Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine (DISTOL-1)

• Scleroderma Health Assessment Questionnaire (SHAQ) and other functional and quality of life scales [ Time Frame: Through week 20 ] [ Designated as safety issue: No ]
• modified Rodnan Skin Score (mRSS) [ Time Frame: Baseline and week 20 ] [ Designated as safety issue: No ]
• serum biomarkers [ Time Frame: Baseline and week 20 ] [ Designated as safety issue: No ]
• adverse events [ Time Frame: Throughout week 20 ] [ Designated as safety issue: Yes ]

• Digital ulcer related pain as measured by Visual Analogue Scale (VAS) [ Time Frame: Baseline, Week 5, 10, 15 and 20 ] [ Designated as safety issue: No ]
• Raynaud's Condition Score (RCS) [ Time Frame: weeks 5, 10, 15 and 20 ] [ Designated as safety issue: No ]
• Short Form McGill Pain Questionnaire (SF-MPQ) [ Time Frame: Baseline, week 5, 10, 15 and 20 ] [ Designated as safety issue: No ]
• Scleroderma Health Assessment Questionnaire (SHAQ) [ Time Frame: Baseline, week 5, 10, 15 and 20 ] [ Designated as safety issue: No ]
• Cochin Hand Function Scale (CHFS) [ Time Frame: Baseline, week 5, 10, 15 and 20 ] [ Designated as safety issue: No ]
• modified Rodnan Skin Score (mRSS) [ Time Frame: Baseline and week 20 ] [ Designated as safety issue: No ]
• SF-36 [ Time Frame: Baseline, week 5, 10, 15, and 20 ] [ Designated as safety issue: No ]
• patient and physician digital ulcer Visual Analogue Scales (VAS) [ Time Frame: Baseline, week 5, 10, 15 and 20 ] [ Designated as safety issue: No ]
• serum biomarkers [ Time Frame: Baseline and week 20 ] [ Designated as safety issue: No ]
• adverse events [ Time Frame: Throughout week 20 ] [ Designated as safety issue: Yes ]

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.

• Systemic Sclerosis
• Scleroderma

• Drug: treprostinil diethanolamine
  oral sustained release tablet. Maximum tolerable dose not exceeding 16 mg twice daily (BID)
• Drug: placebo

• Experimental: treprostinil diethanolamine
  Intervention: Drug: treprostinil diethanolamine
• Placebo Comparator: placebo (sugar pill)
  Intervention: Drug: placebo

Inclusion Criteria:

• Subject gives 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
• Presence of at least one active digital ulcer (meets protocol defined qualifications for active digital ulcer)
• Females of childbearing potential must be willing to use a reliable form of medically acceptable contraception and have a negative pregnancy test
• 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
• 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
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
• 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.
• 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. Sympathectomy performed on the non-target limb (hands 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 Reynaud'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 use at any level within the past 6 months prior to Screening.