Efficacy and Safety Study of ARC-4558 for Management of Pain Associated With Painful Diabetic Neuropathy

September 21, 2016 updated by: Arcion Therapeutics Inc

A Multicenter, Randomized, Double-Blind, Parallel-Group Study Comparing the Efficacy and Safety of Clonidine Topical Gel, 0.1% With Placebo in the Management of Pain Associated With Painful Diabetic Neuropathy

The purpose of this study is to determine whether ARC-4558 is effective in managing pain associated with painful diabetic neuropathy.

Study Overview

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham, School of Medicine
    • California
      • Sacramento, California, United States, 95821
        • Northern California Research
      • Santa Monica, California, United States, 90404
        • Neurological Research Institute
    • Florida
      • West Palm Beach, Florida, United States, 33401
        • Metabolic Research Institute
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Pain Treatment Center of the Bluegrass
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Health Sciences Center
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • University of Massachuetts Medical School, Division of Diabetes- Clinical Research Office
    • Nebraska
      • Omaha, Nebraska, United States, 68131
        • The Creighton Diabetes Center
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • The Center for Clinical Research
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • South Carolina
      • Murrells Inlet, South Carolina, United States, 29576
        • Waccamaw Pain Partners/Crescent Moon Research
    • Texas
      • Houston, Texas, United States, 77030
        • The Nerve and Muscle Center of Texas
      • San Antonio, Texas, United States, 78229
        • Diabetes and Glandular Disease Center
    • Virginia
      • Norfolk, Virginia, United States, 23510
        • Strelitz Diabetes Institute, Eastern Virginia Medical School
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Pain Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • has Type 1 or Type 2 diabetes mellitus
  • has a history of chronic pain attributable to a symmetrical stocking distribution neuropathy in the lower extremities for a duration of at least six months but less than or equal to five years prior to Screening

Exclusion Criteria:

  • has neuropathy secondary to non-diabetic causes
  • has a significant neurological disorder or a condition that can cause symptoms that mimic peripheral neuropathy or might confound assessment of PDN
  • has other chronic pain with intensity at or greater than the bilateral pain in the feet/toes
  • is using an implanted medical device (eg, spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for the treatment of pain
  • is pregnant or lactating

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Gel
Placebo Gel is vehicle without clonidine
TID x 12 weeks
Active Comparator: Clonidine Topical Gel (ARC-4558)
Clonidine Topical Gel contains 0.1% clonidine hydrochloride
TID x 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 12 in the Average Daily Pain NPRS (Numeric Pain Rating Scale) Score; mLOCF Imputation
Time Frame: Baseline (average of Days -7 to -1) and Week 12 (Average of Days 78 to 84)

Pain in the feet was scored daily at bedtime by the subject on a 0-10 numeric pain rating scale (NPRS) through Day 84. Subjects were asked to record average pain in the feet over the past 24 hours. A score of 0 indicated "no pain" and a score of 10 was "worst possible pain".

The change in pain is represented as Week 12 minus Baseline, so greater negative numbers represent more improvement (more pain relief).

Baseline (average of Days -7 to -1) and Week 12 (Average of Days 78 to 84)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Average Daily Pain NPRS Score for Each Week of Treatment; mLOCF Imputation
Time Frame: Baseline (average of Days -7 to -1) and Weeks 1 through 12 (weekly averages)
Pain in the feet was scored daily at bedtime by the subject on a 0-10 numeric pain rating scale (NPRS). Subjects were asked to record average pain in the feet over the past 24 hours. A score of 0 indicated "no pain" and a score of 10 was "worst possible pain". A weekly average was calculated from the daily scores for each week. The change in pain is represented as the average weekly score minus Baseline, so greater negative numbers represent more improvement (more pain relief).
Baseline (average of Days -7 to -1) and Weeks 1 through 12 (weekly averages)
Change From Baseline to Week 12 in the Worst Daily Pain NPRS Score; mLOCF Imputation
Time Frame: Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Pain in the feet was scored daily at bedtime by the subject on a 0-10 numeric pain rating scale. Subjects were asked to record the worst pain in their feet over the past 24 hours. A score of 0 indicated "no pain" and a score of 10 was "worst possible pain". The change in pain is represented as Week 12 minus Baseline, so greater negative numbers represent greater improvement (greater pain relief).
Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Percentage of Subjects Who Experience at Least 30% Reduction in Average Daily Pain From Baseline; mLOCF Imputation
Time Frame: Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Pain in the feet was scored daily at bedtime by the subject on a 0-10 numeric pain rating scale (NPRS). Subjects were asked to record average pain in the feet over the past 24 hours. A score of 0 indicated "no pain" and a score of 10 was "worst possible pain".
Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Percentage of Subjects Who Experience at Least 50% Reduction in Average Daily Pain From Baseline; mLOCF Imputation
Time Frame: Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Pain in the feet was scored daily at bedtime by the subject on a 0-10 numeric pain rating scale (NPRS). Subjects were asked to record average pain in the feet over the past 24 hours. A score of 0 indicated "no pain" and a score of 10 was "worst possible pain".
Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Change From Baseline in the Brief Pain Inventory (BPI) Severity Scale at Week 12; mLOCF Imputation
Time Frame: Baseline and Week 12
The Brief Pain Inventory was completed by the subject at clinic visits. The Severity Scale (of 0 to 40) is a composite score, which is the sum of the individual ratings for worst pain, least pain, average pain, and current pain. Each individual question is rated on a scale of 0 to 10, where 0 indicates "No Pain" and 10 indicates "Pain as bad as you can imagine". The change in pain severity is represented as Week 12 minus Baseline, so greater negative numbers represent greater improvement (pain relief).
Baseline and Week 12
Change From Baseline in the Brief Pain Inventory Functional Interference Scale at Week 12; mLOCF Imputation
Time Frame: Baseline and Week 12

The Brief Pain Inventory was completed by the subject at clinic visits. The Functional Interference Scale (of 0 to 70) is a composite score that measures the degree to which pain interferes with mood, walking, work, relationships, sleep, general activity, and enjoyment of life. The composite score is a sum of the seven individual question scores. Each individual question is rated in reference to pain over the past 24 hours on a scale of 0 to 10, where 0 indicates that pain "does not interfere" and 10 indicates that pain "completely interferes" with that function, so lower scores represent better outcomes on this scale.

The change in functional interference is represented as Week 12 minus Baseline, so greater negative numbers represent more improvement.

Baseline and Week 12
Change From Baseline to Week 12 in Overall Quality of Sleep (Chronic Pain Sleep Inventory)
Time Frame: Baseline and Week 12
Subjects rated overall quality of sleep over the past week using a 100 mm Visual Analog Scale (VAS) where 100=Excellent and 0=Very Poor. This scale was completed during clinic visits. Change from Baseline is a positive value where quality of sleep improved.
Baseline and Week 12
Change From Baseline to Week 12 in the Depression Score of the Hospital Anxiety and Depression Scale (HADS)
Time Frame: Baseline and Week 12
The HADS was completed at the Baseline and Week 12 clinic visits. The Depression Score component of the HADS includes 7 questions, each with 4 possible answer choices (rated 0 to 3). The composite score is created by adding the scores of the 7 individual questions. A score of 0 to 7 is Normal, 8-10 indicates Mild Depression, 11-14 indicates Moderate Depression, and 15-21 indicates Severe Depression. The change from Baseline is calculated as the Week 12 composite score minus the Baseline composite score.
Baseline and Week 12
Change From Baseline to Week 12 in the Anxiety Score of the Hospital Anxiety and Depression Scale (HADS)
Time Frame: Baseline and Week 12
The HADS was completed at the Baseline and Week 12 clinic visits. The Anxiety Score component of the HADS includes 7 questions, each with 4 possible answer choices (rated 0 to 3). The composite score is created by adding the scores of the 7 individual questions. A score of 0 to 7 is Normal, 8-10 indicates Mild Anxiety, 11-14 indicates Moderate Anxiety, and 15-21 indicates Severe Anxiety. The change from Baseline is calculated as the Week 12 composite score minus the Baseline composite score.
Baseline and Week 12
Change From Baseline to Week 12 in the McGill Pain Questionnaire (Short Form) Total Score
Time Frame: Baseline and Week 12
The McGill Pain Questionnaire asks subjects to rate 15 different kinds of pain, each on a scale of 0 to 3 (0=None, 1=Mild, 2=Moderate, 3=Severe). The total score is a sum of the individual ratings and has a range from 0 to 45, where higher numbers indicate more pain. The 15 types of pain assessed are throbbing, shooting, stabbing, sharp, cramping, gnawing, hot-burning, aching, heavy, tender, splitting, tiring-exhausting, sickening, fearful, and punishing-cruel. This scale was completed at the Baseline and Week 12 clinic visits. The change from Baseline is calculated as the Week 12 total score minus the Baseline total score, so greater negative numbers indicate more improvement (pain relief).
Baseline and Week 12
Patient Global Impression of Change (PGIC) at Week 12
Time Frame: Week 12
At Week 12 the subject was asked to rate their total improvement relative to Baseline, whether or not, in their judgement, it was due entirely to study drug treatment or not. Answer choices were: (+3) very much improved, (+2) much improved, (+1) minimally improved, (0) no change, (-1) minimally worse, (-2) much worse, (-3) very much worse.
Week 12
Clinician Global Impression of Change (CGIC) at Week 12
Time Frame: Week 12
At Week 12, the Investigator was asked to independently rate the subject's total improvement relative to Baseline, whether or not, in their judgement, it was due entirely to study drug treatment or not. Answer choices were: (+3) very much improved, (+2) much improved, (+1) minimally improved, (0) no change, (-1) minimally worse, (-2) much worse, (-3) very much worse.
Week 12
Change in Blood Pressure From Baseline to Week 12
Time Frame: Baseline and Week 12
Systolic and Diastolic Blood Pressure were measured at clinic visits. This outcome assesses the change in blood pressure from Baseline to Week 12 of treatment.
Baseline and Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: James N Campbell, M.D., Arcion Therapeutics Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

February 1, 2010

Study Registration Dates

First Submitted

June 10, 2008

First Submitted That Met QC Criteria

June 10, 2008

First Posted (Estimate)

June 12, 2008

Study Record Updates

Last Update Posted (Estimate)

November 8, 2016

Last Update Submitted That Met QC Criteria

September 21, 2016

Last Verified

September 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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