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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT00848939
First received: February 19, 2009
Last updated: October 19, 2012
Last verified: October 2012
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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

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 ]

Enrollment: 28
Study Start Date: December 2008
Study Completion Date: April 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00848939

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

No publications provided

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00848939     History of Changes
Other Study ID Numbers: TDE-DU-101
Study First Received: February 19, 2009
Last Updated: October 19, 2012
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on July 29, 2014