Phase I, Open-label, Single-sequence, Cross-over Study of the Effect of Multiple Doses of Itraconazole on Single-dose Tepotinib Pharmacokinetics in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib
研究概览
简要总结
The purpose of this study was to assess the effect of multiple doses of itraconazole on single dose tepotinib pharmacokinetics in healthy participants. Study details include:
Study Duration: up to 48 days Treatment Duration: single dose of tepotinib on Days 1 and 12, 11 days of treatment with itraconazole (Days 8 to 18) Visit Frequency: residence in the Clinical Research Unit from Days -1 to 4 and Days 11 to 15, ambulatory daily visits from Days 5 to 10 and 16 to 20
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Overtly healthy participants as determined by medical evaluation, including no clinically significant abnormality identified by medical history, cardiac monitoring, physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion at Screening and Day -1
- •Had a body weight within 50 and 100 kilogram (inclusive) and Body Mass Index (BMI) within the range greater than or equal (>=) 18.5 and less than or equal to (<=) 29.9 kilogram per meter square (inclusive) at Screening
- •Male or female (not a Women of childbearing potential [WOCBP]). The Investigator confirms that each participant agrees to use appropriate contraception and barriers, if applicable. The contraception, barrier, and pregnancy testing requirements are below:
- •Contraceptive use will be consistent with local regulations on contraception methods for those participating in clinical studies. Male Participants: Agree to the following during the study intervention period and for at least 1 week after the last dose of study intervention: Refrain from donating fresh and unwashed sperm PLUS, either: Abstain from intercourse with a WOCBP.OR Use a male condom: When having sexual intercourse with a WOCBP, who is not currently pregnant, and instruct her to use a highly effective contraceptive method with a failure rate of < 1percent (%) per year
- •Not a WOCBP, confirmed at Screening, by fulfilling at least 1 of the following criteria: Females who are postmenopausal and documentation of irreversible surgical sterilization by hysterectomy, or bilateral oophorectomy, or bilateral salpingectomy
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and this protocol
- •All values for hematology, coagulation, and biochemistry tests of blood and urinalysis within the normal range (at Screening and Day -1)
- •Other protocol defined inclusion criteria could apply
排除标准
- •History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
- •Participants with gall bladder removal or other relevant surgery of gastrointestinal tract (appendectomy is not considered as relevant)
- •History of any malignancy except for adequately treated superficial basal cell carcinoma
- •History of epilepsy
- •Ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or excipients; history of anaphylaxis to drugs or serious allergic reactions leading to hospitalization or any other allergy reaction in general, which the Investigator considers may affect the safety of the participant and/or outcome of the study
- •Any condition, including findings in the laboratory tests, medical history, or other Screening assessments, that in the opinion of the Investigator constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study's objectives, conduct, or evaluation
- •Use of any prescribed medicine or over-the-counter drug or dietary supplement, including herbal remedies, vitamins, and minerals, antacids and dietary supplements such as fish oils within 2 weeks or 5 times the half-life of the respective drug, whichever is longer, prior to the first administration of study intervention
- •Participation in the treatment phase of a clinical study within 60 days or 5 half-lives after last dosing of the previous study drug, whatever is longer, before administration of study drug
- •Contraindication to itraconazole: ventricular dysfunction such as congestive heart failure or a history of congestive heart failure, drug interactions (example: co-administration of a number of CYP3A4 substrates), pregnancy, hypersensitivity to itraconazole
- •Donation or loss of more than 450 milliliter (mL) of blood in the 60 days prior to Screening, donation of plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening
- •Consumption of alcohol from 48 hours prior to first administration of study intervention
- •Smoker (cigarettes, pipes, cigars, or others) or former smoker who stopped smoking for less than 6 months before the time of the Screening visit
- •Inability to communicate or cooperate with the Investigator (example: language problem, illiteracy, poor mental status) or to comply with the requirements of the entire study, including dietary restrictions
- •Other factors, which in the opinion of the Investigator may interfere with study conduct
- •Legal incapacity or limited legal capacity
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Tepotinib then Itraconazole
Participants received a single oral dose of Tepotinib 500 milligrams (mg) on Day and Day 12 under fed condition followed by single oral dose of itraconazole 200 mg on Days 8 to 11 and Days 13 to 18. On Day 12, participants received a single dose of 200 mg itraconazole simultaneously with a single dose of 500 mg Tepotinib.
干预措施: Tepotinib (HydroChloride hydrate) (Drug)
Tepotinib then Itraconazole
Participants received a single oral dose of Tepotinib 500 milligrams (mg) on Day and Day 12 under fed condition followed by single oral dose of itraconazole 200 mg on Days 8 to 11 and Days 13 to 18. On Day 12, participants received a single dose of 200 mg itraconazole simultaneously with a single dose of 500 mg Tepotinib.
干预措施: Itraconazole (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib
时间窗: Predose up to 168 hours post dose
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda (λ)z determination.
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Measurable Concentration (AUC0-tlast) of Tepotinib
时间窗: Predose up to 168 hours post dose
The AUC from time zero (= dosing time) to time of the last quantifiable concentration (tlast). Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Metabolite
时间窗: Predose up to 168 hours post dose
Cmax was obtained directly from the concentration versus time curve.
次要结局
- Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib(Predose up to 168 hours post dose)
- Apparent Volume of Distribution (Vz/f) for Tepotinib(Predose up to 168 hours post dose)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAES With Severity of Grade Greater or Equal to 3(Baseline (Day 1) up to follow up (assessed up to Day 20))
- Number of Participants With Clinically Meaningful Change From Baseline in Vital Signs(Baseline (Day 1) up to follow up (assessed up to Day 20))
- Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib(Predose up to 168 hours post dose)
- Number of Participants With Clinically Meaningful Change From Baseline in Laboratory Values(Baseline (Day 1) up to follow up (assessed up to Day 20))
- Number of Participants With Clinically Meaningful Change From Baseline in Electrocardiogram (ECG)(Baseline (Day 1) up to follow up (assessed up to Day 20))
- Apparent Terminal Half-Life (t1/2) of Tepotinib in Plasma(Predose up to 168 hours post dose)