DPNP)

• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Screening/Baseline Phase: Baseline ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 1 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 2 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 3 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 4 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 5 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 6 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 7 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 8 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 9 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Double-blind Treatment Phase: Week 10 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Open-Label Phase: Week 2 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Open-Label Phase: Week 4 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Open-Label Phase: Week 8 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Open-Label Phase: Week 12 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Open-Label Phase: Week 16 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo using the Brief Pain Inventory-short form (BPI-SF). [ Time Frame: Open-Label Phase: Week 20 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 1 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 2 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 3 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 4 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 5 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 6 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 7 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 8 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 9 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Double-blind Treatment Phase: Week 10 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Open-Label Phase: Week 2 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Open-Label Phase: Week 4 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Open-Label Phase: Week 8 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Open-Label Phase: Week 12 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Open-Label Phase: Week 16 ] [ Designated as safety issue: No ]
• Evaluate the effect of BMS-954561 compared to placebo, on the Patient Global Impression of Change (PGIC) scale. [ Time Frame: Open-Label Phase: Week 20 ] [ Designated as safety issue: No ]
• 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. [ Time Frame: Screening/Baseline Phase: Baseline ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 1 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 2 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 3 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 4 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 5 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 6 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 7 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 8 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 9 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Double-blind Treatment Phase: Week 10 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Open-Label Phase: Week 2 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Open-Label Phase: Week 4 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Open-Label Phase: Week 8 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Open-Label Phase: Week 12 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Open-Label Phase: Week 16 ] [ Designated as safety issue: Yes ]
• 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. [ Time Frame: Open-Label Phase: Week 20 ] [ Designated as safety issue: Yes ]

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).

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

• Drug: BMS-954561
  Capsule, Oral, 40mg or 80mg, Three times daily (TID), 10 weeks (double-blind) + 20 weeks (open-label BMS-954561)
  Other Name: BMS-954561
• Drug: Pregabalin
  Capsule, Oral, 100mg, Three times daily (TID), 10 weeks (double-blind) + 20 weeks (open-label BMS-954561)
  Other Name: Lyrica in double-blind + BMS-954561 in open-label
• Drug: BMS-954561
  Capsule, Oral, 150mg or 300mg, Three times daily (TID), 10 weeks (double-blind) + 20 weeks (open-label BMS-954561)
  Other Name: BMS-954561
• Drug: Placebo matching BMS-954561
  Capsule, Oral, 0mg, Three times daily (TID)
• Drug: Placebo matching Pregabalin
  Capsule, Oral, 0mg, Three times daily (TID), 10 weeks (double-blind) + 20 weeks (open-label BMS-954561)

• Arm 1: BMS-954561 40mg or 80mg

  BMS-954561 40mg or 80mg TID to Placebo OR Placebo to 40mg or 80mg TID

  Active to Placebo or Placebo to Active (cross-over)

  Interventions:

  • Drug: BMS-954561
  • Drug: Placebo matching BMS-954561
• Arm 2: BMS-954561 150mg or 300mg

  BMS-954561 150mg or 300mg TID to Placebo OR Placebo to 150mg or 300mg TID

  Active to Placebo or Placebo to Active (cross-over)

  Interventions:

  • Drug: BMS-954561
  • Drug: Placebo matching BMS-954561
• Arm 3: Pregabalin 100mg

  Pregabalin 100mg TID to Placebo OR Placebo to 100mg TID

  Active to Placebo or Placebo to Active (cross-over)

  Interventions:

  • Drug: Pregabalin
  • Drug: Placebo matching Pregabalin

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.