Safety, Tolerability and Preliminary Efficacy of AZD5213 in Combination With Pregabalin in Subjects With PDN and Good Pain Reporting Ability

Study Overview
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Brief Summary
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This is a 2-part study. In Part 1 of the study, subjects will undergo a pain reporting training program in which a painful stimulus will be applied to the subject's hand, and the subjects will be asked to report how painful the stimulus is. Over the course of the pain training sessions, feedback will be provided to the subject about how accurately they are reporting their degree of pain, relative to the amount of pressure stimulus applied to evoke pain. Those subjects who have adequate pain reporting ability will be asked to continue into Part 2 of the study in which 3 different blinded study drugs will be administered to each subject, in a crossover design to compare whether or not the study drugs improve pain associated with diabetic neuropathy.

Detailed Description
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This is a multi-center, randomized, two-part study in adults (ages 18-75 years) with Painful Diabetic Neuropathy (PDN). In Part 1 of the study, eligible subjects will enter a 4-week Pain Training Period. During the Pain Training Period, subjects will receive three weekly in-clinic training sessions using repeated rating of experimental pressure pain stimuli. Subjects will receive feedback during this training and will be evaluated on their pain-reporting ability during each in-clinic session. Subjects with acceptable pain-reporting ability at the conclusion of the Pain Training Period will be eligible to enter Part 2 of the study. Subjects with unacceptable pain-reporting ability at the conclusion of the Pain Training Period will be discontinued from the study. Part 2 of the study will consist of three consecutive double-blind crossover periods. Each crossover period will include 31 days of double-blind treatment. A follow-up visit will occur 14 ± 7 days after the last dose of study medication. One of three treatments (placebo, pregabalin, or pregabalin + AZD5213) will be administered during each crossover treatment period, as determined by a randomly assigned treatment sequence. Approximately 65 subjects will be screened in Part 1 of the study, in order to randomize up to approximately 32 subjects in Part 2 of the study.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Crossover Study to Evaluate the Preliminary Efficacy of AZD5213 in Combination With Pregabalin in Subjects With Painful Diabetic Neuropathy and Good Pain Reporting Ability

Conditions
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Diabetic Neuropathy, Painful; Diabetic Neuropathies

Intervention / Treatment
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* Drug: AZD5213 + pregabalin
* Drug: Placebo
* Drug: pregabalin capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Male or female, age 18 to 75 years, inclusive, at Screen. 2. Subjects must provide informed consent in accordance with local regulations before the conduct of any study-related procedures. The informed consent should reflect the protocol stipulations concerning the use of contraception. 3. Diagnosis of Type 1 or Type 2 diabetes mellitus for at least 1 year prior to Screen. 4. Diabetes-related painful neuropathy for at least 6 months prior to Screen. 5. Pain that began in the feet and is symmetric or nearly symmetric. 6. Diabetes has been clinically stable for at least 2 months prior to Screen, and between Screen and baseline (Day 35). 7. At Screen and baseline, score of at least 4 on Item 5 (average pain) of the modified Brief Pain Inventory for patients with painful diabetic peripheral neuropathy (BPI-DPN). 8. Able to participate in all scheduled evaluations and to complete all required tests and procedures. 9. In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study. Exclusion Criteria: 1. Known or suspected hypersensitivity to pregabalin. 2. Clinically important illness or infection (e.g., chronic, persistent, or acute infection) within 30 days prior to screen or between screen adn baseline. 3. Presence of any psychiatric or neurologic disorder or any other disorder or symptom, if, in the judgement of the investigator, the disorder or symptom is likely to confound interpretation of drug effect or affect the subject's ability to complete the study. Any clinically important abnormality, as determined by investigator at Screen or baseline, in physical or neurologic examination, vital sign, ECG, or clinical laboratory test results that could be detrimental to the subject, or could affect the subject's ability to complete the study. 4. Initiation or change in intensity or frequency of non-pharmacologic therapy for PDN, including psychotherapy, physical therapy, massage, acupuncture, acupressure, or chiropractic care, within 3 months prior to baseline).

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo capsules<br>Capsules to match pregabalin and AZD5213 | Drug: Placebo<br>* Double blind placebo capsules to match AZD5213 and pregabalin<br>|
| Experimental: AZD5213 + pregabalin<br>AZD5213 in combination with pregabalin | Drug: AZD5213 + pregabalin<br>* Double blind Investigational drug AZD5213 (capsules) given in combination with pregabalin (capsules)<br>* Other names: pregabalin (LYRICA);|
| Active Comparator: pregabalin<br>pregabalin capsules | Drug: pregabalin capsules<br>* Double blind pregabalin capsules to match AZD5213 and placebo<br>* Other names: LYRICA (pregabalin);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Index - Item 5, Average Daily Pain Score (Range 0-10) Higher Values Indicate Worse Pain | Brief pain Index - diabetic painful neuropathy (BPI-DPN) - average daily pain, Item 5 (final 2 day diary + in clinic assessment at end of 3 week treatment period) | 3 weeks of treatment |