A Phase 1, Randomized, Double Blind, Placebo Controlled, Dose Escalation, and Bioavailability Study Evaluating the Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Subjects With Cystic Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 163
- 主要终点
- Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
Evaluate the safety and tolerability of VX-659 in healthy subjects
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
- Triple (Participant, 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
- 是
入选标准
- •Healthy Volunteers: PARTS A, B, and C
- •Males and Females of non-childbearing potential.
- •Between the ages of 18 and 60 years inclusive
- •Healthy, as defined per protocol.
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive
- •Body weight >50 kg
- •CF Patients: PART D
- •Body weight ≥35 kg.
- •Males and Females of non-childbearing potential.
- •Sweat chloride value ≥ 60 mmol/L at screening.
- •Heterozygous for F508del and a minimal function CFTR mutation
- •Forced expiratory volume in 1 second (FEV1) ≥40% and ≤90% of predicted at screening
排除标准
- •Healthy Volunteers: PARTS A, B, and C
- •History of any illness or any clinical condition that in the opinion of the investigator might confound the results of the study or pose additional risk to the subject.
- •Any condition possibly affecting drug absorption.
- •History of febrile illness within 14 days before the first study drug dose.
- •Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
- •CF Patients: PART D
- •History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject.
- •History of cirrhosis with portal hypertension.
- •Risk factors for Torsade de Pointes.
- •G6PD deficiency assessed at Screening.
- •Abnormal Laboratory Values.
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •History of solid organ or hematological transplantation.
研究组 & 干预措施
Part A: VX-659 or Matching Placebo
Part A includes single-dose escalation.
干预措施: VX-659 (Drug)
Part A: VX-659 or Matching Placebo
Part A includes single-dose escalation.
干预措施: VX-659 Matching Placebo (Drug)
Part B: VX-659 or Matching Placebo
Part B includes multiple-dose escalation.
干预措施: VX-659 (Drug)
Part B: VX-659 or Matching Placebo
Part B includes multiple-dose escalation.
干预措施: VX-659 Matching Placebo (Drug)
Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part D includes subjects with CF. Participants will receive TC or matching placebos.
干预措施: VX-659 (Drug)
Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
干预措施: VX-659 (Drug)
Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
干预措施: Tezacaftor (Drug)
Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
干预措施: Ivacaftor (Drug)
Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
干预措施: Triple Combination (TC) Matching Placebos (Drug)
Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part D includes subjects with CF. Participants will receive TC or matching placebos.
干预措施: Tezacaftor (Drug)
Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part D includes subjects with CF. Participants will receive TC or matching placebos.
干预措施: Ivacaftor (Drug)
Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
Part D includes subjects with CF. Participants will receive TC or matching placebos.
干预措施: Triple Combination (TC) Matching Placebos (Drug)
结局指标
主要结局
Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
时间窗: from baseline up to Day 50
次要结局
- Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL)(from baseline up to Day 18)
- AUCtau of TEZ and selected metabolites (μg,h/mL)(from baseline up to Day 18)
- Ctrough of TEZ and selected metabolites (μg/mL)(from baseline up to Day 18)
- Ctrough of IVA and selected metabolites (μg/mL)(from baseline up to Day 18)
- Cmax of TEZ and selected metabolites (μg/mL)(from baseline up to Day 18)
- AUCtau of IVA and selected metabolites (μg,h/mL)(from baseline up to Day 18)
- Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL)(from baseline up to Day 18)
- Cmax of IVA and selected metabolites (μg/mL)(from baseline up to Day 18)
- Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (μg,h/mL)(from baseline up to Day 18)