A Phase I/II, Multi-center, Randomized, Placebo-Controlled, Study Designed to Assess the Safety, Tolerability, and Pharmacokinetics of PTI-428 in Subjects With Cystic Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 29
- 主要终点
- MAD: safety and tolerability as assessed by adverse events, pulomonary function tests, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs
研究概览
简要总结
This trial will consist of three arms: Part A, Part B, and Part C. Part A has two groups. The first group will enroll adult subjects with cystic fibrosis (CF) into a single ascending dose (SAD) treatment group. The second group will enroll adult subjects with CF, including those on background treatment with ORKAMBI® and those not on a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, into a multiple ascending dose (MAD) treatment group. Part B will enroll adult subjects with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months into a Phase II treatment group consisting of two cohorts. Part C will enroll adult subjects with CF, including those on background treatment with KALYDECO® and those not on a CFTR modulator, into a Phase II treatment group consisting of three cohorts. Approximately 136 subjects will be enrolled.
详细描述
PART A The SAD treatment group is comprised of 3 cohorts where subjects will be randomized to either PTI-428 or placebo. Following the conclusion of at least 3 SAD treatment groups, a set of adult subjects diagnosed with CF will participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3 cohorts. MAD Cohort 1 will enroll adult subjects with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months at the time of randomization. MAD Cohorts 2 and 3 will enroll adult subjects with CF who are not currently on any background therapies. Subjects in all MAD cohorts will be randomized to either PTI-428 or placebo. Each dose will be administered once daily (QD) for a total of 7 Days.
PART B Following the conclusion of MAD Cohort 1, a set of adult subjects diagnosed with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months will participate in Part B. The Part B Phase II treatment group is comprised of 2 cohorts where subjects will be randomized to either PTI-428 or placebo. Each dose will be administered QD for a total of 28 days.
PART C Following the conclusion of Part B Phase II, a set of adult subjects diagnosed with CF will participate in Part C. The Part C Phase II treatment group is comprised of 3 cohorts. Part C Cohort 1 will enroll adult subjects with CF who are eligible to take, but not currently taking, ORKAMBI® in accordance with the approved label. Part C Cohort 2 will enroll adult subjects with CF currently on stable KALYDECO® background therapy for a minimum of 3 months at the time of randomization. Part C Cohort 3 will enroll adult subjects with CF who are not currently on any background therapies and are pancreatic sufficient. Each PTI-428 or placebo dose will be administered QD for a total of 28 days.
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
- •Confirmed diagnosis of CF.
- •Forced expiratory volume in 1 second (FEV1) 40-90% predicted.
- •Non-smoker and non-tobacco user for a minimum of 30 days prior to screening and for the duration of the study.
排除标准
- •Participation in another clinical trial or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer, prior to Study Day
- •History of cancer within the past five years (excluding cervical CIS with curative therapy for at least one year prior to screening and non-melanoma skin cancer).
- •History of organ transplantation.
- •Any sinopulmonary infection or CF exacerbation requiring a change or addition of medication (including antibiotics) within 1 month of Study Day 1 or any other clinically significant infection as determined by the investigator within 1 month of Day
- •History of alcohol or drug abuse or dependence within 12 months of screening as determined by the Investigator.
- •Male and female of child-bearing potential, unless they are using highly effective methods of contraception during participation in the clinical study and for 4 weeks after termination from study.
- •Pregnant or nursing women.
研究组 & 干预措施
Part A
Part A consists of two treatment groups, SAD and MAD. Both treatment groups will consist of 3 cohorts. In SAD, subjects will receive a single dose of PTI-428 or placebo. In MAD, subjects will receive once daily dosing of PTI-428 or placebo for 7 days.
干预措施: PTI-428 (Drug)
Part A
Part A consists of two treatment groups, SAD and MAD. Both treatment groups will consist of 3 cohorts. In SAD, subjects will receive a single dose of PTI-428 or placebo. In MAD, subjects will receive once daily dosing of PTI-428 or placebo for 7 days.
干预措施: Placebo (Drug)
Part B
Part B will consist of 2 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days.
干预措施: PTI-428 (Drug)
Part B
Part B will consist of 2 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days.
干预措施: Placebo (Drug)
Part C
Part C will consist of 3 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days.
干预措施: PTI-428 (Drug)
Part C
Part C will consist of 3 cohorts. Subjects will receive once daily dosing of PTI-428 or placebo for 28 days.
干预措施: Placebo (Drug)
结局指标
主要结局
MAD: safety and tolerability as assessed by adverse events, pulomonary function tests, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs
时间窗: Baseline to Day 14
Part B and Part C Cohorts 2 and 3: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs
时间窗: Baseline to Day 35
Part C Cohort 1: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs
时间窗: Baseline to Day 49
SAD: safety and tolerability as assessed by adverse events, safety labs: hematology, chemistry, and urinalysis, electrocardiograms (ECGs), physical examinations, and vital signs
时间窗: Baseline to Day 7
次要结局
- Part C Cohort 1: AUC0-t of multiple oral doses(Baseline through Day 42)
- Part C Cohort 1: AUC0-∞ of multiple oral doses(Baseline through Day 42)
- Part C Cohort 1: change in FEV1 over time(Baseline through Day 49)
- SAD: apparent terminal half-life (t1/2) of single oral dose(Baseline through 72 hours post dose)
- SAD: time to reach maximum plasma concentration (Tmax) of single oral dose(Baseline through 72 hours post dose)
- SAD: maximum plasma concentration (Cmax) of single oral dose(Baseline through 72 hours post dose)
- Part B and Part C Cohorts 2 and 3: change in weight over time(Baseline through Day 35)
- SAD: area under the concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of single oral dose(Baseline through 72 hours post dose)
- MAD: t1/2 of multiple oral doses(Baseline through 24 hours post Day 7 dose)
- MAD: Tmax of multiple oral doses(Baseline through 24 hours post Day 7 dose)
- MAD: Cmax of multiple oral doses(Baseline through 24 hours post Day 7 dose)
- Part C Cohort 1: t1/2 of multiple oral doses(Baseline through Day 42)
- Part C Cohort 1: Tmax of multiple oral doses(Baseline through Day 42)
- Part C Cohort 1: Cmax of multiple oral doses(Baseline through Day 42)
- MAD: AUC0-t of multiple oral doses(Baseline through 24 hours post Day 7 dose)
- MAD: area under the concentration-time curve from time 0 to infinity (AUC0-∞) of multiple oral doses(Baseline through 24 hours post Day 7 dose)
- Part B and Part C Cohorts 2 and 3: t1/2 of multiple oral doses(Baseline through 24 hours post Day 28 dose)
- Part B and Part C Cohorts 2 and 3: Tmax of multiple oral doses(Baseline through 24 hours post Day 28 dose)
- Part B and Part C Cohorts 2 and 3: Cmax of multiple oral doses(Baseline through 24 hours post Day 28 dose)
- Part B and Part C Cohorts 2 and 3: AUC0-t of multiple oral doses(Baseline through 24 hours post Day 28 dose)
- Part B and Part C Cohorts 2 and 3: AUC0-∞ of multiple oral doses(Baseline through 24 hours post Day 28 dose)
- Part B and Part C Cohorts 2 and 3: change in forced expiratory volume in one second (FEV1) over time(Baseline through Day 35)
- Part B and Part C Cohorts 2 and 3: change in sweat chloride over time(Baseline through Day 35)
- Part C Cohort 1: change in sweat chloride over time(Baseline through Day 49)
- Part C Cohort 1: change in weight over time(Baseline through Day 49)