- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00695565
Efficacy and Safety Study of ARC-4558 for Management of Pain Associated With Painful Diabetic Neuropathy
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham, School of Medicine
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California
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Sacramento, California, United States, 95821
- Northern California Research
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Santa Monica, California, United States, 90404
- Neurological Research Institute
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Florida
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West Palm Beach, Florida, United States, 33401
- Metabolic Research Institute
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Kentucky
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Lexington, Kentucky, United States, 40503
- Pain Treatment Center of the Bluegrass
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Louisiana
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New Orleans, Louisiana, United States, 70112
- Tulane University Health Sciences Center
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Massachusetts
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Worcester, Massachusetts, United States, 01655
- University of Massachuetts Medical School, Division of Diabetes- Clinical Research Office
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Nebraska
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Omaha, Nebraska, United States, 68131
- The Creighton Diabetes Center
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New York
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Rochester, New York, United States, 14642
- University of Rochester Medical Center
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North Carolina
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Winston-Salem, North Carolina, United States, 27103
- The Center for Clinical Research
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic
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South Carolina
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Murrells Inlet, South Carolina, United States, 29576
- Waccamaw Pain Partners/Crescent Moon Research
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Texas
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Houston, Texas, United States, 77030
- The Nerve and Muscle Center of Texas
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San Antonio, Texas, United States, 78229
- Diabetes and Glandular Disease Center
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Virginia
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Norfolk, Virginia, United States, 23510
- Strelitz Diabetes Institute, Eastern Virginia Medical School
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Washington
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Seattle, Washington, United States, 98104
- Swedish Pain Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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 |
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Placebo Comparator: Placebo Gel
Placebo Gel is vehicle without clonidine
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TID x 12 weeks
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Active Comparator: Clonidine Topical Gel (ARC-4558)
Clonidine Topical Gel contains 0.1% clonidine hydrochloride
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TID x 12 weeks
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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)
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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).
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Baseline (average of Days -7 to -1) and Weeks 1 through 12 (weekly averages)
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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)
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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).
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Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
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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".
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Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
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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".
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Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
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Change From Baseline in the Brief Pain Inventory (BPI) Severity Scale at Week 12; mLOCF Imputation
Time Frame: Baseline and Week 12
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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).
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Baseline and Week 12
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Change From Baseline in the Brief Pain Inventory Functional Interference Scale at Week 12; mLOCF Imputation
Time Frame: Baseline and Week 12
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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
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Change From Baseline to Week 12 in Overall Quality of Sleep (Chronic Pain Sleep Inventory)
Time Frame: Baseline and Week 12
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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.
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Baseline and Week 12
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Change From Baseline to Week 12 in the Depression Score of the Hospital Anxiety and Depression Scale (HADS)
Time Frame: Baseline and Week 12
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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.
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Baseline and Week 12
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Change From Baseline to Week 12 in the Anxiety Score of the Hospital Anxiety and Depression Scale (HADS)
Time Frame: Baseline and Week 12
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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.
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Baseline and Week 12
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Change From Baseline to Week 12 in the McGill Pain Questionnaire (Short Form) Total Score
Time Frame: Baseline and Week 12
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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).
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Baseline and Week 12
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Patient Global Impression of Change (PGIC) at Week 12
Time Frame: Week 12
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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.
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Week 12
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Clinician Global Impression of Change (CGIC) at Week 12
Time Frame: Week 12
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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.
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Week 12
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Change in Blood Pressure From Baseline to Week 12
Time Frame: Baseline and Week 12
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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.
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Baseline and Week 12
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: James N Campbell, M.D., Arcion Therapeutics Inc
Publications and helpful links
General Publications
- Serednicki WT, Wrzosek A, Woron J, Garlicki J, Dobrogowski J, Jakowicka-Wordliczek J, Wordliczek J, Zajaczkowska R. Topical clonidine for neuropathic pain in adults. Cochrane Database Syst Rev. 2022 May 19;5(5):CD010967. doi: 10.1002/14651858.CD010967.pub3.
- Campbell CM, Kipnes MS, Stouch BC, Brady KL, Kelly M, Schmidt WK, Petersen KL, Rowbotham MC, Campbell JN. Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy. Pain. 2012 Sep;153(9):1815-1823. doi: 10.1016/j.pain.2012.04.014. Epub 2012 Jun 8.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neurologic Manifestations
- Endocrine System Diseases
- Diabetes Complications
- Diabetes Mellitus
- Neuromuscular Diseases
- Peripheral Nervous System Diseases
- Pain
- Diabetic Neuropathies
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Sympatholytics
- Clonidine
Other Study ID Numbers
- CLO-027
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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