NCT01934647终止1 期
A Non-randomized, Single-Panel, Open-Label Trial to Study the Safety, Tolerability and Pharmacodynamics of MK-8892 Acute Dosing in Subjects With Moderate to Severe Pulmonary Arterial Hypertension
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 主要终点
- Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892
研究概览
简要总结
This clinical trial will study the safety, tolerability, and pharmacodynamics of single doses of MK-8892 in participants with pulmonary arterial hypertension (PAH). The primary objective is to estimate the measured peak effect of the highest acutely tolerated (HAT) single oral dose of MK-8892 on pulmonary vascular resistance (PVR).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •postmenopausal female or if female of reproductive potential, remains abstinent or uses two acceptable methods of birth control during 14 days after dosing with MK-8892
- •has suspected PAH classified in one of the following sub-groups: idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease, as defined by the Dana Point 2008 Clinical Classification
- •has a clinical indication for right heart catheterization
- •PAH classified as World Health Organization (WHO) functional class II or III
排除标准
- •has a medical history indicating a secondary cause of Pulmonary Hypertension (PH) or a non-included etiology of PAH including the following tests within 6 months of Visit 1: Echo indicating significant left heart disease, valvular disease, or structural defects; function test indicating significant pulmonary disease; imaging test indicating veno-occlusive disease; perfusion scan indicating thromboembolic disease; abdominal ultrasound indicating cirrhosis; positive test for human immunodeficiency virus (HIV)
- •has persistent or permanent atrial fibrillation, significantly impaired gas exchange, history of radiation of the lung or mediastinum, hepatic or hepatobiliary disease, immunodeficiencies or latent bleeding risk
- •has estimated Glomerular Filtration Rate (GFR) <45 mL/min
- •has alanine aminotransferase test (ALT) serum glutamic pyruvic transaminase (SGPT) or aspartate aminotransferase test (AST) serum glutamic oxaloacetic transaminase (SGOT) >= 3 x upper limit of normal (ULN) at Visit 1
- •has a systolic blood pressure (BP) <105 mmHg, or heart rate (HR) > 100 beats/min at Visit 1 (Day -7 to -1)
- •has previously received specific therapy for PAH within 4 weeks prior to Visit 1
- •has taken sildenafil, valdenafil or a nitrate within 24 hours prior to Visit 2 date
- •has taken tadalafil within 7 days prior to Visit 2 date
- •has taken 2 or more specific PAH medications concomitantly within 4 weeks of anticipated Visit 2 date. Only treatment naïve subjects or subjects on stable PAH-specific monotherapy with an endothelin receptor antagonist ([ERA]; bosentan, ambrisentan, or macitentan) or a prostacyclin analog ([PCA]; treprostinil, epoprostenol, or iloprost) are eligible. PAH monotherapy with one of these medications may continue without interruption during this study
- •has taken a soluble guanylate cyclase (sGC) activator (riociguat) within 24 hours of anticipated Visit 2 date.
- •has taken diltiazem immediate release within 1 day or diltiazem extended release within 2 days prior to Visit 2 date
- •is currently taking potent inhibitors or inducers of Cytochrome P450 3A4 (CYPA4), or is consuming >1 liter of grapefruit juice per day
- •is pregnant or breastfeeding or expecting to conceive during study or post study follow-up period
- •has donated 500 mL of blood within prior 60 days
- •is currently participating in or has within the prior three months participated in a study with an investigational compound or device
研究组 & 干预措施
1 mg MK-8892
Experimental
Participants will receive a single oral dose of 1 mg MK-8892.
干预措施: MK-8892 (Drug)
4 mg MK-8892
Experimental
Participants will receive a single oral dose of 4 mg MK-8892.
干预措施: MK-8892 (Drug)
8 mg MK-8892
Experimental
Participants will receive a single oral dose of 8 mg MK-8892.
干预措施: MK-8892 (Drug)
结局指标
主要结局
Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892
时间窗: Baseline and up to 5 hours post-dose
PVR assessments were performed throughout the right heart catheterization (RHC). Peak PVR reduction was determined to occur if 2 consecutive PVR measurements were at least 20% greater than the nadir PVR measurement.
次要结局
未报告次要终点
研究者
相似试验
已完成
1 期
Pharmacokinetic and Safety Study of Subcutaneous and Intravenous Anifrolumab Delivered in Healthy Adult ParticipantsHealthy VolunteersNCT06662123AstraZeneca24
已完成
1 期
Study of GSK3511294 in Healthy Chinese ParticipantsAsthmaNCT05140200GlaxoSmithKline20
已完成
1 期
A Pharmacokinetics and Tolerability Study of Fedratinib in Subjects With Moderate and Severe Hepatic ImpairmentHealthy VolunteersHepatic ImpairmentNCT03983161Celgene39
已完成
1 期
Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected With Pseudomonas AeruginosaCystic FibrosisNCT00638365Humanigen, Inc.27
已完成
1 期
Study of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors (MK-4464-001)Advanced/Metastatic Solid TumorsNeoplasmsNCT05514444Merck Sharp & Dohme LLC64