Study of Acute Peripheral Vascular Effects, Safety and Tolerability in Subjects With Raynaud's Phenomenon Secondary to Systemic Sclerosis

NCT02228850 | Completed Phase 2

• 1 other identifier: NexMed 2014-RPS-001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

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).

Conditions

Raynaud's Phenomenon Secondary to Systemic Sclerosis

Keywords

Secondary Raynaud's Phenomenon; Secondary Raynaud's Disease; Scleroderma; Raynaud's Disease secondary to systemic sclerosis; CREST; Apricus Biosciences; laser doppler; thermography

Outcome Measures

Primary Outcomes (2)

• Pharmacodynamic evaluation: digital perfusion by laser Doppler capillary velocimetry and on digital temperature recovery with thermography.

  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.

  One month

Study Arms (3)

Alprostadil Cream (300mcg)

EXPERIMENTAL

300 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, one dispenser for each administration

Drug: Alprostadil; Other: Placebo

Alprostadil Cream (1000mcg)

EXPERIMENTAL

1000 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, one dispenser for each administration

Drug: Alprostadil; Other: Placebo

Alprostadil Cream (3000mcg)

EXPERIMENTAL

3000 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, two dispensers for each administration

Drug: Alprostadil; Other: Placebo

Interventions

Alprostadil DRUG

Alprostadil Cream (1000mcg); Alprostadil Cream (3000mcg); Alprostadil Cream (300mcg)

Placebo OTHER

Alprostadil Cream (1000mcg); Alprostadil Cream (3000mcg); Alprostadil Cream (300mcg)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Must be willing to remove nail polish and/or nail coverings from the treated hand prior to each day of study dosing;
• Must not donate blood during the study;
• Have adequate finger extension to permit application of study treatments and attachment of physiologic measuring instruments.
• Must be willing to comply with all study procedures and study visits;
• Must provide written informed consent.

You may not qualify if:

• 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;
• Tobacco smoking within six months of screening or unwillingness to avoid smoking throughout the study (e.g., cigarette, pipe, cigar, e-cigarettes) and the use of nicotine-containing products;
• Systolic Blood pressure less than 85mm/Hg;
• Prostanoid use by any route of administration within the previous six months;
• Current use of systemic or topical nitrates, endothelin receptor antagonists (e.g., bosentan) or any long-acting PDE-5 Inhibitors (e.g. tadalafil);
• Use of topical corticosteroid to the hand or fingers within 10 days of screening;

Sponsors & Collaborators

• NexMed (U.S.A.), Inc. (subsidiary of Apricus Biosciences, Inc.): lead

Study Sites (4)

Diagnamics, Inc.

Encinitas, California, 92024, United States

Location

University of Michigan Scleroderma Program - Division of Rheumatology/Dept. of Internal Medicine

Ann Arbor, Michigan, 48109, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Scleroderma Research Center - University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15261, United States

Location

MeSH Terms

Conditions

Raynaud Disease; Scleroderma, Diffuse

Interventions

Alprostadil

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins E; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Fatty Acids, Monounsaturated; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Barbara Troupin, MD, MBA

  NEXMED (U.S.A.), Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2014
• First Posted: August 29, 2014
• Study Start: November 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 22, 2016

Record last verified: 2016-03

Locations

US (4)