Open-Label Study of Oral Treprostinil in Digital Ulcers (DISTOL-EXT)

Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine: An Open-label Multicenter Extension Study

This open label extension trial will allow ongoing treatment of subjects who participated in the randomized controlled trials, and will provide long term information about the safety of treprostinil diethanolamine SR in subjects with SSc and digital ulcers.

Study Overview

• Status: Terminated
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Drug: treprostinil diethanolamine

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • St Joseph's Health Care
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital - Center for Rheumatology
  • Manchester, United Kingdom, M13 9PT
    • Salford Royal Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-7201
      • University of Alabama - Birmingham - Arthritis Clinical Intervention Program
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • Los Angeles, California, United States, 90095-1670
      • UCLA
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Centre
  • Connecticut
    • Farmington, Connecticut, United States, 06030-1310
      • University of Connecticut Health Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University - Dept. of Medicine/Rheumatology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University - Feinberg School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University - Division of Rheumatology
  • Massachusetts
    • Boston, Massachusetts, United States, 02118-2526
      • Boston University School of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan - Scleroderma Program
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • UMDNJ Clinical Research Center
  • New York
    • Lake Success, New York, United States, 11042
      • North Shore - LIJ Health System
    • New York, New York, United States, 10021
      • The Hospital for Special Surgery
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Toledo, Ohio, United States, 43614
      • University of Toledo
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425-8900
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas - Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible subjects who completed assessments for the final visit of the previous TDE-DU-201 controlled trial and who signed appropriate informed consent were eligible to enroll in this extension study.
• If a female of childbearing potential, the subject must have agreed to continue practicing an acceptable method of birth control (i.e., surgical sterilization, approved hormonal contraceptives, barrier methods [such as a condom or diaphragm] used with a spermicide, or an intrauterine device).

Exclusion Criteria:

• Have had any change in clinical status that, in the opinion of the Investigator, would pose a safety risk for participation in this extension study;
• Have been found to be unable to complete study assessments in the previous controlled trial;
• Have prematurely discontinued study drug during the previous study due to clinical worsening or treatment related adverse events.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treprostinil; Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose (MTD).	Drug: treprostinil diethanolamine; sustained release tablet; BID dosing; up to 16 mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net Ulcer Burden- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment	Net ulcer burden at any given assessment was defined as the number of "new" or "active" ulcers at that assessment, plus the number of "indeterminate" ulcers at that assessment that had previously been classified as either "active" or "new" at any earlier assessment during the study. The mean change in net ulcer burden from time of study entry was summarized for each scheduled visit assessment.	Baseline and Months 1, 3, 6, 9, 12, and 18
Total Ulcer Number- Mean Change From Time of Study Entry for Each Scheduled Visit Assessment	The total ulcer number includes all ulcers designated as "active", "indeterminate", or "new" for a given visit. The mean change in the total number of ulcers present from time of study entry was summarized for each scheduled visit assessment.	Baseline and Months 1, 3, 6, 9, 12, and 18
Formation of New Ulcers	The number and percentage of subjects who developed new ulcers during the study were summarized.	18 months (or last study visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Function and QOL Measure: Scleroderma Health Assessments Questionnaire (SHAQ)- Mean Change From Study Entry in SHAQ Component Scores at Each Scheduled Assessment	The SHAQ consists of 20 health assessment questionnaire questions with integer responses of 0 (without any difficulty) to 3 (unable to do), and five scleroderma-specific visual analog scale (VAS) domains (Overall Disease Activity, Raynaud's Phenomenon, Finger Ulcers, Breathing, and Intestinal Problems) with values ranging from 0.0 to 15.0 centimeters. The questions are divided into eight component domains: Dressing & Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each domain score is calculated by summing the domain responses and dividing by the number of questions in that domain. Each VAS domain score is calculated by dividing the value in centimeters by 5. SHAQ component and VAS domain score ranges from 0 (least limitation) to 3 (most limitation). The aggregate SHAQ score is calculated by dividing the sum of all domain scores by 13, with a score ranging from 0 (least limitation) to 3 (most limitation).	Baseline and Months 1, 3, 6, and 12
Patient Function and Quality of Life Measure: Cochin Hand Function Scale (CHFS)-Mean Change From Study Entry in CHFS Score at Each Scheduled Assessment	The CHFS score is derived from 18 validated questions that assess functional disability and handicap due to hand involvement in rheumatoid arthritis. Each answer is scored on a scale with possible integer responses of 0(without difficulty) to 5 (impossible). The CHFS score is simply the sum of all 18 questions, divided by the number of questions actually answered, multiplied by 18. At least 10 of the 18 questions must have been answered in order for CHFS to be calculated. Therefore, CHFS score values can range from 0 (least limitation) to 90 (most limitation), with improvements in function or reduction of limitation indicated a decreased score value. The mean change from study entry in CHFS scores at each scheduled assessment are summarized.	Baseline and Months 1, 3, 6, and 12

Collaborators and Investigators

• Sponsor: United Therapeutics
• Investigators: Principal Investigator: James Seibold, MD, Scleroderma Research Consultants LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: February 16, 2009
• First Submitted That Met QC Criteria: February 19, 2009
• First Posted (Estimate): February 20, 2009

Study Record Updates

• Last Update Posted (Estimate): February 7, 2014
• Last Update Submitted That Met QC Criteria: January 8, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: systemic sclerosis; scleroderma; digital ulcers; vasculopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-DU-202