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

Primary Purpose

Raynaud's Phenomenon Secondary to Systemic Sclerosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Alprostadil
Placebo
Sponsored by
NexMed (U.S.A.), Inc. (subsidiary of Apricus Biosciences, Inc.)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Raynaud's Phenomenon Secondary to Systemic Sclerosis focused on measuring Secondary Raynaud's Phenomenon, Secondary Raynaud's Disease, Scleroderma, Raynaud's Disease secondary to systemic sclerosis, CREST, Apricus Biosciences, laser doppler, thermography

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

    1. Intrauterine devices
    2. Double barrier methods (e.g. condom or diaphragms with spermicidal gel or foam)
    3. 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.

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;
  • 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;
  • Current use of ergot preparations, methysergide, B-adrenergic antagonists, contraceptives containing female steroid hormones, cyclosporine, clonidine, nicotine and cocaine;
  • Pregnant or lactating female;
  • Has known exaggerated pharmacological sensitivity or hypersensitivity to any drug similar to Alprostadil or its excipients;
  • Has known hypersensitivity to nitrile;
  • Involvement in any investigational drug or device study within 30 days prior to screening;
  • History of non-compliance with treatment or clinic visit attendance.

Sites / Locations

  • Diagnamics, Inc.
  • University of Michigan Scleroderma Program - Division of Rheumatology/Dept. of Internal Medicine
  • Cleveland Clinic
  • Scleroderma Research Center - University of Pittsburgh School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Alprostadil Cream (300mcg)

Alprostadil Cream (1000mcg)

Alprostadil Cream (3000mcg)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Pharmacodynamic evaluation: digital perfusion by laser Doppler capillary velocimetry and on digital temperature recovery with thermography.
Safety assessments based on review of adverse events, vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests.

Secondary Outcome Measures

Full Information

First Posted
August 20, 2014
Last Updated
March 21, 2016
Sponsor
NexMed (U.S.A.), Inc. (subsidiary of Apricus Biosciences, Inc.)
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1. Study Identification

Unique Protocol Identification Number
NCT02228850
Brief Title
Study of Acute Peripheral Vascular Effects, Safety and Tolerability in Subjects With Raynaud's Phenomenon Secondary to Systemic Sclerosis
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
November 2014 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NexMed (U.S.A.), Inc. (subsidiary of Apricus Biosciences, Inc.)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alprostadil Cream (300mcg)
Arm Type
Experimental
Arm Description
300 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, one dispenser for each administration
Arm Title
Alprostadil Cream (1000mcg)
Arm Type
Experimental
Arm Description
1000 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, one dispenser for each administration
Arm Title
Alprostadil Cream (3000mcg)
Arm Type
Experimental
Arm Description
3000 micrograms/.42% Alprostadil Cream with 2.5% Dodecyl-2-N,N-dimethylaminopropionate hydrochloride (DDAIP-HCl) and Placebo, two dispensers for each administration
Intervention Type
Drug
Intervention Name(s)
Alprostadil
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
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
Title
Safety assessments based on review of adverse events, vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests.
Time Frame
One month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
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; 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. 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; 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; Current use of ergot preparations, methysergide, B-adrenergic antagonists, contraceptives containing female steroid hormones, cyclosporine, clonidine, nicotine and cocaine; Pregnant or lactating female; Has known exaggerated pharmacological sensitivity or hypersensitivity to any drug similar to Alprostadil or its excipients; Has known hypersensitivity to nitrile; Involvement in any investigational drug or device study within 30 days prior to screening; History of non-compliance with treatment or clinic visit attendance.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara Troupin, MD, MBA
Organizational Affiliation
NEXMED (U.S.A.), Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Diagnamics, Inc.
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Facility Name
University of Michigan Scleroderma Program - Division of Rheumatology/Dept. of Internal Medicine
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Scleroderma Research Center - University of Pittsburgh School of Medicine
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States

12. IPD Sharing Statement

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

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