A PHASE 1, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY FOLLOWING SINGLE AND MULTIPLE DOSES OF SISUNATOVIR IN CHINESE HEALTHY 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
- 3
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 1
研究概览
简要总结
The purpose of the study is to learn about:
- The activity of sisunotavir in the body over a period. It includes the processes by which sisunotavir is absorbed, distributed in the body, localized in the tissues, and removed from the body.
- safety and tolerability of sisunatovir (PF-07923568) in Chinese healthy adult participants.
This information is being collected to support further clinical development as well as medicine registration in China.
This study is seeking for participants who:
- are male and female participants aged 18 to 65 years of age.
- are male and female participants who are healthy as seen by medical tests.
- have body mass index (BMI) of 19 to 27 kg/m2 and a total body weight of more than 50 kilograms (110 pounds).
About 12 participants will receive sisunatovir. Four capsules (strength=50 milligrams, 200 milligrams in total) of Sisunatovir will be given on Day 1 on empty stomach. This will be followed by 8 capsules of sisunatovir with 12 hours gap in between four capsules from Days 4 to 7. The participants will have to take 4 capsules of sisunatovir in the morning of 8th day with a meal.
The total time of participants will be in the study is about 71 days. This includes the screening visit to the Follow-up contact. In screening visit, participants will be tested to see if they are fit to take part in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Chinese male and female participants aged 18 to 65 years of age, inclusive, at the time of signing of the informed consent document (ICD).
- •Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, standard 12-lead ECG, and laboratory tests.
- •Body mass index (BMI) of 19 to 27 kg/m2; and a total body weight >50 kg (110 lb).
排除标准
- •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 or situations related to coronavirus disease 2019 (COVID-19) pandemic that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- •Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention with the exception of moderate/strong cytochrome P4503A (CYP3A) inducers or time-dependent inhibitors which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
- •A positive urine drug test, confirmed by a repeat test, if deemed necessary.
- •Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), 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.
- •Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTc corrected using Fridericia's formula [QTcF] >450 ms, complete left bundle branch block [LBBB], signs of an acute or indeterminate- age myocardial infarction, ST-segment and T-wave [ST-T] interval changes suggestive of myocardial ischemia, second- or thirddegree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is >450 ms, this interval should be rate-corrected using the Fridericia method only and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 ms, or quantitative restrictions (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, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:
- •Glomerular filtration rate (GFR) <60 mL/min/1.73m2 based on chronic kidney disease epidemiology (CKD-EPI equation);
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.05 × upper limit of normal (ULN);
- •Gamma-glutamyl transferase (GGT) > 1.05 × ULN;
- •Alkaline phosphatase > 1.05 × ULN;
- •Total bilirubin level ≥1.05 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
研究组 & 干预措施
Arm 1
This only arm will be given as a single dose on Day 1 in a fasted state followed by repeated twice daily doses (200 mg BID, Q12 hours) from Days 4-7 plus 1 morning dose on Day 8 in a fed state
干预措施: Sisunatovir (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 1
时间窗: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1
Cmax was defined as maximum observed plasma concentration. Cmax was observed directly from data.
Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 4
时间窗: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4
Cmax was defined as maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 8
时间窗: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day 8
Cmax was defined as maximum observed plasma concentration.
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 1
时间窗: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day1
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 4
时间窗: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 8
时间窗: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 8
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Sisunatovir on Day1
时间窗: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1
AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day1
时间窗: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1
AUCinf was defined as area under the concentration-time curve from time 0 to infinity.
次要结局
- Time to Reach Cmax (Tmax) on Day 1, Day 4 and Day 8(0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1, and Day 8. 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4.)
- Terminal Elimination Half-life (t½) on Day 1 and Day 8(0, 1, 2, 3, 4, 5, 6, 8, 10, 12,14, 24, 48, 72 hours post dose on Day1, and Day 8)
- Accumulation Ratio for Sisunatovir (Rac)(0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4 and Day 8)
- Accumulation Ratio on Cmax for Sisunatovir (Rac, Cmax)(0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4 and 0, 1, 2, 3, 4, 5, 6, 8, 10, 12,14, 24, 48, 72 hours post dose on Day 8)
- Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs)(From the first dose (Day 1) up to 35 days after the last dose (Day 8) of study intervention (up to 43 days))
- Number of Participants With Vital Signs Meeting the Pre-specified Criteria(Baseline up to Day 11 (11 days))
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)(Baseline up to Day 11 (11 days))
- Number of Participants With Electrocardiogram (ECG) Abnormalities(Baseline up to Day 11 (11 days))