Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

Study Description

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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

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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
Actual Primary Completion Date :	January 2013
Actual Study Completion Date :	January 2013

Arms and Interventions

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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

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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

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 78 Study Locations

Sponsors and Collaborators

Daiichi Sankyo, Inc.

Investigators

Study Director:	Domenico Merante, MD	Daiichi Sankyo, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations 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
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; Neuralgia; Diabetic Neuropathies; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Pregabalin	Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs