Diabetic Peripheral Neuropathic Pain (DPNP)

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)

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).

Study Overview

• Status: Completed
• Conditions: Diabetic Peripheral Neuropathic Pain
• Intervention / Treatment: Drug: Pregabalin; Drug: BMS-954561; Drug: Placebo matching BMS-954561; Drug: Placebo matching Pregabalin

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Dijon Cedex, France, 21079
    • Local Institution
  • Nantes Cedex 1, France, 44093
    • Local Institution
  • Nice Cedex 1, France, 06003
    • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • California
    • Lomita, California, United States, 90717
      • Torrance Clinical Research
    • Los Gatos, California, United States, 95032
      • Office Of Richard S. Cherlin, Md
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • St Petersburg, Florida, United States, 33716
      • Comprehensive Clinical Development, Inc.
  • Illinois
    • Lake Barrington, Illinois, United States, 60010
      • Northwest Neurology Ltd.
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth Biomedical Research, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center For Pharmaceutical Research. Pc
    • St. Louis, Missouri, United States, 63141
      • Mercy Health Research
  • New York
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physicians East P.A.
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Ohio
    • Akron, Ohio, United States, 44311
      • Radiant Research, Inc.
    • Toledo, Ohio, United States, 43623
      • Neurology & Neuroscience Center Of Ohio
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes & Endocrine Center
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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)	Drug: BMS-954561; Drug: Placebo matching BMS-954561
Other: 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)	Drug: BMS-954561; Drug: Placebo matching BMS-954561
Other: Arm 3: Pregabalin 100mg; Pregabalin 100mg TID to Placebo OR Placebo to 100mg TID Active to Placebo or Placebo to Active (cross-over)	Drug: Pregabalin; Drug: Placebo matching Pregabalin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: February 11, 2011
• First Submitted That Met QC Criteria: March 11, 2011
• First Posted (Estimate): March 14, 2011

Study Record Updates

• Last Update Posted (Estimate): December 7, 2015
• Last Update Submitted That Met QC Criteria: November 6, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: CN169-001; 2010-023042-70 (EudraCT Number)