Pharmacokinetics of Oral Treprostinil in Patients With Systemic Sclerosis

• Status: Completed
• Trial end date: 2010-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: United Therapeutics
• Treatments: Treprostinil

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.