Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine
Condition: Systemic Sclerosis; Scleroderma
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized
Intervention: treprostinil diethanolamine; placebo
Intervention description: oral sustained release tablet. Maximum tolerable dose not exceeding 16 mg twice daily (BID)
Intervention MeSH terms: Treprostinil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 148.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Scleroderma, Diffuse; Scleroderma, Limited; Scleroderma, Systemic; Ulcer; prostacyclin

Summary:

      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.
    

Eligibility criteria:

        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