A Phase 1, Open-Label Study to Evaluate Pharmacokinetics and Drug-drug Interactions of ENV-101 in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 57
- 试验地点
- 2
- 主要终点
- Cohort 3: Time of pirfenidone maximum blood concentration (Tmax) after administration alone and after coadministration with taladegib
研究概览
简要总结
The purposes of this study are to:
- evaluate potential interactions between taladegib (ENV-101) and current standard-of-care (SOC) therapies for idiopathic pulmonary fibrosis (IPF), including nintedanib and pirfenidone, and
- more fully characterize the pharmacokinetics (PK) of taladegib (i.e., how the body absorbs, distributes, metabolizes and excretes taladegib).
This study will enroll 4 cohorts (groups) of participants. Each cohort will experience a different duration of treatment and sequestering (being housed) at the clinical site, followed by a 14-day follow-up period for safety evaluation. The longest duration of treatment for any cohort is 30 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 26 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants are reproductively sterile.
- •Body Mass Index (BMI) ≥ 18.5 and ≤ 32 kg/m2 and body weight ≥ 50 kg at study start.
- •Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or electrocardiograms (ECGs) prior to dosing, as deemed by the Investigator.
- •Able to swallow multiple capsules and tablets.
- •Participants are willing to remain on study treatment for the duration of the study and comply with all study days and procedures.
- •Participants willing to sign and have a full understanding of the informed consent.
- •Participants must be willing to be sequestered for the time period indicated for their respective cohort.
排除标准
- •Chronic or current use of any prescription or over the counter medications; or acute use of prescription medications within 14 days or 5 half-lives, whichever is longer, or over the counter medications within 7 days or 5 half-lives, whichever is longer, prior to study start, or planned use during all study periods.
- •Participant is unwilling to refrain from fruits (including juices) that inhibit CYP3A4, including grapefruit, Seville orange, pomelo, or star fruit, beginning 7 days prior to study start through end of study.
- •Active infection with hepatitis B or C, or human immunodeficiency virus (HIV) during screening.
- •Current alcohol or drug abuse.
- •Smoking or other nicotine use (including but not limited to vaping, nicotine patch, nicotine gum or nicotine lozenge) within 3 months prior to screening, current smoker, or unwillingness to refrain from smoking for the duration of the study.
- •History or presence (per participant history) of:
- •Autoimmune disease such as rheumatoid arthritis or systemic lupus erythematosus
- •Thrombophlebitis or deep vein thrombosis
- •Hematologic or coagulation disorders
- •Liver disease or dysfunction; Gilbert's syndrome
- •Renal dysfunction or glomerulonephritis
- •Coronary artery disease
- •Diverticular disease
- •Congestive heart failure or ventricular dysfunction
- •Clinically significant cardiovascular, gastrointestinal, pulmonary, endocrine, central nervous system disorders, or other major active and uncontrolled disease in the opinion of the Investigator.
- •History of malignancy of any type, other than in situ cervical cancer or surgically excised non-melanomatous skin cancers, within 5 years before study start.
- •Participation in a clinical research trial that included the receipt of an investigational agent or any experimental procedure within 30 days or 5 half-lives, whichever is longer, prior to screening, during screening, or planned participation in any such trial while participating in this study.
- •Major surgery requiring hospitalization (according to the Investigator) performed within 3 months prior to screening, or planned during the course of the trial.
- •Participants with clinically significant cardiac abnormalities including but not limited to: has pacemaker; or is not in sinus rhythm during screening; or has a left bundle branch block or bifascicular block during screening; or any prior history of ventricular arrhythmia or torsades de pointes.
- •Participant is unwilling to adhere to the on-study diet provided by the clinical site during study participation.
- •Females who are pregnant or nursing.
- •Participants that are unwilling to refrain from blood or blood product donation for the duration of the study and for 30 days after their final dose of any study treatment.
- •Males who are unwilling to refrain from sperm donation for the duration of the study and for 95 days after their final dose of any study treatment.
- •Females who are unwilling to refrain from egg donation for the duration of the study and for 95 days after their final dose of any study treatment.
- •Participants with a history of a severe allergic reaction or anaphylactic reaction or known hypersensitivity to any component of taladegib (all cohorts), nintedanib (Cohort 1), or pirfenidone (Cohorts 2 and 3).
- •Participants who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study investigative site or the study Sponsor.
研究组 & 干预措施
Cohort 2 (effect of pirfenidone on taladegib pharmacokinetics)
This cohort will receive multiple days of pirfenidone three times a day to see its effect on a single dose of taladegib.
干预措施: pirfenidone (Drug)
Cohort 4 (measure taladegib pharmacokinetics)
This cohort will receive a single dose of taladegib to measure its pharmacokinetic profile.
干预措施: taladegib (Drug)
Cohort 1 (effect of nintedanib on taladegib pharmacokinetics)
This cohort will receive multiple days of nintedanib twice a day to see its effect on a single dose of taladegib.
干预措施: taladegib (Drug)
Cohort 1 (effect of nintedanib on taladegib pharmacokinetics)
This cohort will receive multiple days of nintedanib twice a day to see its effect on a single dose of taladegib.
干预措施: nintedanib (Drug)
Cohort 2 (effect of pirfenidone on taladegib pharmacokinetics)
This cohort will receive multiple days of pirfenidone three times a day to see its effect on a single dose of taladegib.
干预措施: taladegib (Drug)
Cohort 3 (effect of taladegib on pirfenidone pharmacokinetics)
This cohort will receive multiple days of taladegib once a day to see its effect on a single dose of pirfenidone.
干预措施: taladegib (Drug)
Cohort 3 (effect of taladegib on pirfenidone pharmacokinetics)
This cohort will receive multiple days of taladegib once a day to see its effect on a single dose of pirfenidone.
干预措施: pirfenidone (Drug)
结局指标
主要结局
Cohort 3: Time of pirfenidone maximum blood concentration (Tmax) after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 4: Apparent oral clearance (CL/F) of taladegib after administration alone
时间窗: Day 1
Cohort 2: Elimination rate constant (K[el]) for taladegib after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 4: Apparent volume of distribution (Vz/F) of taladegib after administration alone
时间窗: Day 1
Cohort 2: Apparent oral clearance (CL/F) of taladegib after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 4: Taladegib extrapolated total absorption (AUC[extrapolated]) after administration alone
时间窗: Day 1
Cohort 1: Taladegib (ENV-101) maximum blood concentration (Cmax) after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
Cohort 1: Time of taladegib maximum blood concentration (Tmax) after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
Cohort 4: Taladegib half-life in the blood (T1/2) after administration alone
时间窗: Day 1
Cohort 4: Elimination rate constant (K[el]) for taladegib after administration alone
时间窗: Day 1
Cohort 3: Pirfenidone absorption to time t (AUC[0-t]) after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 2: Apparent volume of distribution (Vz/F) of taladegib after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 3: Pirfenidone maximum blood concentration (Cmax) after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 1: Taladegib absorption to time t (AUC[0-t]) after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
AUC\[0-t\] represents "area under the concentration-time curve" and measures the amount of drug that is present in the blood from the time of administration to a given time t
Cohort 1: Taladegib total absorption (AUC[0-infinity]) after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
Cohort 1: Taladegib extrapolated total absorption (AUC[extrapolated]) after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
Cohort 1: Taladegib half-life in the blood (T1/2) after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
Cohort 1: Elimination rate constant (K[el]) for taladegib after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
K\[el\] represents the fraction of a drug that is removed from the body per unit of time.
Cohort 1: Apparent oral clearance (CL/F) of taladegib after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
Apparent oral clearance represents the volume of plasma cleared of drug per unit time after oral administration.
Cohort 1: Apparent volume of distribution (Vz/F) of taladegib after administration alone and after coadministration with nintedanib
时间窗: Day 1 and Day 13
Apparent volume of distribution signifies how extensively a drug distributes throughout the body, accounting for bioavailability.
Cohort 2: Taladegib maximum blood concentration (Cmax) after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 2: Time of taladegib maximum blood concentration (Tmax) after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 2: Taladegib absorption to time t (AUC[0-t]) after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 2: Taladegib total absorption (AUC[0-infinity]) after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 2: Taladegib extrapolated total absorption (AUC[extrapolated]) after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 2: Taladegib half-life in the blood (T1/2) after administration alone and after coadministration with pirfenidone
时间窗: Day 1 and Day 27
Cohort 3: Pirfenidone total absorption (AUC[0-infinity]) after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 3: Pirfenidone extrapolated total absorption (AUC[extrapolated]) after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 3: Pirfenidone half-life in the blood (T1/2) after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 3: Elimination rate constant (K[el]) for pirfenidone after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 3: Apparent oral clearance (CL/F) of pirfenidone after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 3: Apparent volume of distribution (Vz/F) of pirfenidone after administration alone and after coadministration with taladegib
时间窗: Day 1 and Day 6
Cohort 4: Taladegib maximum blood concentration (Cmax) after administration alone
时间窗: Day 1
Cohort 4: Time of taladegib maximum blood concentration (Tmax) after administration alone
时间窗: Day 1
Cohort 4: Taladegib absorption to time t (AUC[0-t]) after administration alone
时间窗: Day 1
Cohort 4: Taladegib total absorption (AUC[0-infinity]) after administration alone
时间窗: Day 1
次要结局
未报告次要终点