Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01496365
First received: December 19, 2011
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Diabetic Peripheral Neuropathy
Drug: DS-5565 tablet
Drug: pregabalin capsule
Drug: Placebo tablet
Drug: placebo capsule
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Change from baseline in average daily pain score [ Time Frame: baseline and week 5 ] [ Designated as safety issue: No ]
    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:
  • To characterize the dose-response of DS 5565 on change from baseline in ADPS [ Time Frame: baseline and Week 5 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 452
Study Start Date: November 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01496365

  Show 78 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
Investigators
Study Director: Domenico Merante, MD Daiichi Sankyo Inc.
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01496365     History of Changes
Other Study ID Numbers: DS5565-A-U201
Study First Received: December 19, 2011
Last Updated: March 10, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Neuralgia
Peripheral Nervous System Diseases
Demyelinating Diseases
Polyneuropathies
Nerve Compression Syndromes
Neurologic Manifestations
Neurotoxicity Syndromes
Diabetic Neuropathies
Pain
Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Poisoning
Substance-Related Disorders
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Pregabalin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants

ClinicalTrials.gov processed this record on July 24, 2014