The Efficacy and Safety of Clonidine Hydrochloride Topical Gel, vs Clonidine Hydrochloride Gel Comparator to Treat Painful Diabetic Neuropathy
Primary Purpose
Painful Diabetic Neuropathy, Diabetic Neuropathy, Neuropathy
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Clonidine Hydrochloride Topical Gel, 0.1%
Clonidine Hydrochloride Gel Comparator
Sponsored by
About this trial
This is an interventional treatment trial for Painful Diabetic Neuropathy focused on measuring Diabetes Mellitus, Pain, Foot Pain, Neuropathy
Eligibility Criteria
Inclusion Criteria:
- Subject is fluent in English and has provided written informed consent.
- Subject is an outpatient ≥18 years of age at the time of the Screening Visit.
- Subject has Type 1 or Type 2 diabetes mellitus with a hemoglobin A1C value < 10% and has been stable on therapy (diet, oral anti-hyperglycemic, and/or insulin) for at least six (6) months prior to the Screening Visit.
- Subject is a male or non-pregnant, non-lactating female. Females must be practicing an acceptable method of birth control or be surgically sterile or postmenopausal (amenorrhea for ≥12 months). A negative pregnancy test at the Screening and Day 1 visits is required for females of child-bearing potential. Double-barrier methods, hormonal contraceptives, and abstinence are acceptable birth control methods for this study.
- Subject has chronic pain attributable to a symmetrical stocking distribution neuropathy in the lower extremities for at least six (6) months. Pain should be clearly localized to the area of neuropathy (feet), and subjects should be able to distinguish the target pain from other painful areas and conditions.
- Subject has an average pain score relevant to the target pain in the feet of ≥4 on an 11 point numerical pain rating scale over the previous 24 hours at the Screening Visit.
- Subject meets a pre-specified, minimum numerical pain rating scale score following capsaicin skin challenge.
- Subject must satisfactorily complete Accurate Pain Reporting and Minimizing Placebo Response Training.
- Subject must have moderate to severe pain during the Screening Run-in Phase.
- Subjects must be 75 to 110% compliant with application of study drug during the Screening Run-in Phase
- Subject has been medically stable for at least 30 days prior to the Screening Visit, and in the opinion of the Investigator, is in otherwise good general health based on medical history, physical examination, electrocardiogram, and laboratory evaluation.
Exclusion Criteria:
- Subject has neuropathy secondary to non-diabetic causes in the opinion of the Investigator (e.g., vasculitis, familial neuropathy, alcoholism, pernicious anemia, hepatitis, malignancy, chronic inflammatory demyelinating polyneuropathy [CIDP], human immunodeficiency virus [HIV], medication-induced neuropathy, vitamin B12 deficiency).
- Subject has a significant neurological disorder or condition that might confound assessment of painful diabetic neuropathy (e.g., stroke with distal neurological deficit, mononeuritis multiplex, lumbar radiculopathy).
- Subject has a confounding disorder as determined by the Algorithm for Excluding Disorders that Masquerade as Painful Diabetic Neuropathy.
- Subject has other sustained pain with intensity at or greater than the bilateral neuropathic pain in the feet.
- Subject is using an implanted medical device (e.g., spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for treatment of pain.
- Subject is hypotensive with a resting diastolic blood pressure <60 mm Hg or a systolic blood pressure <90 mm Hg at the Screening or Day 1 Visit.
- The subject has recent history (within the past 3 months) or current symptoms of orthostatic hypotension.
- Subject has a history of foot or toe amputation or an active foot or toe ulcer.
- Subject has any significant or unstable medical or psychiatric condition that, in the opinion of the Investigator, would interfere with his/her ability to participate in the study.
- Subject has a history of substance abuse disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, within the past year, has current evidence of substance abuse disorder, is receiving medical treatment for drug abuse, or has a positive urine drug screen for a non-prescribed substance of abuse.
- Subject is receiving or has received within 30 days prior to the Screening Visit any prohibited medications or is anticipated to receive after the start of the trial any new prescription medication for their painful diabetic neuropathy. Subjects may be enrolled if stable on therapy for painful diabetic neuropathy.
- Subject has symptomatic or severe coronary insufficiency, clinically significant cardiac conduction disturbances, myocardial infarction (within last 12 months), moderate to severe cerebrovascular disease, or severe chronic obstructive pulmonary disease (COPD).
- Subject has estimated creatinine clearance less than 50 mL/min (Cockcroft Gault) at the Screening Visit.
- Subject has serum alanine transaminase (ALT) or aspartate transaminase (AST) >3.0 times the upper limit of normal or total bilirubin concentrations >2.0 times the upper limit of normal at the Screening Visit.
- Subject has received an investigational drug within 30 days prior to the Screening Visit.
- Subject has been treated previously with clonidine topical gel or participated in a clonidine topical gel clinical study, including Study CLO 290.
- Subject is currently taking or has taken clonidine (any formulation) over the past 4 weeks.
- Subject has known hypersensitivity or intolerance to clonidine.
- Subject is receiving or has received ≤7 days prior to the start of the Screening Phase "alternative medicine" products or treatments (e.g., acupuncture, naturopathy, homeopathy, etc.) for management of pain.
- Subject has a history of malignancy within the past 5 years except for successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin and/or localized carcinoma in situ of the cervix.
- Subject is planning to have surgery during the course of the study.
- Subject has significant skin changes on physical examination associated with either pedal edema or venous stasis disease.
- Subject has any dermatologic condition of the lower extremities that could affect study drug absorption
- Subject has current symptoms of depression with a Beck Depression Inventory II (BDI II) score >19 at the Screening Visit.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Clonidine Hydrochloride Topical Gel,0.1%
Clonidine Hydrochloride Gel Comparator
Arm Description
Clonidine Hydrochloride Topical Gel,0.1%
Clonidine Hydrochloride Gel Comparator
Outcomes
Primary Outcome Measures
Change From Baseline to Day 84 (Week 12) in Numeric Pain Rating Scale Score
The Numeric Pain Rating Scale is a single reading that measures the patients interpretation of their pain on a scale from 0, no pain to 10, worst pain imaginable. The change from baseline can range from -10 to 10. The change from Baseline (averaged over Day -14 to Day -8) to End-of-Treatment (averaged over Days 78 to 84 [±3 days]) in the Numeric Pain Rating Scale score assessing the "average pain in the past 24 hours in the painful areas of the feet" averaged over Days 78 to 84 compared to the 7 days at the Baseline Phase (Days -14 to -8). For the primary efficacy endpoint, the mean change in pain intensity from Baseline to Week 12 was analyzed using an analysis of covariance (ANCOVA) model with the Baseline pain intensity score serving as a covariate. The statistical model also included treatment, site, site by treatment interaction, and strata. If the site by treatment interaction term was not significant at the 0.1 level, then it was excluded from the model.
Secondary Outcome Measures
Mean Daily Worst Pain Intensity Numeric Pain Rating Scale Scores
The Numeric Pain Rating Scale is a single reading that measures the patients interpretation of their pain on a scale from 0, no pain to 10, worst pain imaginable. The change from baseline can range from -10 to 10. The change from Baseline (worse score from Day -14 to Day -8) to End-of-Treatment (worse score during Days 78 to 84 [±3 days]) in the Numeric Pain Rating Scale score assessing the "worse pain in the past 24 hours in the painful areas of the feet" from Days 78 to 84 compared to the 7 days at the Baseline Phase (Days -14 to -8). For the primary efficacy endpoint, the mean change in pain intensity from Baseline to Week 12 was analyzed using an analysis of covariance (ANCOVA) model with the Baseline pain intensity score serving as a covariate. The statistical model also included treatment, site, site by treatment interaction, and strata. If the site by treatment interaction term was not significant at the 0.1 level, then it was excluded from the model.
Full Information
NCT ID
NCT02643251
First Posted
December 29, 2015
Last Updated
August 23, 2017
Sponsor
BioDelivery Sciences International
1. Study Identification
Unique Protocol Identification Number
NCT02643251
Brief Title
The Efficacy and Safety of Clonidine Hydrochloride Topical Gel, vs Clonidine Hydrochloride Gel Comparator to Treat Painful Diabetic Neuropathy
Official Title
A Multicenter, Randomized, Double Blind, Parallel-Group Study Comparing the Efficacy and Safety of Clonidine Hydrochloride Topical Gel, 0.1%, to Clonidine Hydrochloride Gel Comparator in the Management of Painful Diabetic Neuropathy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
December 2015 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioDelivery Sciences International
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study will include three (3) phases: Screening Phase, Treatment Phase, and Follow-up Phase. Subjects who qualify to participate will apply study drug to their feet three times daily and will record their daily pain scores using an interactive voice response system (IVRS) during the Treatment Phase for 12 weeks. Approximately 100 adult subjects will be randomized to receive Clonidine Gel or Clonidine Gel Comparator.
Detailed Description
Study CLO-291 is a randomized, double-blind, comparator-controlled, parallel-group, multicenter study of 0.1% clonidine topical gel (Clonidine Gel) for the treatment of pain associated with painful diabetic neuropathy. The study will include three (3) phases: Screening Phase, Treatment Phase, and Follow-up Phase. Subjects who satisfy all eligibility criteria will apply Clonidine Gel Comparator to their feet three times daily and will record their daily pain scores using an interactive voice response system (IVRS). Approximately 100 adult subjects will be randomized to receive Clonidine Gel or Clonidine Gel Comparator during the 12 week Treatment Phase.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Painful Diabetic Neuropathy, Diabetic Neuropathy, Neuropathy
Keywords
Diabetes Mellitus, Pain, Foot Pain, Neuropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
138 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Clonidine Hydrochloride Topical Gel,0.1%
Arm Type
Experimental
Arm Description
Clonidine Hydrochloride Topical Gel,0.1%
Arm Title
Clonidine Hydrochloride Gel Comparator
Arm Type
Placebo Comparator
Arm Description
Clonidine Hydrochloride Gel Comparator
Intervention Type
Drug
Intervention Name(s)
Clonidine Hydrochloride Topical Gel, 0.1%
Other Intervention Name(s)
Clonidine Gel
Intervention Description
Clonidine Gel is supplied as an aqueous gel formulation for topical use.
Intervention Type
Drug
Intervention Name(s)
Clonidine Hydrochloride Gel Comparator
Other Intervention Name(s)
Clonidine Gel Comparator
Intervention Description
Clonidine Gel Comparator is supplied as an aqueous gel formulation for topical use.
Primary Outcome Measure Information:
Title
Change From Baseline to Day 84 (Week 12) in Numeric Pain Rating Scale Score
Description
The Numeric Pain Rating Scale is a single reading that measures the patients interpretation of their pain on a scale from 0, no pain to 10, worst pain imaginable. The change from baseline can range from -10 to 10. The change from Baseline (averaged over Day -14 to Day -8) to End-of-Treatment (averaged over Days 78 to 84 [±3 days]) in the Numeric Pain Rating Scale score assessing the "average pain in the past 24 hours in the painful areas of the feet" averaged over Days 78 to 84 compared to the 7 days at the Baseline Phase (Days -14 to -8). For the primary efficacy endpoint, the mean change in pain intensity from Baseline to Week 12 was analyzed using an analysis of covariance (ANCOVA) model with the Baseline pain intensity score serving as a covariate. The statistical model also included treatment, site, site by treatment interaction, and strata. If the site by treatment interaction term was not significant at the 0.1 level, then it was excluded from the model.
Time Frame
The change from Baseline (averaged over Day -14 to Day -8) to End-of-Treatment (averaged over Days 78 to 84 [±3 days])
Secondary Outcome Measure Information:
Title
Mean Daily Worst Pain Intensity Numeric Pain Rating Scale Scores
Description
The Numeric Pain Rating Scale is a single reading that measures the patients interpretation of their pain on a scale from 0, no pain to 10, worst pain imaginable. The change from baseline can range from -10 to 10. The change from Baseline (worse score from Day -14 to Day -8) to End-of-Treatment (worse score during Days 78 to 84 [±3 days]) in the Numeric Pain Rating Scale score assessing the "worse pain in the past 24 hours in the painful areas of the feet" from Days 78 to 84 compared to the 7 days at the Baseline Phase (Days -14 to -8). For the primary efficacy endpoint, the mean change in pain intensity from Baseline to Week 12 was analyzed using an analysis of covariance (ANCOVA) model with the Baseline pain intensity score serving as a covariate. The statistical model also included treatment, site, site by treatment interaction, and strata. If the site by treatment interaction term was not significant at the 0.1 level, then it was excluded from the model.
Time Frame
The change from Baseline (worse over Day -14 to Day -8) to End-of-Treatment (worse over Days 78 to 84 [±3 days])
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject is fluent in English and has provided written informed consent.
Subject is an outpatient ≥18 years of age at the time of the Screening Visit.
Subject has Type 1 or Type 2 diabetes mellitus with a hemoglobin A1C value < 10% and has been stable on therapy (diet, oral anti-hyperglycemic, and/or insulin) for at least six (6) months prior to the Screening Visit.
Subject is a male or non-pregnant, non-lactating female. Females must be practicing an acceptable method of birth control or be surgically sterile or postmenopausal (amenorrhea for ≥12 months). A negative pregnancy test at the Screening and Day 1 visits is required for females of child-bearing potential. Double-barrier methods, hormonal contraceptives, and abstinence are acceptable birth control methods for this study.
Subject has chronic pain attributable to a symmetrical stocking distribution neuropathy in the lower extremities for at least six (6) months. Pain should be clearly localized to the area of neuropathy (feet), and subjects should be able to distinguish the target pain from other painful areas and conditions.
Subject has an average pain score relevant to the target pain in the feet of ≥4 on an 11 point numerical pain rating scale over the previous 24 hours at the Screening Visit.
Subject meets a pre-specified, minimum numerical pain rating scale score following capsaicin skin challenge.
Subject must satisfactorily complete Accurate Pain Reporting and Minimizing Placebo Response Training.
Subject must have moderate to severe pain during the Screening Run-in Phase.
Subjects must be 75 to 110% compliant with application of study drug during the Screening Run-in Phase
Subject has been medically stable for at least 30 days prior to the Screening Visit, and in the opinion of the Investigator, is in otherwise good general health based on medical history, physical examination, electrocardiogram, and laboratory evaluation.
Exclusion Criteria:
Subject has neuropathy secondary to non-diabetic causes in the opinion of the Investigator (e.g., vasculitis, familial neuropathy, alcoholism, pernicious anemia, hepatitis, malignancy, chronic inflammatory demyelinating polyneuropathy [CIDP], human immunodeficiency virus [HIV], medication-induced neuropathy, vitamin B12 deficiency).
Subject has a significant neurological disorder or condition that might confound assessment of painful diabetic neuropathy (e.g., stroke with distal neurological deficit, mononeuritis multiplex, lumbar radiculopathy).
Subject has a confounding disorder as determined by the Algorithm for Excluding Disorders that Masquerade as Painful Diabetic Neuropathy.
Subject has other sustained pain with intensity at or greater than the bilateral neuropathic pain in the feet.
Subject is using an implanted medical device (e.g., spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for treatment of pain.
Subject is hypotensive with a resting diastolic blood pressure <60 mm Hg or a systolic blood pressure <90 mm Hg at the Screening or Day 1 Visit.
The subject has recent history (within the past 3 months) or current symptoms of orthostatic hypotension.
Subject has a history of foot or toe amputation or an active foot or toe ulcer.
Subject has any significant or unstable medical or psychiatric condition that, in the opinion of the Investigator, would interfere with his/her ability to participate in the study.
Subject has a history of substance abuse disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, within the past year, has current evidence of substance abuse disorder, is receiving medical treatment for drug abuse, or has a positive urine drug screen for a non-prescribed substance of abuse.
Subject is receiving or has received within 30 days prior to the Screening Visit any prohibited medications or is anticipated to receive after the start of the trial any new prescription medication for their painful diabetic neuropathy. Subjects may be enrolled if stable on therapy for painful diabetic neuropathy.
Subject has symptomatic or severe coronary insufficiency, clinically significant cardiac conduction disturbances, myocardial infarction (within last 12 months), moderate to severe cerebrovascular disease, or severe chronic obstructive pulmonary disease (COPD).
Subject has estimated creatinine clearance less than 50 mL/min (Cockcroft Gault) at the Screening Visit.
Subject has serum alanine transaminase (ALT) or aspartate transaminase (AST) >3.0 times the upper limit of normal or total bilirubin concentrations >2.0 times the upper limit of normal at the Screening Visit.
Subject has received an investigational drug within 30 days prior to the Screening Visit.
Subject has been treated previously with clonidine topical gel or participated in a clonidine topical gel clinical study, including Study CLO 290.
Subject is currently taking or has taken clonidine (any formulation) over the past 4 weeks.
Subject has known hypersensitivity or intolerance to clonidine.
Subject is receiving or has received ≤7 days prior to the start of the Screening Phase "alternative medicine" products or treatments (e.g., acupuncture, naturopathy, homeopathy, etc.) for management of pain.
Subject has a history of malignancy within the past 5 years except for successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin and/or localized carcinoma in situ of the cervix.
Subject is planning to have surgery during the course of the study.
Subject has significant skin changes on physical examination associated with either pedal edema or venous stasis disease.
Subject has any dermatologic condition of the lower extremities that could affect study drug absorption
Subject has current symptoms of depression with a Beck Depression Inventory II (BDI II) score >19 at the Screening Visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aziz Shaibani, MD
Organizational Affiliation
Nerve and Muscule Center of Texas
Official's Role
Principal Investigator
Facility Information:
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85308
Country
United States
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85023
Country
United States
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
City
Norco
State/Province
California
ZIP/Postal Code
92860
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95821
Country
United States
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33912
Country
United States
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32801
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33634
Country
United States
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
City
Blackfoot
State/Province
Idaho
ZIP/Postal Code
83321
Country
United States
City
Boise
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
City
Belleville
State/Province
Illinois
ZIP/Postal Code
62220
Country
United States
City
Blue Island
State/Province
Illinois
ZIP/Postal Code
60406
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60616
Country
United States
City
Hazelwood
State/Province
Missouri
ZIP/Postal Code
63042
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78218
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78228
Country
United States
12. IPD Sharing Statement
Learn more about this trial
The Efficacy and Safety of Clonidine Hydrochloride Topical Gel, vs Clonidine Hydrochloride Gel Comparator to Treat Painful Diabetic Neuropathy
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