NCT04413552已完成1 期
A Phase I, Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of INDV-2000 (C4X_3256) Under Fasting and Fed Conditions in Healthy Volunteers
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This study is a single ascending dose (SAD) study conducted to identify the maximum tolerated dose (MTD) of INDV-2000. After completion of the SAD portion of the study and acceptable safety evaluation, a food-interaction, single-dose study under fed and fasted conditions will be conducted.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Part I: Double-blind;
Part II: Open-label
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Must be able to verbalize understanding the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures, and be able to comply with protocol requirements, rules and regulations of the study site, and be likely to complete all the study interventions.
- •Must be considered a healthy male or non-childbearing female for Part I
- •For Part II, must be a healthy male who did not participate in Part I and willing to consume a high-fat meal.
- •Body mass index (BMI) within 18.0 to 30.0 kg/m^2, inclusive (minimum weight of at least 50.0 kg at Screening)
- •Male subjects who are sexually active with female partners of child-bearing potential must use, with their partner, a condom plus an approved method of effective contraception from time of screening until 90 days after last dose of Investigational Medicinal Product (IMP). Additionally, male subjects must agree to not donate sperm during the study and for at least 90 days from last dose of IMP.
排除标准
- •Have a medical history of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder as judged by an Investigator,
- •Have clinically significant abnormal biochemistry, hematology or urinalysis results as judged by an Investigator,
- •Have a history of narcolepsy or other significant sleep disorders
- •Have disorders that may interfere with drug absorption, distribution, metabolism and excretion (ADME) processes,
- •Positive test results for human immunodeficiency virus (HIV)-1/HIV-2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb).
- •Serious cardiac illness or other medical condition including, but not limited to: Uncontrolled arrhythmias; History of congestive heart failure (CHF); myocardial infarction < 6 months from receipt of first dose of IMP; uncontrolled symptomatic angina; corrected QT value (QTcF) > 450 msec for males and > 470 msec for females or history of prolonged QT syndrome; Have a blood pressure reading outside of the following range: systolic < 86 or > 149 mmHg; diastolic < 50 or > 94 mmHg
- •Current active hepatic or biliary disease. Subjects with cholecystectomy < 90 days prior to screening.
- •Regular alcohol consumption in males > 21 units per week and females > 14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
- •Positive test result for alcohol and/or drugs of abuse at screening or prior to the first IMP administration.
- •Current smokers and those who have smoked within the last 90 days. Current users of e-cigarettes and nicotine replacement products, and those who have used these products within the last 90 days.
- •Concurrent treatment or treatment with an investigational drug within 30 days prior to the first dose.
- •Blood donation of approximately 500 mL within 56 days or plasma donation within 7 days of screening.
- •Subjects who are taking, or have taken, any prescribed or over-the-counter drugs (other than 2 g per day acetaminophen, hormone replacement therapy, hormonal contraception) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis if considered not to interfere with the objectives of the study, as agreed by an Investigator and Sponsor's Medical Monitor.
- •Any consumption of food or drink containing poppy seeds, grapefruit or Seville oranges within 7 days prior to the IMP administration
- •Treatment with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) 3A4 within 30 days prior to first dose of IMP.
- •Known allergy or hypersensitivity to IMP or its excipients.
- •Any condition that, in the opinion of an Investigator, would interfere with evaluation of the IMP or interpretation of subject safety or study results.
- •Affiliated with, or a family member of, site staff directly involved in the study, or anyone with a financial interest in the outcome of the study.
- •Subjects who are unable, in the opinion of an Investigator, to comply fully with the study requirements.
研究组 & 干预措施
Part I: INDV-2000
Experimental
Participants will receive a single dose of INDV-2000. The starting dose is 1 mg with dose escalation dependent upon observed clinical safety, tolerability and pharmacokinetics.
干预措施: INDV-2000 (Drug)
Part I: Placebo
Placebo Comparator
Participants will receive a single dose of matching placebo.
干预措施: Placebo (Drug)
Part II: INDV-2000 Fasted/Fed
Experimental
Participants will receive a single dose of INDV-2000 orally on Day 1 under fasted conditions and a single dose of INDV-2000 after a high-fat breakfast on Day 8. Dose to be determined based on a well-tolerated dose studied in Part I.
干预措施: INDV-2000 (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From first dose of study drug to end of study participation for each cohort; 11 days in Part 1 and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).
An adverse event (AE) was considered related to study drug if it could not reasonably be explained by other factors. A serious AE is any event that met any of the following criteria: * Death * Life-threatening * In-patient hospitalization or prolongation of existing hospitalization * Persistent or significant disability/incapacity * Congenital anomaly/birth defect * Other important medical event that may have jeopardized the participant or required an intervention to prevent an above outcome. A severe AE describes the intensity of an AE, defined as causing marked limitation in activity; medical intervention or therapy or hospitalization required. For vital sign and laboratory abnormalities assessed as AEs, intensity was graded in accordance with the Food and Drug Administration Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, where Grade 3 = serious and Grade 4 = potentially life-threatening.
次要结局
- Number of Participants With Clinically Significant Laboratory Findings(From first dose of study drug to end of study participation for each cohort; 11 days in Part I and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).)
- Number of Participants With Clinically Significant Changes in Vital Signs(From first dose of study drug to end of study participation for each cohort; 11 days in Part 1 and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).)
- Part I: Time to Maximum Observed Plasma Concentration (Tmax) of M12 After a Single Dose of INDV-2000(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings(From first dose of study drug to end of study participation for each cohort; 11 days in Part I and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).)
- Number of Participants With Clinically Significant Physical Examination Findings(From first dose of study drug to end of study participation for each cohort; 11 days in Part I and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).)
- Part I: Maximum Observed Plasma Concentration (Cmax) of INDV-2000 After a Single Dose(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of INDV-2000 After A Single Dose(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Apparent Plasma Clearance (CL/F) of INDV-2000 After a Single Dose(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Plasma Terminal Half-life of INDV-2000 After a Single Dose(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Plasma Terminal Half-life of M12 After a Single Dose of INDV-2000(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: Apparent Clearance of INDV-2000 After a Single Dose Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: Plasma Terminal Half-life of INDV-2000 After a Single Dose Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Time to Maximum Observed Plasma Concentration (Tmax) of INDV-2000 After a Single Dose(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC0-last) of INDV-2000 After A Single Dose(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration of M12 After A Single Dose of INDV-2000(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Maximum Observed Plasma Concentration (Cmax) of M12 After a Single Dose of INDV-2000(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part I: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M12 After A Single Dose of INDV-2000(Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: AUC0-inf of INDV-2000 After a Single Dose Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: Cmax of INDV-2000 After a Single Dose Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: Tmax of INDV-2000 After a Single Dose Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: AUC0-last of INDV-2000 After a Single Dose Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: Cmax of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: Tmax of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: AUC0-last of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: AUC0-inf of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
- Part II: Plasma Terminal Half-life of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions(Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose)
研究者
研究点 (1)
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