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

Inclusion Criteria

• 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.

Exclusion Criteria

• 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