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

Phase 2
Completed
Conditions
Painful Diabetic Neuropathy
Interventions
Registration Number
NCT00695565
Lead Sponsor
Arcion Therapeutics Inc
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
180
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Clonidine Topical Gel (ARC-4558)Clonidine Topical Gel (ARC-4558)Clonidine Topical Gel contains 0.1% clonidine hydrochloride
Placebo GelPlacebo GelPlacebo Gel is vehicle without clonidine
Primary Outcome Measures
NameTimeMethod
Change From Baseline to Week 12 in the Average Daily Pain NPRS (Numeric Pain Rating Scale) Score; mLOCF ImputationBaseline (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).

Secondary Outcome Measures
NameTimeMethod
Change From Baseline to Week 12 in the Depression Score of the Hospital Anxiety and Depression Scale (HADS)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.

Patient Global Impression of Change (PGIC) at Week 12Week 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.

Percentage of Subjects Who Experience at Least 30% Reduction in Average Daily Pain From Baseline; mLOCF ImputationBaseline (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".

Change From Baseline to Week 12 in the McGill Pain Questionnaire (Short Form) Total ScoreBaseline 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).

Change in Blood Pressure From Baseline to Week 12Baseline 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.

Change From Baseline in the Brief Pain Inventory (BPI) Severity Scale at Week 12; mLOCF ImputationBaseline 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).

Change From Baseline to Week 12 in Overall Quality of Sleep (Chronic Pain Sleep Inventory)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.

Change From Baseline to Week 12 in the Worst Daily Pain NPRS Score; mLOCF ImputationBaseline (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).

Change From Baseline in the Brief Pain Inventory Functional Interference Scale at Week 12; mLOCF ImputationBaseline 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.

Clinician Global Impression of Change (CGIC) at Week 12Week 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.

Change From Baseline in Average Daily Pain NPRS Score for Each Week of Treatment; mLOCF ImputationBaseline (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).

Percentage of Subjects Who Experience at Least 50% Reduction in Average Daily Pain From Baseline; mLOCF ImputationBaseline (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".

Change From Baseline to Week 12 in the Anxiety Score of the Hospital Anxiety and Depression Scale (HADS)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.

Trial Locations

Locations (16)

Pain Treatment Center of the Bluegrass

🇺🇸

Lexington, Kentucky, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

The Nerve and Muscle Center of Texas

🇺🇸

Houston, Texas, United States

Metabolic Research Institute

🇺🇸

West Palm Beach, Florida, United States

University of Massachuetts Medical School, Division of Diabetes- Clinical Research Office

🇺🇸

Worcester, Massachusetts, United States

Neurological Research Institute

🇺🇸

Santa Monica, California, United States

University of Rochester Medical Center

🇺🇸

Rochester, New York, United States

The Center for Clinical Research

🇺🇸

Winston-Salem, North Carolina, United States

Northern California Research

🇺🇸

Sacramento, California, United States

Strelitz Diabetes Institute, Eastern Virginia Medical School

🇺🇸

Norfolk, Virginia, United States

University of Alabama at Birmingham, School of Medicine

🇺🇸

Birmingham, Alabama, United States

Diabetes and Glandular Disease Center

🇺🇸

San Antonio, Texas, United States

Swedish Pain Center

🇺🇸

Seattle, Washington, United States

Tulane University Health Sciences Center

🇺🇸

New Orleans, Louisiana, United States

The Creighton Diabetes Center

🇺🇸

Omaha, Nebraska, United States

Waccamaw Pain Partners/Crescent Moon Research

🇺🇸

Murrells Inlet, South Carolina, United States

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