A PHASE 1, OPEN-LABEL, FIXED SEQUENCE STUDY TO ESTIMATE THE EFFECT OF CARBAMAZEPINE ON THE PHARMACOKINETICS OF IBUZATRELVIR IN HEALTHY ADULT PARTICIPANTS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of ibuzatrelvir
研究概览
简要总结
The purpose of this study is to estimate the effect of carbamazepine, a strong CYP3A4 inducer, on the pharmacokinetics (PK) of ibuzatrelvir in healthy participants.
This study is seeking participants who:
- are male or female that are not of childbearing potential of 18 years of age or older
- are examined to be healthy
The study will consist of two treatments: (1) a single oral dose of ibuzatrelvir 600 mg alone in Period 1 and (2) carbamazepine q12h (BID) titrated from 100 mg to 300 mg over 15 days with a single ibuzatrelvir 600 mg dose coadministered on day 15 in Period 2. All treatments will be taken by mouth.
All participants will remain in the study clinic for 18 days for safety review, laboratory collections, and to collect samples for PK.
All participants selected in the study will be required to go through a screening period up to 28 days. A screening period is the time during which a few participants are examined to see whether they are fit for the study. During this period, the participant's medical history and past and current medications will be reviewed. A series of tests will also be performed to see if they are good to be selected for the study. If the participant meets all required criteria and are interested in continuing, the participant will be brought into the study clinic to stay overnight for 18 days. About 28 to 35 days after discharge following the final treatment, the participant will be contacted for a follow up visit either in person or by telephone. This is to check up on how the participant is doing and to conclude the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Male participants and female participants who are not of childbearing potential who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, blood pressure, pulse rate and standard 12 lead ECG
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- •Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- •Subjects shown to carry or be positive for HLA-B*1502 or HLA-A*3101 (genotyping alleles/markers related to carbamazepine-associated hypersensitivity reactions, including SJS/TEN).
- •Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants <60 years; and ≥150/90 mm/Hg for participants ≥60 years old, following at least 5 minutes of supine rest. If systolic BP is ≥ 140 or 150 mm Hg (based on age) or diastolic ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
- •An eGFR <60 mL/min/1.73m², as determined by the CKD-EPI equation using Screat calculated using the recommended formulas
- •Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >450 ms, complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.
- •Participants with ANY of the following abnormalities in clinical laboratory tests at screening and prior to dosing in each period, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: ALT, AST, Bilirubin ≥1.5 x ULN. Participants with an elevated total bilirubin consistent with Gilberts Disease may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
研究组 & 干预措施
Period 1
ibuzatrelvir single oral dose on Day 1.
干预措施: ibuzatrelvir (Drug)
Period 2
carbamazepine BID oral doses on Day 1-15. ibuzatrelvir single oral dose on Day 14.
干预措施: ibuzatrelvir (Drug)
Period 2
carbamazepine BID oral doses on Day 1-15. ibuzatrelvir single oral dose on Day 14.
干预措施: carbamazepine ER (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of ibuzatrelvir
时间窗: Hour 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 post-dose in each period
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of ibuzatrelvir
时间窗: Hour 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 post-dose in each period
if data permits
Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) ofibuzatrelvir
时间窗: Hour 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 post-dose in each period
次要结局
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs(Baseline up to Day 18)
- Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)(Baseline (Day 0) up to 35 days after last dose of study medication)
- Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities(Baseline up to Day 18)