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

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

Tracking Information
First Submitted Date  ICMJE February 19, 2009
First Posted Date  ICMJE February 20, 2009
Last Update Posted Date October 23, 2012
Study Start Date  ICMJE December 2008
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2009)
  • 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 ]
  • 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 ]
  • adverse event monitoring [ Time Frame: Cohort 1:Day 0 to Day 2; Cohort 2: Day 0 to Day 47 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2009)
  • clinical laboratories [ Time Frame: Cohort 1: Day 0 and Day 2; Cohort 2: Day 0 and Day 47 ]
  • Cohort 2: Raynauds Phenomenon Visual Analoge Scale [ Time Frame: 7 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Systemic Sclerosis
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: treprostinil diethanolamine
  • Drug: treprostinil diethanolamine
  • Drug: treprostinil diethanolamine
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 19, 2012)
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2009)
Actual Study Completion Date  ICMJE April 2010
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00848939
Other Study ID Numbers  ICMJE TDE-DU-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party United Therapeutics
Original Responsible Party Kristan Rollins, PharmD Clinical Research Scientist, United Therapeutics
Current Study Sponsor  ICMJE United Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kristan Rollins, PharmD United Therapeutics
PRS Account United Therapeutics
Verification Date October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP