Study to Assess Analgesic Efficacy and Safety of ASP3662 in Subjects With Painful Diabetic Peripheral Neuropathy

Study Overview
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Brief Summary
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The purpose of this study is to assess analgesic efficacy of ASP3662 relative to placebo in subjects with painful diabetic peripheral neuropathy (PDPN) as well as assess the safety and tolerability of ASP3662 relative to placebo. The analgesic effect is evaluated by measuring percent responders, change in daily worst pain score, change in average daily pain score, Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC).

Official Title
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A Phase 2a Randomized, Double-Blind, Multicenter, Placebo and Active Controlled Study to Assess Analgesic Efficacy and Safety of ASP3662 in Subjects With Painful Diabetic Peripheral Neuropathy

Conditions
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Painful Diabetic Peripheral Neuropathy (PDPN)

Intervention / Treatment
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* Drug: ASP3662
* Drug: pregabalin
* Drug: ASP3662 placebo
* Drug: pregabalin placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a BMI ≤ 40. Subject has all of the following: Established diagnosis of diabetes (Type I or II) with painful diabetic peripheral neuropathy and glycosylated hemoglobin (HgbA1c) ≤ 9.5% at Screening or Randomization. Stable diabetic drug regimen for at least 3 months prior to Screening. At least a 1 year history of PDPN. Diagnosis of PDPN to be confirmed by a score of ≥ 3 on the Michigan Neuropathy Screening Instrument (MNSI) at Screening. Subject has pain intensity score(s) ≥ 4 or ≤ 9 on an 11-point numeric pain rating scale (NPRS) at Screening Visit and prior to Randomization. Subject agrees to complete pain diaries and is complaint with the daily pain recording prior to Randomization as defined by the completion of a minimum of 5 of 7 daily pain ratings, 3 of which are required in the last 4 days. Subject's anti-diabetic regimen is anticipated to be stable throughout the study. Subject must be willing to washout of all medications currently being taken for his/her PDPN (chronic and occasional/as needed) and remain off of those pain medications while participating in the study. Exclusion Criteria: Subject has received prior treatment with pregabalin for PDPN and was considered unresponsive or intolerant. Subject has tried and failed 3 or more drugs to treat PDPN within the past 3 years. Drugs must have been administered at therapeutic doses and have been administered for an adequate period of time. Subject has a known hypersensitivity to ASP3662, pregabalin, gabapentin or acetaminophen, or their formulation components. Subject has significant pain (moderate or above) due to causes other than PDPN. Subject has a history of painful peripheral neuropathy due to a cause other than diabetes. Subject has any lower extremity amputation Subject has a current or previous foot ulcer within the past 3 months as described by medical history and/or medical examination. Subject has an active malignancy or a history of malignancy (except for treated non-melanoma skin cancer) within 5 years. Subject has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis, or a serum creatinine at Screening. Subject has creatinine clearance < 60 mL/min (estimated from serum creatinine, body weight, age, and sex using the Cockcroft and Gault equation) at Screening. Subject tests positive for hepatitis B surface antigen (HBsAg) or hepatitis C antibody at Screening or has a known history of a positive test for human immunodeficiency virus (HIV) infection. Subject has a positive drug screen for alcohol or drugs of abuse at Screening and/or Randomization. Subjects who are on low doses of benzodiazepines for sleep with a legitimate prescription will be allowed into the study. In addition, subjects with a positive drug screen at Randomization will be excluded. Subject is currently using protocol specified non-permitted medications including OTC products and is unable or does not choose to discontinue them. Subject has planned an elective surgery during planned study participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP3662<br>ASP3662 once daily (QD) and pregabalin placebo 3 times daily (TID) for Weeks 1 - 6. ASP3662 placebo QD and pregabalin placebo TID for Week 7. | Drug: ASP3662<br>* oral<br>Drug: ASP3662 placebo<br>* oral<br>Drug: pregabalin placebo<br>* oral<br>|
| Active Comparator: pregabalin<br>pregabalin TID and ASP3662 placebo QD for Weeks 1 - 7. | Drug: pregabalin<br>* oral<br>Drug: ASP3662 placebo<br>* oral<br>|
| Placebo Comparator: Placebo<br>ASP3662 placebo QD and pregabalin placebo TID for Weeks 1 - 7. | Drug: ASP3662 placebo<br>* oral<br>Drug: pregabalin placebo<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in mean 24-hour average pain intensity as reported on the NPRS | Numerical Pain Rating Scale (NPRS) | Baseline to Week 6/ End of Treatment (EOT) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders in mean 24-hour average pain intensity score |  | Baseline to Week 6/ EOT | 
| Change from Baseline in mean of 24-hour average pain intensity score |  | Baseline to Weeks 1, 2, 3, 4, 5 and 6 | 
| Change from Baseline in mean daily worst pain score |  | Baseline to Week 6/ EOT | 
| Change from Baseline in mean daily average pain score |  | Baseline to Week 6/ EOT | 
| Patient Global Impression Change (PGIC) |  | Week 6/ EOT | 
| Clinical Global Impression of Change (CGIC) |  | Week 6/ EOT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Painful diabetic peripheral neuropathy (PDPN), ASP3662