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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Arcion Therapeutics Inc
ClinicalTrials.gov Identifier:
NCT00695565
First received: June 10, 2008
Last updated: September 21, 2016
Last verified: September 2016
  Purpose
The purpose of this study is to determine whether ARC-4558 is effective in managing pain associated with painful diabetic neuropathy.

Condition Intervention Phase
Painful Diabetic Neuropathy
Drug: Placebo Gel
Drug: Clonidine Topical Gel (ARC-4558)
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Arcion Therapeutics Inc:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    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:
  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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".

  • 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) ] [ Designated as safety issue: No ]
    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 in the Brief Pain Inventory (BPI) Severity Scale at Week 12; mLOCF Imputation [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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 in the Brief Pain Inventory Functional Interference Scale at Week 12; mLOCF Imputation [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline to Week 12 in Overall Quality of Sleep (Chronic Pain Sleep Inventory) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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 Depression Score of the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 12 in the Anxiety Score of the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 12 in the McGill Pain Questionnaire (Short Form) Total Score [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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).

  • Patient Global Impression of Change (PGIC) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • Clinician Global Impression of Change (CGIC) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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 in Blood Pressure From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 180
Study Start Date: May 2008
Study Completion Date: February 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Gel
Placebo Gel is vehicle without clonidine
Drug: Placebo Gel
TID x 12 weeks
Active Comparator: Clonidine Topical Gel (ARC-4558)
Clonidine Topical Gel contains 0.1% clonidine hydrochloride
Drug: Clonidine Topical Gel (ARC-4558)
TID x 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00695565

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

Publications:
Responsible Party: Arcion Therapeutics Inc
ClinicalTrials.gov Identifier: NCT00695565     History of Changes
Other Study ID Numbers: CLO-027 
Study First Received: June 10, 2008
Results First Received: July 11, 2013
Last Updated: September 21, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Pain
Diabetic Neuropathies
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Peripheral Nervous System Diseases
Neuromuscular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Clonidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 08, 2016