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

Study Overview
=================
Brief Summary
-----------------
Study CLO-311 is a multicenter, open-label, single-arm study to assess the long-term use of Clonidine Gel in the treatment of pain associated with PDN. Subjects who have completed their 12-week participation in Study CLO-290 or Study CLO-310 are eligible to rollover into this study and receive active study drug in an open-label manner.

Detailed Description
-----------------
Study CLO-311 is a multicenter, open-label, single-arm study to assess the long-term use of Clonidine Gel in the treatment of pain associated with PDN. Subjects who have completed their 12-week participation in Study CLO-290 or Study CLO-310 are eligible to rollover into this study and receive active study drug in an open-label manner. All eligible subjects will receive Clonidine Gel regardless of the blinded treatment they have received in the previous double-blind study (Clonidine Gel or Placebo Gel). Study drug will be applied topically TID to both feet for 12 months during an Open-Label Treatment Phase. Approximately 400 adult subjects with PDN are estimated to enroll in this study.

Official Title
-----------------
A Multicenter, Open-label, Single-arm Study to Evaluate the Long-term Use of Clonidine Hydrochloride Topical Gel, 0.1% in the Treatment of Pain Associated With Painful Diabetic Neuropathy

Conditions
-----------------
Painful Diabetic Neuropathy, Diabetes

Intervention / Treatment
-----------------
* Drug: clonidine hydrochloride topical gel, 0.1%


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Clonidine hydrochloride topical gel, 0.1% | Drug: clonidine hydrochloride topical gel, 0.1%<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Neuropathic Pain Symptom Inventory (NPSI) | The NPSI is a validated, self-administered questionnaire designed to evaluate the different symptoms of neuropathic pain. Each item is quantified on an 11-point (0-10) numeric scale. The NPSI includes 10 descriptors (plus 2 temporal items) that allow discrimination and quantification of 5 distinct clinically relevant dimensions of neuropathic pain syndromes. The Neuropathic Pain Symptom Inventory (NPSI) is a self-questionnaire designed to evaluate the different symptoms of neuropathic pain, which contains a list of descriptors reflecting spontaneous ongoing or paroxysmal pain, evoked pain (i.e., mechanical and thermal allodynia/hyperalgesia) and dysesthesia/paresthesia. Each of these items is quantified on an 11-point (0-10) numerical scale. NPSI total score was calculated and summarized descriptively at month 12 or the subjects last visit. The total score was calculated and summarized. | Month 12 or last visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pain, diabetic neuropathy, pain in feet