Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis (DISTOL-PK)

• ClinicalTrials.gov Identifier: NCT00848939
• Recruitment Status: Completed
• First Posted: February 20, 2009
• Last Update Posted: October 23, 2012
• Sponsor: United Therapeutics
• Information provided by (Responsible Party): United Therapeutics

Study Description

Brief Summary:

This study will assess the pharmacokinetic and safety profile of treprostinil following fixed and escalating doses of treprostinil diethanolamine SR tablets. Open-label, two-part study assessing the pharmacokinetics, safety, and tolerability of oral treprostinil diethanolamine SR. Cohort 1: single 1 mg treprostinil diethanolamine SR dose. Cohort 2: escalating doses of treprostinil diethanolamine SR up to a target dose of 4 mg BID.

Condition or disease	Intervention/treatment	Phase
Systemic Sclerosis	Drug: treprostinil diethanolamine	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Evaluation of the Pharmacokinetics and Safety of Fixed and Escalating Doses of Oral Treprostinil Diethanolamine (UT-15C) Sustained Release Tablets in Patients With Systemic Sclerosis
• Study Start Date: December 2008
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: April 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: treprostinil diethanolamine	Drug: treprostinil diethanolamine; Cohort 1: Single 1 mg treprostinil diethanolamine sustained release tablet dose; Drug: treprostinil diethanolamine; Cohort 2: treprostinil diethanolamine sustained release doses will be escalated up to a target dose of 4 mg BID

Outcome Measures

Primary Outcome Measures :

1. Cohort 1: treprostinil pharmacokinetics in patients with systemic sclerosis following single oral administration of a 1 mg treprostinil diethanolamine SR dose. [ Time Frame: pre-24hrs post dose ]
2. Cohort 2: treprostinil pharmacokinetics at dose levels of 2 mg BID and 4 mg BID, respectively, in patients with systemic sclerosis following repeated oral administration of treprostinil diethanolamine SR tablets [ Time Frame: 0-12 hrs post-dose ]
3. adverse event monitoring [ Time Frame: Cohort 1:Day 0 to Day 2; Cohort 2: Day 0 to Day 47 ]

Secondary Outcome Measures :

1. clinical laboratories [ Time Frame: Cohort 1: Day 0 and Day 2; Cohort 2: Day 0 and Day 47 ]
2. Cohort 2: Raynauds Phenomenon Visual Analoge Scale [ Time Frame: 7 weeks ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Subject gives voluntary written informed consent to participate in the study.
• Subject has been diagnosed with systemic sclerosis (SSc) as defined by American College of Rheumatology (ACR) criteria.
• Males and females age greater than 18 years at time of Screening.
• Presence of active digital ulcer OR history of digital ulcer occurring within past 6 months at time of Screening and poorly controlled Raynaud's phenomenon (as documented by patient report of 6-10 episodes per week).
• Females of childbearing potential must be willing to use two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at Screening, confirmed at Baseline if separate visits. Women who are surgically sterile or have been post-menopausal for at least 2 years are not considered to be of child-bearing potential.
• Subject agrees to abstain from consuming grapefruit containing food or beverages for 3 days prior to Baseline and until discharge from the study.
• Subject is able to communicate effectively with study personnel and be considered reliable, willing and cooperative in terms of compliance with the protocol requirements.

Exclusion Criteria:

• Has diagnosis of pulmonary arterial hypertension and receiving approved or investigational therapies for PAH, including endothelin receptor antagonists, phosphodiesterase inhibitors, or prostacyclin analogues.
• Body weight less than 40 kg at time of Screening, confirmed at Baseline.
• The subject has a history of postural hypotension, unexplained syncope, a blood pressure that is less than 85 mmHg systolic or 50 mmHg diastolic at Screening or Baseline.
• Hemoglobin concentration less than 75% of the lower limit of the normal range at time of Screening.
• AST and/or ALT concentrations greater than 3 times upper limit of normal (ULN) at time of Screening.
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
• Intractable diarrhea, severe malabsorption, defined as greater than 15% unintentional loss of body weight in the last 6 months prior to Screening, or any severe organ failure (e.g., lung, kidney) or any life-threatening condition.
• Pregnancy or breast-feeding.
• Overlap with another connective tissue disease that could affect rest pain and hand function (e.g. diabetes mellitus, rheumatoid arthritis).
• Sympathectomy of the upper limb performed within 12 months of Baseline.
• Receipt of parenteral prostanoid treatment (epoprostenol, treprostinil sodium, or other prostacyclin analog) within the previous 3 months for conditions including PAH, rest pain and / or digital ulcers.
• Treatment with gemfibrozil, glitazones, or cyclophosphamide within 1 week prior to Baseline.
• Treatment with rifampin within 4 weeks prior to Baseline.
• Local injection of botulinum toxin in an affected finger within 1 month prior to Baseline.
• Received systemic antibiotics to treat infection of digital ulcers within 2 weeks prior to Baseline.
• Treatment with phosphodiesterase inhibitors such as sildenafil, except for intermittent treatment of male erectile dysfunction.
• Received an investigational product within 1 month preceding Screening.
• Known hypersensitivity to oral treprostinil or any of the excipients.
• Cigarette smoking at any level within the past 6 months prior to Screening.
• Any condition that could prevent compliance with the protocol or adherence to therapy.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Scleroderma Center

Baltimore, Maryland, United States, 21224

United States, Massachusetts

Boston University School of Medicine Rheumatology Arthritis Center

Boston, Massachusetts, United States, 02118

United States, Michigan

University of Michigan Scleroderma Program

Ann Arbor, Michigan, United States, 48016

Sponsors and Collaborators

United Therapeutics

Investigators

• Study Director: Kristan Rollins, PharmD; United Therapeutics

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shah AA, Schiopu E, Hummers LK, Wade M, Phillips K, Anderson C, Wise R, Boin F, Seibold JR, Wigley F, Rollins KD. Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion. Arthritis Res Ther. 2013 Apr 18;15(2):R54. doi: 10.1186/ar4216.

• Responsible Party: United Therapeutics
• ClinicalTrials.gov Identifier: NCT00848939
• Other Study ID Numbers: TDE-DU-101
• First Posted: February 20, 2009
• Last Update Posted: October 23, 2012
• Last Verified: October 2012

Keywords provided by United Therapeutics:

systemic sclerosis; scleroderma; pharmacokinetics; treprostinil diethanolamine

Additional relevant MeSH terms:

Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis; Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Treprostinil; Antihypertensive Agents