Clinical trial NCT01496365: Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Peripheral Neuropathy
Keywords: Keywords: pain, diabetes, neuropathy
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2011-12-21
Enrollment: 452
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Mean Change From Baseline to Week 5 in Average Daily Pain Score (ADPS) Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
Secondary outcomes:
measure: Least Square Means of Average Daily Pain Score by Week Mixed Effects Model for Repeated Measures (MMRM) Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Average Daily Pain Score Responder Rates Based on ≥30% and ≥50% Decrease From Baseline at Endpoint) Following Treatment With DS-5565 or Placebo Compared to Pregabalin
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Mean Change From Baseline to End-of-Treatment in Average Daily Sleep Interference Score Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Short-Form McGill Pain Questionnaire (SF-MPQ) Sensory and Affective Scores Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Short-Form McGill Pain Questionnaire (SF-MPQ) Total Score and Visual Analog Scale Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Short-Form McGill Pain Questionnaire (SF-MPQ) Present Pain Intensity Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Mean Change From Baseline to Endpoint of Modified Brief Pain Inventory (BPI) Subscale, Interference With Daily Functions, Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Mean Change From Baseline to Endpoint of Modified BPI Subscales, Worst, Least and Average Pain Intensity, Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Mean Change From Baseline to Endpoint of Modified BPI Subscale, Pain Right Now, Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Mean Change From Baseline to Endpoint of Modified BPI Subscale, Relief From Pain, Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Patient Global Impression of Change at End-of-Treatment or Early Termination Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: Baseline up to Week 5 postdose, up to 10 months total follow up
measure: Drug-related Treatment-Emergent Adverse Events (n ≥2 Participants in Any Treatment Group) Following Treatment With DS-5565 Compared to Pregabalin and Placebo
timeFrame: From the time of signing the informed consent form (ICF) up to 10 months postdose
Other outcomes:
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city: Renton
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city: Spokane
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state: Washington
Study officials:
affiliation: Daiichi Sankyo
name: Domenico Merante, MD
role: STUDY_DIRECTOR
References: