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

Tracking Information

• First Submitted Date: February 19, 2009
• First Posted Date: February 20, 2009
• Last Update Posted Date: October 23, 2012
• Study Start Date: December 2008
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis
• 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
• 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Systemic Sclerosis

Intervention

• 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

Experimental: treprostinil diethanolamine

Interventions:

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 19, 2012): 28
• Original Estimated Enrollment (submitted: February 19, 2009): 30
• Actual Study Completion Date: April 2010
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00848939
• Other Study ID Numbers: TDE-DU-101
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: United Therapeutics
• Original Responsible Party: Kristan Rollins, PharmD Clinical Research Scientist, United Therapeutics
• Current Study Sponsor: United Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Kristan Rollins, PharmD; United Therapeutics

• PRS Account: United Therapeutics
• Verification Date: October 2012