Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis

NCT00848939 | Completed Phase 1

• 1 other identifier: TDE-DU-101
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

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.

Conditions

Systemic Sclerosis

Keywords

systemic sclerosis; scleroderma; pharmacokinetics; treprostinil diethanolamine

Outcome Measures

Primary Outcomes (3)

• Cohort 1: treprostinil pharmacokinetics in patients with systemic sclerosis following single oral administration of a 1 mg treprostinil diethanolamine SR dose.

  pre-24hrs post dose

• 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

  0-12 hrs post-dose

• adverse event monitoring

  Cohort 1:Day 0 to Day 2; Cohort 2: Day 0 to Day 47

Secondary Outcomes (2)

• clinical laboratories

  Cohort 1: Day 0 and Day 2; Cohort 2: Day 0 and Day 47

• Cohort 2: Raynauds Phenomenon Visual Analoge Scale

  7 weeks

Study Arms (1)

treprostinil diethanolamine

EXPERIMENTAL

Drug: treprostinil diethanolamine

Interventions

treprostinil diethanolamine DRUG

Cohort 1: Single 1 mg treprostinil diethanolamine sustained release tablet dose

treprostinil diethanolamine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (3)

Johns Hopkins Scleroderma Center

Baltimore, Maryland, 21224, United States

Location

Boston University School of Medicine Rheumatology Arthritis Center

Boston, Massachusetts, 02118, United States

Location

University of Michigan Scleroderma Program

Ann Arbor, Michigan, 48016, United States

Location

Related Publications (1)

• 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.

  PMID: 23597147 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Kristan Rollins, PharmD

  United Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2009
• First Posted: February 20, 2009
• Study Start: December 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: April 1, 2010
• Last Updated: October 23, 2012

Record last verified: 2012-10

Locations

US (3)