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

Primary Purpose

Painful Diabetic Neuropathy

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo Gel
Clonidine Topical Gel (ARC-4558)
Sponsored by
Arcion Therapeutics Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Painful Diabetic Neuropathy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham, School of Medicine
  • Northern California Research
  • Neurological Research Institute
  • Metabolic Research Institute
  • Pain Treatment Center of the Bluegrass
  • Tulane University Health Sciences Center
  • University of Massachuetts Medical School, Division of Diabetes- Clinical Research Office
  • The Creighton Diabetes Center
  • University of Rochester Medical Center
  • The Center for Clinical Research
  • Cleveland Clinic
  • Waccamaw Pain Partners/Crescent Moon Research
  • The Nerve and Muscle Center of Texas
  • Diabetes and Glandular Disease Center
  • Strelitz Diabetes Institute, Eastern Virginia Medical School
  • Swedish Pain Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo Gel

Clonidine Topical Gel (ARC-4558)

Arm Description

Placebo Gel is vehicle without clonidine

Clonidine Topical Gel contains 0.1% clonidine hydrochloride

Outcomes

Primary Outcome Measures

Change From Baseline to Week 12 in the Average Daily Pain NPRS (Numeric Pain Rating Scale) Score; mLOCF Imputation
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
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
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
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
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
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
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)
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)
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)
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
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
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
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
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.

Full Information

First Posted
June 10, 2008
Last Updated
September 21, 2016
Sponsor
Arcion Therapeutics Inc
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1. Study Identification

Unique Protocol Identification Number
NCT00695565
Brief Title
Efficacy and Safety Study of ARC-4558 for Management of Pain Associated With Painful Diabetic Neuropathy
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arcion Therapeutics Inc

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Painful Diabetic Neuropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
180 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo Gel
Arm Type
Placebo Comparator
Arm Description
Placebo Gel is vehicle without clonidine
Arm Title
Clonidine Topical Gel (ARC-4558)
Arm Type
Active Comparator
Arm Description
Clonidine Topical Gel contains 0.1% clonidine hydrochloride
Intervention Type
Drug
Intervention Name(s)
Placebo Gel
Intervention Description
TID x 12 weeks
Intervention Type
Drug
Intervention Name(s)
Clonidine Topical Gel (ARC-4558)
Intervention Description
TID x 12 weeks
Primary Outcome Measure Information:
Title
Change From Baseline to Week 12 in the Average Daily Pain NPRS (Numeric Pain Rating Scale) Score; mLOCF Imputation
Description
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).
Time Frame
Baseline (average of Days -7 to -1) and Week 12 (Average of Days 78 to 84)
Secondary Outcome Measure Information:
Title
Change From Baseline in Average Daily Pain NPRS Score for Each Week of Treatment; mLOCF Imputation
Description
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).
Time Frame
Baseline (average of Days -7 to -1) and Weeks 1 through 12 (weekly averages)
Title
Change From Baseline to Week 12 in the Worst Daily Pain NPRS Score; mLOCF Imputation
Description
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).
Time Frame
Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Title
Percentage of Subjects Who Experience at Least 30% Reduction in Average Daily Pain From Baseline; mLOCF Imputation
Description
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".
Time Frame
Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Title
Percentage of Subjects Who Experience at Least 50% Reduction in Average Daily Pain From Baseline; mLOCF Imputation
Description
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".
Time Frame
Baseline (average of Days -7 to -1) and Week 12 (average of Days 78 to 84)
Title
Change From Baseline in the Brief Pain Inventory (BPI) Severity Scale at Week 12; mLOCF Imputation
Description
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).
Time Frame
Baseline and Week 12
Title
Change From Baseline in the Brief Pain Inventory Functional Interference Scale at Week 12; mLOCF Imputation
Description
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.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in Overall Quality of Sleep (Chronic Pain Sleep Inventory)
Description
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.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in the Depression Score of the Hospital Anxiety and Depression Scale (HADS)
Description
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.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in the Anxiety Score of the Hospital Anxiety and Depression Scale (HADS)
Description
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.
Time Frame
Baseline and Week 12
Title
Change From Baseline to Week 12 in the McGill Pain Questionnaire (Short Form) Total Score
Description
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).
Time Frame
Baseline and Week 12
Title
Patient Global Impression of Change (PGIC) at Week 12
Description
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.
Time Frame
Week 12
Title
Clinician Global Impression of Change (CGIC) at Week 12
Description
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.
Time Frame
Week 12
Title
Change in Blood Pressure From Baseline to Week 12
Description
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.
Time Frame
Baseline and Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James N Campbell, M.D.
Organizational Affiliation
Arcion Therapeutics Inc
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham, School of Medicine
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Northern California Research
City
Sacramento
State/Province
California
ZIP/Postal Code
95821
Country
United States
Facility Name
Neurological Research Institute
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Metabolic Research Institute
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
Pain Treatment Center of the Bluegrass
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University of Massachuetts Medical School, Division of Diabetes- Clinical Research Office
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
The Creighton Diabetes Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
The Center for Clinical Research
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Waccamaw Pain Partners/Crescent Moon Research
City
Murrells Inlet
State/Province
South Carolina
ZIP/Postal Code
29576
Country
United States
Facility Name
The Nerve and Muscle Center of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Diabetes and Glandular Disease Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Strelitz Diabetes Institute, Eastern Virginia Medical School
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Facility Name
Swedish Pain Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
22683276
Citation
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.
Results Reference
result
PubMed Identifier
35587172
Citation
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.
Results Reference
derived

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

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