Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine

DISTOL-1: Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine: A Randomized, Double-blind, Placebo-controlled, Multicenter Study

This study will evaluate the effect of treprostinil diethanolamine (UT-15C) sustained release tablets(compared to placebo) on digital ulcers in patients with scleroderma. Treprostinil diethanolamine is an analog of prostacyclin. Prostacyclin is a naturally occuring substance produced by the cells of blood vessels that inhibits platelet aggregation, induces vasodilation, and suppresses smooth muscle proliferation. Improvement in blood flow in lower limbs and fingers would be anticipated to result in a reduction in ischemic pain, Raynaud's phenomenon and promote healing of digital ulcers and other ischemic wounds.

Inclusion Criteria:

• Subject gave voluntary written informed consent to participate in the study
• Diagnosis of systemic sclerosis (SSc) as defined by American College of Rheumatology (ACR) criteria
• Males and females age greater than 18 years at Screening
• Presence of at least one active digital ulcer (met protocol defined qualifications for active digital ulcer) at Baseline
• Females of childbearing potential willing to use a reliable form of medically acceptable contraception and have a negative pregnancy test at Screening and Baseline
• Able to communicate effectively with study personnel and willing to comply with protocol requirements

Exclusion Criteria:

• Diagnosis of pulmonary arterial hypertension (PAH)
• Body weight less than 40 kg at Screening and confirmed at Baseline
• History of postural hypotension, unexplained syncope, a blood pressure that is less than 90 mmHg systolic or 50 mmHg diastolic at Screening and Baseline
• Hemoglobin concentration less than 75% of the lower limit of the normal range at Screening
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C, or ALT greater than three times upper limit of normal
• Intractable diarrhea, or severe malabsorption, defined as greater than 15% unintentional loss of body weight in the last 6 months prior to Screening; any severe organ failure (e.g., lung, kidney), bleeding diathesis or platelet disorder, or any life-threatening condition
• Pregnant or breast-feeding
• Simultaneously fulfilled criteria for a second connective tissue disease including systemic lupus erythermatosus, rheumatoid arthritis or inflammatory myopathy
• Sympathectomy of the upper limb, involving the hand, performed within 12 months of Baseline. Sympathectomy performed on the non-target limb (hand not presenting with qualifying ulcers) or which did not include the hand, performed within 6 months of Baseline
• Receipt of prostanoid treatment (epoprostenol, treprostinil sodium, or other prostacyclin analog) within the previous 3 months of Baseline for conditions including Raynaud's phenomenon, rest pain and / or digital ulcers
• Required systemic antibiotics for infected digital ulcers within 2 weeks of Screening
• Local injection of botulinum toxin in an affected finger within 1 month prior to Baseline
• Treatment with endothelin receptor antagonists within 1 month prior to Baseline
• Patients on phosphodiasterase inhibitors, such as sildenafil or tadalafil, who have received treatment for less than 6 months prior to Baseline (unless for intermittent treatment of male erectile dysfunction)
• Treatment with statin within 1 month prior to Screening, unless for management of hyperlipidemia
• Received an investigational product within 1 month preceding Screening
• Known hypersensitivity to treprostinil diethanolamine or any of the excipients
• Tobacco or nicotine use at any level within the past 6 months prior to Screening
• Any condition or laboratory that in the opinion of the investigator might interfere with subject's participation, pose an additional risk for the subject, could prevent understanding the objectives, nature or consequences of the trial, compliance with the protocol, adherence to therapy, or that would interfere with interpretation of study assessments