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
Overview
- Phase
- Phase 2
- Intervention
- Clonidine Hydrochloride Topical Gel, 0.1%
- Conditions
- Painful Diabetic Neuropathy
- Sponsor
- BioDelivery Sciences International
- Enrollment
- 138
- Primary Endpoint
- Change From Baseline to Day 84 (Week 12) in Numeric Pain Rating Scale Score
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
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
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.
Arms & Interventions
Clonidine Hydrochloride Topical Gel,0.1%
Clonidine Hydrochloride Topical Gel,0.1%
Intervention: Clonidine Hydrochloride Topical Gel, 0.1%
Clonidine Hydrochloride Gel Comparator
Clonidine Hydrochloride Gel Comparator
Intervention: Clonidine Hydrochloride Gel Comparator
Outcomes
Primary Outcomes
Change From Baseline to Day 84 (Week 12) in Numeric Pain Rating Scale Score
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])
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 Outcomes
- Mean Daily Worst Pain Intensity Numeric Pain Rating Scale Scores(The change from Baseline (worse over Day -14 to Day -8) to End-of-Treatment (worse over Days 78 to 84 [±3 days]))