RESTORE: A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 453
- 试验地点
- 167
- 主要终点
- Time To Intervention
研究概览
简要总结
To evaluate the time to treatment intervention in patients with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Pure Autonomic Failure (PAF), Non-Diabetic Autonomic Neuropathy (NDAN) or Dopamine Beta Hydroxylase (DBH) Deficiency who have been previously stabilized with droxidopa therapy for symptoms of neurogenic orthostatic hypotension (NOH) (dizziness, light-headedness, or feelings that they are about to black out)
详细描述
This is a multi-site, placebo-controlled, double-blind, randomized withdrawal, time to intervention study with a duration of up to 36 weeks, consisting of 5 periods:
Screening Period: up to 4 weeks duration; Open-Label Titration Period (Titration Period): up to 4 weeks duration; Open-Label Treatment Period (Open-Label Period): 12 weeks duration; Double-Blind Treatment Period (Double-Blind Period): 12 weeks duration; Safety Follow-Up Period: 4 weeks duration
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
- •18 years or older and able to stand (with or without limited assistance)
- •Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA or PAF) or NDAN or DBH Deficiency
- •Score of at least 4 or greater on Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 (measured at Screening [Visit 1] and the first Titration Visit [Visit 2a] prior to dosing)
- •A documented drop of at least 20 millimeters of mercury (mmHg) in SBP, within 3 minutes of standing. This can either be documented in the patient history or assessed during Screening prior to the first Titration Visit (Visit 2a)
- •Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care
- •Additional inclusion criteria for patients taking prescribed droxidopa prior to study entry:
- •Patients who are taking prescribed droxidopa therapy are eligible to participate in the study if they meet the other inclusion criteria and also have been on a stable dose of prescribed droxidopa for at least 2 weeks prior to the Screening Visit (Visit 1). In addition, they must meet either of the following at the Screening Visit (Visit 1):
- •The patient's Visit 1 OHSA Item #1 score is ≥ 7 AND the prescribed dose is ≤ 300 mg three times daily (TID); OR
- •The patient's Visit 1 OHSA Item #1 score is ≤6 AND worsens by ≥ 2 units when retested after washing out of droxidopa for at least 3 days
排除标准
- •In the investigator's opinion, the patient is not able to understand or cooperate with study procedures
- •Known or suspected alcohol or substance use disorder within the past 12 months (DSM-5 criteria)
- •Women who are pregnant or breastfeeding
- •Women of childbearing potential (WOCP) who are not using at least one method of contraception with their partner
- •Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic. Sustained is defined as the average of 3 observations each at least 10 minutes apart with the patient having been supine and at rest for at least 5 minutes prior to each measurement.
- •Untreated closed angle glaucoma
- •Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in this study)
- •Any significant uncontrolled cardiac arrhythmia
- •History of myocardial infarction or stroke, within the past 2 years
- •Current unstable angina
- •Congestive heart failure (NYHA Class 3 or 4)
- •Diabetic autonomic neuropathy
- •History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ
- •Any major surgical procedure within the past 30 days
- •Currently receiving any investigational drug or have received an investigational drug within the past 28 days
- •Additional protocol defined exclusion criteria do apply
研究组 & 干预措施
Open Label Period
Active droxidopa 100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally. During the Open Label Titration Period, patients will first receive 100 mg TID and their dose will be raised (in 100 mg increments) at subsequent visits until optimal dose is determined. During the Open Label Treatment Period, patients will receive active droxidopa100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally (equal to the patient's individual dose at the end of the Open-Label Titration Period).
干预措施: Droxidopa capsules (Drug)
Randomized Period
Active droxidopa 100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally (equal to patients individual dose at the end of the Open-Label Period) or matching placebo.
干预措施: Droxidopa capsules (Drug)
Randomized Period
Active droxidopa 100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally (equal to patients individual dose at the end of the Open-Label Period) or matching placebo.
干预措施: Placebo capsules (Drug)
结局指标
主要结局
Time To Intervention
时间窗: Randomization (Day 0) up to Week 12
Kaplan-Meier estimates are presented for time to treatment intervention. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to need for treatment intervention. Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period: * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) AND lack of efficacy as judged by the investigator; OR * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at 2 consecutive visits; OR * OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at the visit before early discontinuation; OR * participant stops IMP or withdraws from study for patient-reported lack of efficacy.
次要结局
- Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period(Randomization (Day 0) up to Week 12)
- Clinician-rated Clinical Global Impressions - Severity (CGI-S)(Weeks 2 to 12)
- Time To All-cause Discontinuation(Randomization (Day 0) up to Week 12)
- Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score(Randomization (Day 0); Weeks 2 to 12)
- Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score(Randomization (Day 0); Weeks 2 to 12)
- Participant-rated CGI-S(Weeks 2 to 12)