Study of Clonidine Hydrochloride Topical Gel, 0.1% in the Treatment of Pain Associated With Diabetic Neuropathy

NCT02068027 | Completed Phase 2 Results

• 1 other identifier: CLO-290
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 23

Brief Summary

The purpose of the study is to determine whether clonidine gel is an effective treatment for reducing the pain associated with painful diabetic neuropathy.

Conditions

Painful Diabetic Neuropathy; Diabetic Neuropathy; Neuropathy

Keywords

Diabetes Mellitus; Pain; Foot pain; Neuropathy

Outcome Measures

Primary Outcomes (1)

• 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.

  The change from Baseline (averaged over Day -14 to Day -8) to End-of-Treatment (averaged over Days 78 to 84 [±3 days])

Secondary Outcomes (1)

• 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])

Study Arms (2)

Clonidine Gel 0.1%

EXPERIMENTAL

Clonidine hydrochloride topical gel, 0.1%

Drug: Clonidine Gel 0.1%

Placebo

PLACEBO COMPARATOR

Placebo gel of identical appearance as active treatment

Drug: Placebo

Interventions

Clonidine Gel 0.1% DRUG

Clonidine Gel 0.1%

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has provided written informed consent.
• The subject is an outpatient aged 18 to 85 years (inclusive) at the time of the Screening Visit.
• The subject has Type 1 or Type 2 diabetes mellitus with glycemic control that has been optimized and has been stable on diet therapy, oral anti-hyperglycemic agents and/or insulin, for at least three (3) months prior to the Screening Visit.
• The subject must be 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). Non-pregnancy will be confirmed (as applicable) by a pregnancy test conducted at the Screening and Randomization Visits. Double-barrier methods, hormonal contraceptives, and abstinence are acceptable birth control methods for this study.
• The subject has chronic pain attributable to a symmetrical stocking distribution neuropathy in the lower extremities for at least three (3) months. A loss of distal sensation and/or tingling paresthesia primarily in the toes and fingers is acceptable, but must be of secondary importance to the distal neuropathic pain. Pain should be clearly localized to the area of neuropathy (feet) and subjects should be able to distinguish this pain (the target pain) from other painful areas and conditions.
• The subject has an average pain score relevant to the target pain in the feet of ≥4 on an 11-point Numeric Pain Rating Scale over the previous 24 hours at Screening.
• The subject has a pain score of at least 2, on the 11-point Numeric Pain Rating Scale , within 30 minutes following topical 0.1% capsaicin application with occlusive dressing to the pretibial area.
• The subject has a mean daily average pain score relevant to the target pain in the feet of ≥4 on an 11-point Numeric Pain Rating Scale during the Baseline Phase.
• The subject has met the pain evaluation and scoring criteria at the end of the Placebo Lead-in Phase by having a mean daily average pain score relevant to the target pain in the feet of ≥4 on an 11-point Numeric Pain Rating Scale without having a decrease in their pain score greater than 20% compared to the Baseline Phase score in the 11-point Numeric Pain Rating Scale .
• The 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, ECG, and laboratory evaluation.
• If taking chronic oral pain medications, the subject must be on a stable regimen for at least 14 days prior to the Baseline Visit with the expectation that the medications, dose(s) and schedule will remain stable throughout the study. For medications containing non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, subjects must be on a stable dose for at least 7 days prior to the Baseline Visit. As needed pain medications will be limited to acetaminophen from Day -8 until the end of the treatment period. Low dose aspirin (81 mg/day) is not considered as analgesic therapy.
• Subject is compliant with daily pain assessments during the Baseline Phase and Placebo Lead in Phase of the study by recording their Numeric Pain Rating Scale score at least 5 days and the last 3 days of the previous 7 days.
• Subject is alert and has the capabilities of applying topical gel to both feet three times daily. A caregiver, trained by the study staff to apply study drug, would be a suitable alternative to self-application of the treatment.

You may not qualify if:

• The subject has neuropathy secondary to non-diabetic causes in the opinion of the Investigator (e.g., significant vasculitis, collagen vascular disorder, familial neuropathy, alcoholism, pernicious anemia, hepatitis, malignancy, syphilis, post-herpetic neuralgia, chronic inflammatory demyelinating polyradiculopathy, human immunodeficiency virus \[HIV\], medication-induced neuropathy, vitamin B12 deficiency).
• The subject has a significant neurological disorder or a condition that can cause symptoms that mimic peripheral neuropathy or might confound assessment of painful diabetic neuropathy (e.g., stroke with distal neurological deficit, mononeuritis multiplex, lumbar radiculopathy, multiple sclerosis) or has significant asymmetric neuropathic signs and symptoms.
• The subject has other sustained pain with intensity at or greater than the bilateral neuropathic pain in the feet/toes.
• The subject is using an implanted medical device (e.g., spinal cord stimulator, intrathecal pump, or peripheral nerve stimulator) for the treatment of pain.
• The subject has no pin-prick sensitivity to Neuropen testing of non-calloused areas of the foot.
• The subject is clinically hypotensive with a resting diastolic blood pressure \<60 mm Hg or a systolic blood pressure \<90 mm Hg.
• The subject has recent history (within the past 3 months) or current symptoms of orthostatic hypotension with a sudden fall in blood pressure on standing accompanied by dizziness and lightheadedness.
• The subject has a history of foot or toe amputation, or an active foot or toe ulcer.
• The 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.
• The subject has a history of substance abuse disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) within the past year, has current evidence for substance abuse disorder, is receiving medicinal treatment for drug abuse, or tests positive upon urine drug screen for a non-prescribed substance of abuse.
• The subject has used capsaicin on the feet for greater than 2 consecutive weeks in the previous 3 months.
• The 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) requiring oxygen therapy.
• The subject has a serum creatinine value \>2.0 mg/dL or a value for alanine transaminase (ALT) or aspartate transaminase (AST) \>2.5 times the upper limit of normal at Screening.
• The subject was dosed with an investigational drug within 30 days prior to the Screening Visit.
• The subject is likely to be noncompliant or unreliable in providing pain ratings as judged by the Investigator.

Sponsors & Collaborators

• BioDelivery Sciences International: lead

Study Sites (23)

Unknown Facility

Phoenix, Arizona, 85023, United States

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Santa Monica, California, 90404, United States

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Walnut Creek, California, 94598, United States

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Milford, Connecticut, 06460, United States

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Waterbury, Connecticut, 06708, United States

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Bradenton, Florida, 34205, United States

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Brandon, Florida, 33511, United States

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Jupiter, Florida, 33458, United States

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Miami, Florida, 33143, United States

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Tampa, Florida, 33606, United States

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West Palm Beach, Florida, 33401, United States

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Columbus, Georgia, 31904, United States

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Evansville, Indiana, 47714, United States

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Kansas City, Kansas, 66160, United States

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Hazelwood, Missouri, 63042, United States

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Winston-Salem, North Carolina, 27103, United States

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Warwick, Rhode Island, 02886, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Dallas, Texas, 75230, United States

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Houston, Texas, 77055, United States

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San Antonio, Texas, 78229, United States

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Virginia Beach, Virginia, 23451, United States

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Renton, Washington, 98057, United States

Location

Related Publications (1)

• 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.

  PMID: 35587172 DERIVED

MeSH Terms

Conditions

Diabetic Neuropathies; Diabetes Mellitus; Pain

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Vice President Clinical Operations
• Organization: BDSI

twarneke@bdsi.com

919-582-0294

Study Officials

• Aziz Shaibani, MD

  Nerve & Muscle Center of Texas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2014
• First Posted: February 20, 2014
• Study Start: March 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: September 26, 2017
• Results First Posted: August 24, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)