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Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis (DISTOL-PK)
This study is currently recruiting participants.
Verified by United Therapeutics, February 2009
First Received: February 19, 2009   No Changes Posted
Sponsored by: United Therapeutics
Information provided by: United Therapeutics
ClinicalTrials.gov Identifier: NCT00848939
  Purpose

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 Intervention Phase
Systemic Sclerosis
Drug: treprostinil diethanolamine
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Pharmacokinetics Study
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

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • adverse event monitoring [ Time Frame: Cohort 1:Day 0 to Day 2; Cohort 2: Day 0 to Day 47 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • clinical laboratories [ Time Frame: Cohort 1: Day 0 and Day 2; Cohort 2: Day 0 and Day 47 ] [ Designated as safety issue: Yes ]
  • Cohort 2: Raynauds Phenomenon Visual Analoge Scale [ Time Frame: 7 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: December 2008
Arms Assigned Interventions
treprostinil diethanolamine: Experimental 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00848939

Locations
United States, Maryland
Johns Hopkins Scleroderma Center Not yet recruiting
Baltimore, Maryland, United States, 21224
Contact: Cyndi Anderson, MS     410-550-8582     canderson@jhmi.edu    
Principal Investigator: Fred Wigley, MD            
United States, Massachusetts
Boston University School of Medicine Rheumatology Arthritis Center Not yet recruiting
Boston, Massachusetts, United States, 02118
Contact: Fei-Ying Cheong     617-638-4344     fycheong@bu.edu    
Principal Investigator: Robert Simms, MD            
United States, Michigan
University of Michigan Scleroderma Program Recruiting
Ann Arbor, Michigan, United States, 48016
Contact: Terry Thielan     734-936-4009     tthielan@med.umich.edu    
Principal Investigator: Elena Tishkowski, MD            
Sponsors and Collaborators
United Therapeutics
Investigators
Study Director: Kristan Rollins, PharmD United Therapeutics
  More Information

No publications provided

Responsible Party: United Therapeutics ( Kristan Rollins, PharmD Clinical Research Scientist )
Study ID Numbers: TDE-DU-101
Study First Received: February 19, 2009
Last Updated: February 19, 2009
ClinicalTrials.gov Identifier: NCT00848939     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by United Therapeutics:
systemic sclerosis
scleroderma
pharmacokinetics
treprostinil diethanolamine

Study placed in the following topic categories:
Skin Diseases
Treprostinil
Connective Tissue Diseases
Scleroderma
Scleroderma, Diffuse
Sclerosis
Scleroderma, Systemic
Cardiovascular Agents
Antihypertensive Agents

Additional relevant MeSH terms:
Pathologic Processes
Skin Diseases
Therapeutic Uses
Treprostinil
Connective Tissue Diseases
Scleroderma, Diffuse
Sclerosis
Scleroderma, Systemic
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 30, 2009