A Safety Study of Clonidine Hydrochloride Topical Gel, 0.1% in the Treatment of Painful Diabetic Neuropathy

Inclusion Criteria

• The subject has provided written informed consent.
• The subject has Type 1 or Type 2 diabetes mellitus with glycemic control that has been optimized on diet therapy, oral anti-hyperglycemic agents and/or insulin.
• 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 Entry Visit. Double-barrier methods, hormonal contraceptives, and abstinence are acceptable birth control methods for this study.
• The subject has completed their 12-week participation according to the protocol in the previously conducted double-blind study, CLO-290.
• The subject is medically stable at the end-of-study visit (Day 85) of Study CLO-290, and in the opinion of the Investigator, is in otherwise good general health based on physical examination, ECG, and laboratory evaluation.
• Subject has the capabilities of applying topical gel to both feet TID. A caregiver, trained by the study staff to apply study medication, would be a suitable alternative to self-application of the treatment.

Exclusion Criteria

• 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 is clinically hypotensive with a resting diastolic blood pressure <60 mmHg or a systolic blood pressure <90 mmHg.
• 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 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 DSM-IV-TR within the past 6 months, has current evidence for substance abuse disorder, or is receiving medicinal treatment for drug abuse.
• The subject has symptomatic or severe coronary insufficiency, clinically significant cardiac conduction disturbances, myocardial infarction (within last 6 months), cerebrovascular disease, or chronic obstructive pulmonary disease (COPD) requiring oxygen therapy.
• The subject is likely to be noncompliant or unreliable in providing ratings as judged by the Investigator.
• The subject has evidence of clinically significant peripheral vascular disease as evidenced by a history of intermittent claudication or evidence of vascular ulcers, including venous stasis ulcers.
• The subject is currently taking or has taken clonidine in any form other than Clonidine Gel study drug (i.e., oral, transdermal patch) over the past 4 months.
• The subject has developed hypersensitivity or intolerance to clonidine.
• The subject is currently receiving any non-oral treatment that could affect neuropathic pain.
• Subject has a history of malignancy within the past 5 years with the exception of successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin and/or localized carcinoma in situ of the cervix.
• The subject has clinical evidence of pedal edema or venous stasis disease associated with significant skin changes on physical examination.