Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine

NCT ID: NCT00775463

Last Updated: 2023-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2011-07-31

Brief Summary

This study will evaluate the effect of treprostinil diethanolamine (UT-15C) sustained release tablets(compared to placebo) on digital ulcers in patients with scleroderma. Treprostinil diethanolamine is an analog of prostacyclin. Prostacyclin is a naturally occuring substance produced by the cells of blood vessels that inhibits platelet aggregation, induces vasodilation, and suppresses smooth muscle proliferation. Improvement in blood flow in lower limbs and fingers would be anticipated to result in a reduction in ischemic pain, Raynaud's phenomenon and promote healing of digital ulcers and other ischemic wounds.

Conditions

Systemic Sclerosis; Scleroderma

Keywords

Scleroderma, Diffuse; Scleroderma, Limited; Scleroderma, Systemic; Ulcer; prostacyclin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

treprostinil diethanolamine

Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.

Group Type: EXPERIMENTAL

treprostinil diethanolamine

Intervention Type: DRUG

oral sustained release tablet. Maximum tolerable dose not exceeding 16 mg twice daily (BID)

placebo (sugar pill)

Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

treprostinil diethanolamine

oral sustained release tablet. Maximum tolerable dose not exceeding 16 mg twice daily (BID)

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject gave voluntary written informed consent to participate in the study
• Diagnosis of systemic sclerosis (SSc) as defined by American College of Rheumatology (ACR) criteria
• Males and females age greater than 18 years at Screening
• Presence of at least one active digital ulcer (met protocol defined qualifications for active digital ulcer) at Baseline
• Females of childbearing potential willing to use a reliable form of medically acceptable contraception and have a negative pregnancy test at Screening and Baseline
• Able to communicate effectively with study personnel and willing to comply with protocol requirements

Exclusion Criteria

• Diagnosis of pulmonary arterial hypertension (PAH)
• Body weight less than 40 kg at Screening and confirmed at Baseline
• History of postural hypotension, unexplained syncope, a blood pressure that is less than 90 mmHg systolic or 50 mmHg diastolic at Screening and Baseline
• Hemoglobin concentration less than 75% of the lower limit of the normal range at Screening
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C, or ALT greater than three times upper limit of normal
• Intractable diarrhea, or severe malabsorption, defined as greater than 15% unintentional loss of body weight in the last 6 months prior to Screening; any severe organ failure (e.g., lung, kidney), bleeding diathesis or platelet disorder, or any life-threatening condition
• Pregnant or breast-feeding
• Simultaneously fulfilled criteria for a second connective tissue disease including systemic lupus erythermatosus, rheumatoid arthritis or inflammatory myopathy
• Sympathectomy of the upper limb, involving the hand, performed within 12 months of Baseline. Sympathectomy performed on the non-target limb (hand not presenting with qualifying ulcers) or which did not include the hand, performed within 6 months of Baseline
• Receipt of prostanoid treatment (epoprostenol, treprostinil sodium, or other prostacyclin analog) within the previous 3 months of Baseline for conditions including Raynaud's phenomenon, rest pain and / or digital ulcers
• Required systemic antibiotics for infected digital ulcers within 2 weeks of Screening
• Local injection of botulinum toxin in an affected finger within 1 month prior to Baseline
• Treatment with endothelin receptor antagonists within 1 month prior to Baseline
• Patients on phosphodiasterase inhibitors, such as sildenafil or tadalafil, who have received treatment for less than 6 months prior to Baseline (unless for intermittent treatment of male erectile dysfunction)
• Treatment with statin within 1 month prior to Screening, unless for management of hyperlipidemia
• Received an investigational product within 1 month preceding Screening
• Known hypersensitivity to treprostinil diethanolamine or any of the excipients
• Tobacco or nicotine use at any level within the past 6 months prior to Screening
• Any condition or laboratory that in the opinion of the investigator might interfere with subject's participation, pose an additional risk for the subject, could prevent understanding the objectives, nature or consequences of the trial, compliance with the protocol, adherence to therapy, or that would interfere with interpretation of study assessments

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Seibold, MD

Role: PRINCIPAL_INVESTIGATOR

Scleroderma Research Consultants LLC, Avon, CT,

Locations

University of Alabama - Arthritis Clinical Intervention Program

Birmingham, Alabama, United States

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

UCLA

Los Angeles, California, United States

Stanford University School of Medicine/Palo Alto VA Health Care System

Palo Alto, California, United States

Denver Medical Center

Aurora, Colorado, United States

University of Connecticut Health Center

Farmington, Connecticut, United States

Georgetown University

Washington D.C., District of Columbia, United States

Northwestern University - Feinberg School of Medicine

Chicago, Illinois, United States

University of Indiana School of Medicine

Indianapolis, Indiana, United States

Johns Hopkins University - Division of Rheumatology

Baltimore, Maryland, United States

Boston University School of Medicine

Boston, Massachusetts, United States

University of Michigan Scleroderma Program

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

UMDNJ Clinical Research Center

New Brunswick, New Jersey, United States

North Shore-LIJ Health System

Lake Success, New York, United States

The Hospital for Special Surgery

New York, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

University of Toledo

Toledo, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Texas - Houston

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Dalhousie University - QEII Health Science Center

Halifax, Nova Scotia, Canada

St Joseph's Health Care

London, Ontario, Canada

McGill University

Montreal, Quebec, Canada

Clinical Sciences Center - University Hospital

Liverpool, , United Kingdom

Royal Free Hospital - Center for Rheumatology

London, , United Kingdom

Salford Royal Hospital

Manchester, , United Kingdom

Countries

United States; Canada; United Kingdom

References

Mecoli CA, Perin J, Van Eyk JE, Zhu J, Fu Q, Allmon AG, Rao Y, Zeger S, Wigley FM, Hummers LK, Shah AA. Vascular biomarkers and digital ulcerations in systemic sclerosis: results from a randomized controlled trial of oral treprostinil (DISTOL-1). Clin Rheumatol. 2020 Apr;39(4):1199-1205. doi: 10.1007/s10067-019-04863-0. Epub 2019 Dec 19.

Reference Type: DERIVED

PMID: 31858338 (View on PubMed)

Other Identifiers

TDE-DU-201

Identifier Type: -

Identifier Source: org_study_id