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Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

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ClinicalTrials.gov Identifier: NCT01496365
Recruitment Status : Completed
First Posted : December 21, 2011
Last Update Posted : April 7, 2014
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this study is to evaluate the safety, tolerability and effectiveness of DS-5565 compared to placebo (inactive substance) and pregabalin in diabetic subjects with DPN.

Condition or disease Intervention/treatment Phase
Diabetic Peripheral Neuropathy Drug: DS-5565 tablet Drug: pregabalin capsule Drug: Placebo tablet Drug: placebo capsule Phase 2

Detailed Description:

Diabetic peripheral neuropathy (DPN) affects up to 50% of patients who have diabetes for at least 25 years. Up to 26% of all patients with DPN experience neuropathic pain. DPN pain contributes to sleep disorders, depression, and anxiety, which together may have an impact on a patient's well-being and quality of life.

There are currently several drugs used to treat painful DPN. For example, Lyrica® (pregabalin) is approved by the United States Food and Drug Administration (FDA) to treat neuropathic pain associated with DPN and is commonly prescribed. The dosage of the FDA-approved drugs is limited by side-effects such as dizziness, sleepiness, weight gain and swelling of the hands, legs, and feet. As a result, many patients suffering from DPN pain do not get satisfactory pain relief.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 452 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo and Active Comparator-Controlled Study of DS-5565 for Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Study Start Date : November 2011
Primary Completion Date : January 2013
Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Pregabalin
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: DS-5565 5mg nighttime
DS-5565 5 mg/day (one 5 mg tablet at bedtime)
Drug: DS-5565 tablet
5mg and 10mg tablets
Drug: placebo capsule
Other Name: placebo capsule matching over-encapsulated pregabalin
Experimental: DS-5565 10 mg at bedtime
DS-5565 10 mg/day (one 10 mg tablet at bedtime)
Drug: DS-5565 tablet
5mg and 10mg tablets
Drug: placebo capsule
Other Name: placebo capsule matching over-encapsulated pregabalin
Experimental: DS-5565 15 mg at bedtime
DS-5565 15 mg/day (one 5 mg tablet plus one 10 mg tablet at bedtime)
Drug: DS-5565 tablet
5mg and 10mg tablets
Drug: placebo capsule
Other Name: placebo capsule matching over-encapsulated pregabalin
Experimental: DS-5565 20 mg total per day
DS-5565 20 mg/day (one 10 mg tablet in the morning and one 10 mg tablet at bedtime)
Drug: DS-5565 tablet
5mg and 10mg tablets
Drug: placebo capsule
Other Name: placebo capsule matching over-encapsulated pregabalin
Experimental: DS-5565 30 mg total per day
DS-5565 30 mg/day (one 5 mg tablet plus one 10 mg tablet in the morning and one 5 mg tablet plus one 10 mg tablet at bedtime)
Drug: DS-5565 tablet
5mg and 10mg tablets
Drug: placebo capsule
Other Name: placebo capsule matching over-encapsulated pregabalin
Active Comparator: Pregabalin 300 mg total per day
Pregabalin 300 mg/day (two 150 mg capsules, in the morning and at bedtime)
Drug: pregabalin capsule
75mg and 150mg over-encapsulated
Other Name: Lyrica
Drug: Placebo tablet
Other Name: placebo tablet matching DS-5565 tablet

Outcome Measures

Primary Outcome Measures :
  1. Change from baseline in average daily pain score [ Time Frame: baseline and week 5 ]
    Change from baseline in subject with DPN pain (a minimally meaningful effect is a decrease of at least 1.0 point [scale of 0 to 10] versus placebo).

Secondary Outcome Measures :
  1. To characterize the dose-response of DS 5565 on change from baseline in ADPS [ Time Frame: baseline and Week 5 ]
  2. To assess the incidence of responders, by treatment group, based on the proportion of subjects achieving a ≥ 30% or ≥ 50% reduction from baseline in ADPS [ Time Frame: Week 5 ]
  3. To compare the effects of DS-5565 versus pregabalin (titrated to 300 mg/day) based on change from baseline in ADPS and responder rate [ Time Frame: baseline and Week 5 ]
  4. To assess the effects of DS-5565 on pain intensity, severity and interference using the Short-Form McGill Pain Questionnaire (SF-MPQ) and modified Brief Pain Inventory (BPI) instruments [ Time Frame: Weeks 1, 2, 3, 4, 5 ]
  5. To assess the effects of DS-5565 on PGIC, pain-associated sleep interference, anxiety and depression, and quality of life, using standardized instruments [ Time Frame: Weeks 1, 2, 3, 4, 5 ]
  6. To characterize the safety and tolerability of DS 5565 based on the overall incidence of specific AEs of interest (CNS-related AEs such as dizziness and somnolence [ Time Frame: Week 5 ]
  7. To characterize the exposure-response relationships of DS-5565 to change from baseline in ADPS and to specific AEs of interest (eg, dizziness and somnolence) [ Time Frame: Week 5 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age > 18 years of age
  2. Able to give informed consent and willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
  3. Type 1 or type 2 diabetes with a hemoglobin A1c (HbA1c) ≤ 10% at Screening and on a stable antidiabetic medication regimen for at least 30 days prior to Screening (insulin therapy is acceptable)
  4. Painful distal symmetrical sensorimotor polyneuropathy (as per American Society of Pain Educators guidelines ) diagnosed for at least 6 months, based on neurological history and/or examination; diagnosis includes absent or reduced deep tendon reflexes at both ankles
  5. At Screening, a pain score of ≥ 40 mm on the SF-MPQ VAS
  6. At Randomization, a pain score of ≥ 40 mm on the SF-MPQ VAS and an ADPS of ≥ 4 on the 11-point NRS, the latter calculated from a minimum of 4 pain ratings in daily diaries obtained during the 1-week Baseline Period (prior to randomization)
  7. Creatinine clearance > 60 mL/min (estimated using the Cockcroft-Gault equation)
  8. Antidiabetic and other medications anticipated to remain stable and constant during the study period
  9. Women of child bearing potential (WOCBP) must be using an adequate method of contraception as detailed in the protocol to avoid pregnancy during the study and for 4 weeks after study completion

Exclusion Criteria:

  1. Diagnosis of mononeuropathy
  2. Use of concomitant medications that may confound assessments of efficacy and/or safety (see Section 5.2)
  3. Major psychiatric disorders
  4. Have had a malignancy other than basal cell carcinoma within the past 2 years
  5. At Visit 1, have a white blood cell count < 2500/mm3, neutrophil count < 1500/mm3, or platelet count < 100 x 103/mm3
  6. Clinically significant unstable diabetes mellitus, unstable hepatic, respiratory, or hematologic illness, unstable cardiovascular disease (including myocardial infarction in the 3 months prior to Visit 1), or symptomatic peripheral vascular disease
  7. Clinically significant findings on the Screening ECG
  8. History of pernicious anemia, untreated hypothyroidism, chronic hepatitis B, hepatitis B within the past 3 months, or human immunodeficiency virus infection
  9. Amputations of body parts other than toes
  10. Prior therapeutic failure of pregabalin or gabapentin (considered unresponsive or intolerant to treatment); therapeutic failure implies lack of efficacy following full titration to effective doses (eg, 300 mg/day for pregabalin)
  11. Known hypersensitivity to pregabalin or gabapentin
  12. Requirement for concomitant anticonvulsant and antidepressant therapy, with the exception of stable doses of SSRIs
  13. Neurologic disorders unrelated to DPN that may confound the assessment of pain associated with DPN
  14. Skin conditions that could alter sensation
  15. Other sources of pain that may confound assessment or self-evaluation of the pain due to DPN
  16. Abuse of prescription medications, street drugs or alcohol (including alcohol dependence) within the last 1 year
  17. Current enrollment in another investigational study, participation in another investigational study with the past 30 days, or other current or recent use of any investigational drug
  18. Pregnancy (as based on lab test results) or breast feeding
  19. Laboratory values exceeding limits listed in Table 4.1 of the protocol
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01496365

  Hide Study Locations
United States, Alabama
Birmingham, Alabama, United States, 35242
Huntsville, Alabama, United States, 35801
United States, Arizona
Mesa, Arizona, United States, 85206
Phoenix, Arizona, United States, 85023
Phoenix, Arizona, United States, 85028
Tucson, Arizona, United States, 85712
United States, Arkansas
Hot Springs, Arkansas, United States, 71913
Little Rock, Arkansas, United States, 72205
United States, California
Buena Park, California, United States, 90620
Burbank, California, United States, 91505
Chino, California, United States, 91710
Fresno, California, United States, 93726
Huntington Beach, California, United States, 92648
Lakewood, California, United States, 90712
Lomita, California, United States, 90717
Long Beach, California, United States, 90806
Santa Monica, California, United States, 90404
Walnut Creek, California, United States, 94598
United States, Colorado
Boulder, Colorado, United States, 80304
Colorado Springs, Colorado, United States, 80920
Denver, Colorado, United States, 80209
Golden, Colorado, United States, 80401
United States, Connecticut
Cromwell, Connecticut, United States, 06416
Fairfield, Connecticut, United States, 06824
United States, Florida
Bradenton, Florida, United States, 34208
Brooksville, Florida, United States, 34601
Clearwater, Florida, United States, 33756
Hallandale Beach, Florida, United States, 33009
Miami, Florida, United States, 33143
Miami, Florida, United States, 33169
New Port Richey, Florida, United States, 34217
New Port Richey, Florida, United States, 34652
Orlando, Florida, United States, 32806
Sunrise, Florida, United States, 33351
United States, Georgia
Columbus, Georgia, United States, 31909
Gainesville, Georgia, United States, 30501
Marietta, Georgia, United States, 30060
United States, Indiana
Evansville, Indiana, United States, 44714
United States, Kentucky
Madisonville, Kentucky, United States, 42431
Paducah, Kentucky, United States, 42003
United States, Maryland
Hyattsville, Maryland, United States, 20782
United States, Massachusetts
Brockton, Massachusetts, United States, 02301
United States, Michigan
Farmington Hills, Michigan, United States, 48025
United States, Mississippi
Olive Branch, Mississippi, United States, 38654
United States, Missouri
Florissant, Missouri, United States, 63031
Kansas City, Missouri, United States, 64114
St. Louis, Missouri, United States, 63141
United States, Nebraska
Omaha, Nebraska, United States, 68131
United States, Nevada
Las Vegas, Nevada, United States, 89106
Las Vegas, Nevada, United States, 89119
Las Vegas, Nevada, United States, 89123
United States, New York
Albany, New York, United States, 12205
United States, Ohio
Cincinnati, Ohio, United States, 45245
Dayton, Ohio, United States, 45439
Toledo, Ohio, United States, 43623
United States, Oklahoma
Tulsa, Oklahoma, United States, 74104
United States, Pennsylvania
Duncansville, Pennsylvania, United States, 16635
Greensburg, Pennsylvania, United States, 15601
United States, Rhode Island
Warwick, Rhode Island, United States, 02886
United States, South Carolina
Charleston, South Carolina, United States, 29407
Greer, South Carolina, United States, 29561
Greer, South Carolina, United States, 29651
Mt. Pleasant, South Carolina, United States, 29464
United States, Tennessee
Chattanooga, Tennessee, United States, 37411
United States, Texas
Austin, Texas, United States, 78731
Dallas, Texas, United States, 75230
Dallas, Texas, United States, 75231
El Paso, Texas, United States, 79925
Houston, Texas, United States, 77030
San Antonio, Texas, United States, 78154
San Antonio, Texas, United States, 78229
Sugarland, Texas, United States, 77478
United States, Virginia
Norfolk, Virginia, United States, 23507
Norfolk, Virginia, United States, 23510
Richmond, Virginia, United States, 23249
Virginia Beach, Virginia, United States, 23454
United States, Washington
Renton, Washington, United States, 98057
Spokane, Washington, United States, 99207
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Study Director: Domenico Merante, MD Daiichi Sankyo, Inc.
More Information

Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT01496365     History of Changes
Other Study ID Numbers: DS5565-A-U201
First Posted: December 21, 2011    Key Record Dates
Last Update Posted: April 7, 2014
Last Verified: March 2014

Keywords provided by Daiichi Sankyo, Inc.:
Keywords: pain, diabetes, neuropathy

Additional relevant MeSH terms:
Peripheral Nervous System Diseases
Diabetic Neuropathies
Neuromuscular Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs