COVID-19: A PHASE 1, OPEN-LABEL, 3-TREATMENT, 6-SEQUENCE, 3-PERIOD CROSSOVER STUDY TO ESTIMATE THE EFFECT OF PF-07321332/RITONAVIR AND RITONAVIR ON THE PHARMACOKINETICS OF MIDAZOLAM IN 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
- 1
- 主要终点
- Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Midazolam When Administered Alone and With PF-07321332/Ritonavir
研究概览
简要总结
The purpose of this study is to estimate the effect PF-07321332/Ritonavir and Ritonavir on Midazolam (a cytochrome P450 [CYP]3A4 substrate) in Healthy Adult Participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Female participants of childbearing potential must have a negative (urine or serum) pregnancy test.
- •Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
排除标准
- •Positive test result for SARS-CoV-2 infection at the time of Screening or Day -
- •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).
- •Clinically relevant abnormalities requiring treatment (eg, acute myocardial infarction, unstable ischemic conditions, evidence of ventricular dysfunction, serious tachy or brady arrhythmias) or indicating serious underlying heart disease (eg, prolonged PR interval, cardiomyopathy, heart failure greater than New York Heart Association (NYHA) 1, underlying structural heart disease, Wolff Parkinson-White syndrome).
- •Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
- •History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or hepatitis C virus (HCVAb). Hepatitis B vaccination is allowed.
- •Other 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 COVID-19 pandemic (eg, Contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
研究组 & 干预措施
Treatment B
PF-07321332/ritonavir orally + Midazolam orally
干预措施: PF-07321332/ritonavir + Midazolam (Drug)
Treatment A
Midazolam orally
干预措施: Midazolam (Drug)
Treatment C
Ritonavir orally + Midazolam orally
干预措施: Ritonavir + Midazolam (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Midazolam When Administered Alone and With PF-07321332/Ritonavir
时间窗: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose
AUClast for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \[test\]/midazolam \[reference\] and 90% CIs) were expressed as percentages.
Maximum Plasma Concentration (Cmax) of Midazolam When Administered Alone and With PF-07321332/Ritonavir
时间窗: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose
Cmax for midazolam following single dose administration with and without PF-07321332/ritonavir was observed directly from data. Natural log-transformed Cmax for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \[test\]/midazolam \[reference\] and 90% CIs) were expressed as percentages.
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinity Time (AUCinf) of Midazolam When Administered Alone and With PF-07321332/Ritonavir
时间窗: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose
AUCinf for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. Natural log-transformed AUCinf for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \[test\]/midazolam \[reference\] and 90% CIs) were expressed as percentages.
次要结局
- Number of Participants With Vital Signs Abnormalities(Baseline up to Day 28)
- Time for Cmax (Tmax) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir(Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Number of Participants With Laboratory Abnormalities(Baseline up to Day 28)
- Cmax of Midazolam When Administered Alone and With Ritonavir(Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- AUCinf of Midazolam When Administered Alone and With Ritonavir(Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Baseline up to Day 28)
- Number of Participants With Electrocardiogram (ECG) Abnormalities(Baseline up to Day 28)
- AUClast of Midazolam When Administered Alone and With Ritonavir(Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose)
- Apparent Volume of Distribution (Vz/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir(Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Apparent Clearance (CL/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir(Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)
- Terminal Half-life (t1/2) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir(Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose)