A Phase 1 / 2, Randomized, Double-Blind, Placebo-Controlled Study Designed to Evaluate the Safety, Tolerability, and Pharmacokinetics of PTI-808, PTI-801, and PTI-428 Combination Therapy in Subjects With Cystic Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 4
- 主要终点
- Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs.
研究概览
简要总结
The study is a randomized, double-blind, placebo-controlled, study that will be conducted at multiple centers in subjects with Cystic Fibrosis (CF) who are either homozygous for the F508del mutation or heterozygous with at least copy of the F508del mutation.
详细描述
Study PTI-808-02 will enroll up to approximately 32 subjects. Subjects in the first cohort will receive PTI-808 and PTI-801. Following completion of Cohort 1, initiation of enrollment into subsequent cohorts will be based upon review and approval by the Safety Review Committee (SRC).
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, Care Provider, 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
- •Cohorts 1,2 and 4: A Confirmed diagnosis of CF with the F508del/F508del CFTR genotype on record, along with clinical findings consistent with CF such as chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities
- •Cohort 3 only: Confirmed diagnosis of CF with at least one copy of the F508del CFTR mutation on record, along with clinical findings consistent with CF, such as chronic sinopulmonary disease or gastrointestinal / nutritional abnormalities
- •Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive
- •Non-smoker and non-tobacco user for a minimum of 30 days prior to screening
- •Cohort 3 only: A sweat chloride value of ≥60 mmol/L based on quantitative pilocarpine iontophoresis (as documented in the subject's medical record or as confirmed at the screening visit)
排除标准
- •Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of study drugs
- •Participation in another clinical trial or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1
- •History of cancer within the past 5 years
- •History of organ transplantation
- •Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness (as determined by the investigator) requiring an increase or addition of medication, such as antibiotics or corticosteroids, within 14 days of Day 1
- •Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme®, Cayston®, TOBI®) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1
- •History or current evidence of alcohol or drug abuse or dependence within 12 months of screening as determined by the investigator
- •Pregnant or nursing women
研究组 & 干预措施
Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
干预措施: PTI-808 (Drug)
Cohorts 1 and 2: PTI-808 Active Co-admin with PTI-801 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
干预措施: PTI-801 (Drug)
Cohorts 1 and 2: PTI-808 Placebo Co-admin with PTI-801 Placebo
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
干预措施: Placebo (Drug)
Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
干预措施: PTI-808 (Drug)
Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
干预措施: PTI-801 (Drug)
Cohort 3 PTI-808 Active + PTI-801 Active + PTI-428 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
干预措施: PTI-428 (Drug)
Cohort 3 PTI-808 placebo + PTI-801 Placebo + PTI-428 Placebo
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for a total of 14 days. A follow up visit will occur on Day 21.
干预措施: Placebo (Drug)
Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
干预措施: PTI-808 (Drug)
Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
干预措施: PTI-801 (Drug)
Cohort 4 PTI-808 Active + PTI-801 Active + PTI-428 Active
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
干预措施: PTI-428 (Drug)
Cohort 4 PTI-808 Placebo + PTI-801 Placebo + PTI-428 Placebo
Subjects will be randomized to receive either PTI-808 co-administered with PTI-801 and PTI-428 or placebos once-a-day for 7 days immediately followed by PTI-808 co-administered with PTI-801 or placebos once-a-day for 7 days. A follow-up visit will occur on Day 21.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and tolerability measured by the number of subjects who experience adverse events and potentially significant clinical laboratory assessments, electrocardiography, physical examinations, vital signs.
时间窗: Baseline through Day 21
次要结局
- Apparent terminal half-life (t1/2) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)(Day 1 through 15)
- Time to reach maximum plasma concentration (Tmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)(Day 1 through 15)
- Maximum plasma concentration (Cmax) of multiple oral doses of PTI-808 + PTI-801 and PTI-428 (cohorts 3 & 4 only)(Day 1 through 15)
- Change in FEV1 over time(Baseline through Day 21)