pharmacokinetics of oral treprostinil in patients with systemic sclerosis

Conditions: Systemic Sclerosis

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.


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.

Keywords: systemic sclerosis scleroderma pharmacokinetics treprostinil diethanolamine