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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01928381
First received: August 21, 2013
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Diabetic Neuropathy, Painful; Diabetic Neuropathies
Drug: AZD5213 + pregabalin
Drug: Placebo
Drug: pregabalin capsules
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change in Item 5 of Brief Pain Inventory Diabetic Peripheral Neuropathy version (BPI-DPN) [ Time Frame: average calculated over the last 3 days of each crossover ] [ Designated as safety issue: No ]
    This will be analyzed using a mixed linear model with " subject" as a random main effect factor, "period" as fixed main effect factor with three levels of "treament" as a fixed main effect factor with 3 levels.


Secondary Outcome Measures:
  • Incidence and severity of Treatment Emergent Adverse Events [ Time Frame: Days 1-28: Part 1; Days 29-128: Part 2 ] [ Designated as safety issue: Yes ]
    Incidence and severity of adverse events will be summarized separately for Part 1 and Part, as applicable

  • Vital signs ( blood pressure, heart rate, weight and temperature) [ Time Frame: Days 1-28: Part 1; Days 29-128: Part 2 ] [ Designated as safety issue: Yes ]
    Changes in vital signs will be summarized separately for Part 1 and Part 2, as applicable

  • Clinical Laboratory Evaluations [ Time Frame: Days 1-28: Part 1; Days 29-128: Part 2 ] [ Designated as safety issue: Yes ]
    Changes in clinical laboratory evaluations will be summarized separately for Part 1 and Part 2, as applicable

  • Medical Outcomes Study (Revised) Sleep Scale (MOS-R) [ Time Frame: Days 29-128: Part 2 ] [ Designated as safety issue: Yes ]
    Changes in sleep quality will be summarized for Part 2 of the study

  • Columbia Suicide Severity Rating Scale (CSSR-S) [ Time Frame: Days 1-28: Part 1; Days 29-128: Part 2 ] [ Designated as safety issue: Yes ]
    Changes in the CSSR-S will be summarized separately for Part 1 and Part 2, as applicable

  • Neuropathic Pain Symptom Inventory (NPSI) [ Time Frame: Days 29-128: Part 2 ] [ Designated as safety issue: No ]
    Changes in NPSI ratings will be summarized for Part 2 of the study

  • Sleep Interference Scale (SIS) [ Time Frame: Days 29-128: Part 2 ] [ Designated as safety issue: Yes ]
    Changes in SIS ratings will be summarized for Part 2 of the study


Other Outcome Measures:
  • Change in Items 3,4,6, and 7 of the BPI-DPN [ Time Frame: Days 29-128: Part 2 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: November 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo capsules
Capsules to match pregabalin and AZD5213
Drug: Placebo
Double blind placebo capsules to match AZD5213 and pregabalin
Experimental: AZD5213 + pregabalin
AZD5213 in combination with pregabalin
Drug: AZD5213 + pregabalin
Double blind Investigational drug AZD5213 (capsules) given in combination with pregabalin (capsules)
Other Name: pregabalin (LYRICA)
Active Comparator: pregabalin
pregabalin capsules
Drug: pregabalin capsules
Double blind pregabalin capsules to match AZD5213 and placebo
Other Name: LYRICA (pregabalin)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).

  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: NCT01928381

Contacts
Contact: Clinical Trial Transparency ClinicalTrialTransparency@astrazeneca.com
Contact: Anne Macek, MD 610-296-1574 anne.macek@theoremclinical.com

Locations
United States, Massachusetts
Research Site Recruiting
Brockton, Massachusetts, United States
Research Site Recruiting
Natick, Massachusetts, United States
Research Site Recruiting
Watertown, Massachusetts, United States
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01928381     History of Changes
Other Study ID Numbers: D3031C00001
Study First Received: August 21, 2013
Last Updated: March 28, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetic Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Pregabalin
Gamma-Aminobutyric Acid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
GABA Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on October 01, 2014