An Open-label Study, to Assess the Long-term Safety and Clinical Benefit of Droxidopa in Subjects With PAF, Dopamine Beta Hydroxylase Deficiency or Non-diabetic Neuropathy and Symptomatic Neurogenic Orthostatic Hypotension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 103
- 试验地点
- 54
- 主要终点
- Change in Orthostatic Hypotension Questionnaire Composite Score (OHQ)
研究概览
简要总结
The purpose of this study is to assess the durability of effect of Droxidopa in treating symptoms of neurogenic orthostatic hypotension in patients with Primary Autonomic Failure (Pure Autonomic Failure, Multiple System Atrophy, Parkinson's Disease), Non-diabetic neuropathy, or Beta Hydroxylase deficiency.
详细描述
Systolic blood pressure is transiently and minimally decreased in healthy individuals upon standing. Normal physiologic feedback mechanisms work through neurally-mediated pathways to maintain the standing blood pressure, and thus maintain adequate cerebral perfusion. The compensatory mechanisms that regulate blood pressure upon standing are dysfunctional in subjects with orthostatic hypotension (OH), a condition that may lead to inadequate cerebral perfusion with accompanying symptoms of syncope, dizziness or lightheadedness, unsteadiness and blurred or impaired vision, among other symptoms.
The autonomic nervous system has a central role in the regulation of blood pressure. Primary Autonomic Failure is manifested in a variety of syndromes. Orthostatic hypotension is a usual presenting symptom. Primary Autonomic Failure may be the primary diagnosis, and classifications include pure autonomic failure (PAF), also called idiopathic orthostatic hypotension (Bradbury-Eggleston syndrome) autonomic failure with multiple system atrophy (Shy-Drager syndrome) and also Parkinson's disease. Regardless of the primary condition, autonomic dysfunction underlies orthostatic hypotension.
Orthostatic hypotension may be a severely disabling condition which can seriously interfere with the quality of life of afflicted subjects. Currently available therapeutic options provide some symptomatic relief in a subset of subjects, but are relatively ineffective and are often accompanied by severe side effects that limit their usefulness. Support garments (tight-fitting leotard) may prove useful in some subjects, but is difficult to don without family or nursing assistance, especially for older subjects. Midodrine, fludrocortisone, methylphenidate, ephedrine, indomethacin and dihydroergotamine are among some of the pharmacological interventions that have been used to treat orthostatic hypotension, although only midodrine is specifically approved for this indication. The limitations of these currently available therapeutic options, and the incapacitating nature and often progressive downhill course of disease, point to the need for an improved therapeutic alternative.
The current withdrawal design study will measure the efficacy of droxidopa on symptoms of neurogenic orthostatic hypotension in patients randomized to continued droxidopa treatment versus placebo, following 14 days of double-blind treatment.
Droxidopa
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •To be eligible for inclusion, each patient must fulfill the following criteria:
- •Participated in Droxidopa Protocol 302;
- •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.
排除标准
- •Patients are not eligible for this study if they fulfill one or more of the following criteria:
- •Currently taking ephedrine or midodrine;
- •Patients taking ephedrine or midodrine must stop taking these drugs at least 2 days prior to their study entry visit (Visit 1).
- •Currently taking anti-hypertensive medication;
- •* The use of short-acting anti-hypertensive medications at bedtime is permitted.
- •Currently taking tri-cyclic antidepressant medication or other norepinephrine re-uptake inhibitors;
- •Have changed dose, frequency and or type of prescribed medication, within two weeks of study start (excluding ephedrine and midodrine);
- •History of more than moderate alcohol consumption;
- •History of known or suspected drug or substance abuse;
- •Women of childbearing potential who are not using a medically accepted contraception;
- •Reproductive potential:
- •Female subjects should be either post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile, or women of child-bearing potential (WOCP) who are using or agree to use acceptable methods of contraception.
- •Acceptable contraceptives include intrauterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.
- •For WOCP a urine pregnancy test must be conducted at each study visit.
- •WOCP must be advised to use acceptable contraceptives throughout the study period and for 30 days after the last dose of investigational product.
- •If hormonal contraceptives are used they should be taken according to the package insert.
- •WOCP who are not currently sexually active must agree to use acceptable contraception, as defined above, if they decide to become sexually active during the period of the study and for 30 days after the last dose of investigational product.
- •Sexually active males whose partner is a WOCP and who do not agree to use condoms for the duration of the study and for 30 days after the last dose;
- •Women who are pregnant or breast feeding;
- •Known or suspected hypersensitivity to the study medication or any of its ingredients;
- •Pre-existing sustained severe hypertension (BP 180/110 mmHg in the sitting position);
- •Have atrial fibrillation or, in the investigator's opinion, have any other significant cardiac arrhythmia;
- •Any other significant systemic, hepatic, cardiac or renal illness;
- •Diabetes mellitus or insipidus;
- •Have a history of closed angle glaucoma;
- •Have a known or suspected malignancy;
- •Have a serum creatinine level > 130 umol/L;
- •Patients with known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug;
- •In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing;
- •In the investigator's opinion, are unable to adequately co-operate because of individual or family situation;
- •In the investigator's opinion, are suffering from a mental disorder that interferes with the diagnosis and/or with the conduct of the study, e.g. schizophrenia, major depression, dementia;
- •Are not able or willing to comply with the study requirements for the duration of the study.
研究组 & 干预措施
Droxidopa
Study medication
干预措施: Droxidopa (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Orthostatic Hypotension Questionnaire Composite Score (OHQ)
时间窗: 14 days
The OHQ is the average of two sub-scales, the Orthostatic Hypotension Symptom Assessment Scale (OHSA) and the Orthostatic Hypotension Daily Activities Scale (OHDAS). Each asks the patient to rate their symptoms or disease impact over the past week. The OHSA sub-scale is the average of six items: 1) Dizziness, lightheadedness, feeling faint or feeling like you might black out; 2) Problems with vision; 3) Weakness; 4) Fatigue; 5) Trouble concentrating; and 6) Head/neck discomfort. The OHDAS sub-scale is the average of four items: 1) Standing for a short time; 2) Standing for a long time; 3) Walking for a short time; and 4) Walking for a long time. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe. In this withdrawal design, a positive score indicates worsening during the double-blind randomized phase relative to value at randomization (on open-label drug). All patients are on open-label droxidopa for 3 months prior to randomization.
次要结局
- Change in Orthostatic Hypotension Daily Activities (OHDAS) Score(14 days)
- Change in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score(14 days)
- Change in Systolic Blood Pressure (SBP) Measurements 3 Minutes Post Standing(14 days)
- Patient Reported Clinical Global Impression - Severity(14 days)
- Clinician Recorded Clinical Global Impression - Severity(14 days)
- Patient Reported Clinical Global Impression - Improvement(14 days)
- Clinician Rated Clinical Global Impressions - Improvement(14 days)