A Phase 2a Double-Blind, Randomized, Placebo-Controlled Crossover Trial of the Acute Peripheral Vascular Effects, Safety and Tolerability of Alprostadil Topical Cream in Subjects With Raynaud's Phenomenon Secondary to Systemic Sclerosis (SSc, Scleroderma)
Overview
- Phase
- Phase 2
- Intervention
- Alprostadil
- Conditions
- Raynaud's Phenomenon Secondary to Systemic Sclerosis
- Sponsor
- NexMed (U.S.A.), Inc. (subsidiary of Apricus Biosciences, Inc.)
- Enrollment
- 35
- Locations
- 4
- Primary Endpoint
- Pharmacodynamic evaluation: digital perfusion by laser Doppler capillary velocimetry and on digital temperature recovery with thermography.
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to evaluate pharmacodynamics (PD) in adult subjects with a diagnosis of Raynaud's Phenomenon secondary to Systemic Sclerosis (SSc).
Detailed Description
The purpose of this study is to evaluate the pharmacodynamic (PD) effects of topical Alprostadil on digital perfusion by laser Doppler capillary velocimetry and digital temperature recovery with thermography following standardized cold challenge and to assess the safety and tolerability of 3 doses of Alprostadil topical cream and placebo cream in adult subjects with a diagnosis of Raynaud's Phenomenon secondary to Systemic Sclerosis (SSc).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects with a diagnosis of SSc by current ACR/EULAR Classification Criteria;
- •Evidence of ongoing activity of Raynaud's Phenomenon as measured by a Raynaud Condition Score of 3 or greater at Screening;
- •All females of childbearing potential must have a negative serum pregnancy test;
- •a. Females of childbearing potential must abstain from sexual activity that could result in pregnancy, or agree to use an acceptable method of contraception throughout the study period and for 30 days following dosing of the investigational study drug. Acceptable contraception includes:
- •Intrauterine devices
- •Double barrier methods (e.g. condom or diaphragms with spermicidal gel or foam)
- •Condom use is advised for all forms of contraception
- •Must be willing and able to discontinue ongoing therapy for RP for at least 72 hours prior to each application of study medication; such drugs include calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, short-acting PDE-5i (sildenafil, vardenafil, avanafil), sympatholytics and topical or systemic nitrates;
- •Must be willing and able to discontinue consumption of caffeine-containing products (e.g., beverages and over-the-counter (OTC) medications) for at least 24 hours prior to each day of study dosing;
- •Must be willing and able to remove jewelry from the treated hand prior to each day of study dosing;
Exclusion Criteria
- •BMI less than 18.5;
- •Clinically significant medical abnormality or history or presence of significant neurological, hepatic, renal, endocrine, gastrointestinal, cardiovascular, pulmonary, psychiatric and/or metabolic condition as determined by the Investigator);
- •Clinical diagnosis of Systemic Sclerosis in association with other rheumatologic diseases including Mixed Connective Tissue Disease;
- •Clinically significant abnormal laboratory test results at screening as determined by the Investigator;
- •Raynaud's Phenomenon thought to be of non-systemic sclerosis etiology;
- •Peripheral or central vasculopathy other than Systemic Sclerosis;
- •History of Scleroderma renal crisis or currently being treated for hypertension, however, subjects with controlled hypertension will not be excluded;
- •Active digital ulcers or rash on hand intended for study medication;
- •History in the past (5) five years of autonomic neuropathy or postural hypotension;
- •Upper extremity sympathectomy at any level in the 12 months prior to study;
Arms & Interventions
Alprostadil Cream (300mcg)
300 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, one dispenser for each administration
Intervention: Alprostadil
Alprostadil Cream (300mcg)
300 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, one dispenser for each administration
Intervention: Placebo
Alprostadil Cream (1000mcg)
1000 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, one dispenser for each administration
Intervention: Alprostadil
Alprostadil Cream (1000mcg)
1000 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, one dispenser for each administration
Intervention: Placebo
Alprostadil Cream (3000mcg)
3000 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, two dispensers for each administration
Intervention: Alprostadil
Alprostadil Cream (3000mcg)
3000 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, two dispensers for each administration
Intervention: Placebo
Outcomes
Primary Outcomes
Pharmacodynamic evaluation: digital perfusion by laser Doppler capillary velocimetry and on digital temperature recovery with thermography.
Time Frame: two hours (intermittently) after cold-challenge and post-dose
Safety assessments based on review of adverse events, vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests.
Time Frame: One month