DISTOL-1: Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine: A Randomized, Double-blind, Placebo-controlled, Multicenter Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 148
- 试验地点
- 30
- 主要终点
- Net Ulcer Burden
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
treprostinil diethanolamine
Treprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
干预措施: treprostinil diethanolamine (Drug)
placebo (sugar pill)
Matching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
干预措施: placebo (Drug)
结局指标
主要结局
Net Ulcer Burden
时间窗: Week 20
Net ulcer burden was defined as the number of "new" or "active" digital ulcers (DU), plus the number of "indeterminate" DUs at that assessment that have previously been classified as either "active" or "new" at any earlier assessment during the study. A DU was defined as an area with visually discernable depth and a loss of continuity of epithelial coverage, which could be denuded or covered by a scab or necrotic tissue. If denuded, the DU was pronounced "active." If denudation could not be judged because of the presence of scab or necrotic tissue, DU presenting with features, including underlying pain, based on Investigator clinical judgment to be consistent with loss of epithelialization, epidermis, or dermis, and requiring treatment were designated as "active." Otherwise, the DU was pronounced "indeterminate." Only DUs distal to the proximal interphalangeal joints, volar to the equator of the finger, not localized in creases and vascular in origin were assessed.
次要结局
- Short-Form McGill Pain Questionnaire(Week 20)
- Time to Ulcer Healing(Week 20)
- Patient Global Assessment of Digital Ulcer Severity VAS(Week 20)
- Modified Rodnan Skin Score (mRSS)(Week 20)
- Time to Ulcer Healing- Percentage of Subjects With Complete Healing(Week 20)
- Cochin Hand Function Scale (CHFS)(Week 20)
- Digital Ulcer Pain VAS(Week 20)
- Physician Global Assessment of Digital Ulcer Severity VAS(Week 20)
- Scleroderma Health Assessment Questionnaire (SHAQ)(Week 20)
- Patient Impression of Change (PIC) Questionnaire(Week 20)
- Short Form 36(Week 20)