A PHASE 1, OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF ORALLY ADMINISTERED NIRMATRELVIR/RITONAVIR IN PREGNANT WOMEN WITH MILD-TO-MODERATE COVID-19
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 25
- 试验地点
- 24
- 主要终点
- Apparent Oral Clearance (CL/F)
研究概览
简要总结
The purpose of this clinical trial is to learn about how study medicine (Paxlovid, which contains nirmatrelvir and ritonavir) is changed and eliminated from the body, as well as its safety, and the extent to which side effects can be tolerated for treatment of pregnant women with mild or moderate COVID-19 compared to non-pregnant women with mild or moderate COVID-19.
This study is seeking participants who:
- are expecting a healthy baby and are in their second or third trimester pregnancy and have mild or moderate COVID-19
- are not pregnant and have mild or moderate COVID-19.
All participants in this study will take Paxlovid by mouth every 12 hours for 5 days. We will study the experiences of people receiving the study medicine. This will help us decide if the study medicine is safe.
All participants will take part in this study for at least 34 days; pregnant participants will take part until their delivery, so that the study duration may be up to 6 months, depending on their delivery date.
During this time, participants will have 7to 8 visits and, if pregnant, a visit at delivery. Around 2 to 3 visits and the delivery visit will be done in person (at the clinic or at the participant's home). The other 5 visits may be done over the phone, unless in-person visit is necessary as decided by the doctor. Blood samples will be collected on the first 4 to 5 study visits (and at other study visits, if necessary).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
(Open Label)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •All cohorts: Mild-to-moderate COVID-19 infection confirmed in sample collected ≤5 days prior to enrollment; onset within 5 days prior to enrollment and presence of ≥1 sign/symptom on the day of enrollment.
- •Cohorts 1&2: Expecting single baby; Pregnant in 2nd trimester, 14 0/7 to 27 6/7 weeks of gestational age (Cohort 1) or 3rd trimester, ≥28 0/7 and ≤34 6/7 weeks of gestational age (Cohort 2), by ultrasound.
- •All cohorts: Otherwise healthy participants who are determined by medical history, physical examination, and clinical judgment to be appropriate for inclusion in the study
排除标准
- •All cohorts: Current need for hospitalization or anticipated need for hospitalization in the clinical opinion of the site investigator.
- •Cohorts 1&2: Prior/current major condition or illness of mother/fetus substantially increasing risk of study participation/completion or impacting pregnancy/fetal outcomes in investigator's judgement.
- •All cohorts: Current use of any medications that are highly dependent on CYP3A4 for clearance, and which are contraindicated in combination with nirmatrelvir/ritonavir.
- •All cohorts: Has received or is expected to receive monoclonal antibody treatment, convalescent COVID-19 plasma, or anti-viral treatment (eg, molnupiravir) for the current SARSCoV-2 infection.
- •All cohorts: Participants with moderate to severe kidney impairment
研究组 & 干预措施
Cohort 2
Pregnant women in their third trimester
干预措施: nirmatrelvir (Drug)
Cohort 1
Pregnant women in their second trimester
干预措施: nirmatrelvir (Drug)
Cohort 3
Non-pregnant women
干预措施: nirmatrelvir (Drug)
Cohort 3
Non-pregnant women
干预措施: ritonavir (Drug)
Cohort 2
Pregnant women in their third trimester
干预措施: ritonavir (Drug)
Cohort 1
Pregnant women in their second trimester
干预措施: ritonavir (Drug)
结局指标
主要结局
Apparent Oral Clearance (CL/F)
时间窗: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
Apparent Volume of Distribution (Vz/F)
时间窗: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
Maximum Observed Plasma Concentration (Cmax)
时间窗: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
时间窗: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
Incidence of TEAEs, SAEs, and AEs leading to discontinuations
时间窗: Baseline up through end of treatment (Day 5/Day 6)
Plasma Decay Half-Life (t1/2)
时间窗: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
Observed Plasma Trough Concentration (Ctrough)
时间窗: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
Incidence of Treatment Emergent Adverse Events (TEAEs)
时间窗: Baseline up through Day 34
次要结局
- Number of participants with delivery at other location(At delivery of the baby)
- Number of participants with complications during delivery(At delivery of the baby)
- Number of full-term live deliveries(At delivery of the baby)
- Number of premature live deliveries(At delivery of the baby)
- Number of aborted or stillborn fetuses with abnormal findings upon gross visual inspection(At delivery of the baby)
- Incidence of SAEs in newborn infants(Birth through 24 hours after birth or until Study Day 34 (whichever is later))
- Number of participants with caesarean section delivery(At delivery of the baby)
- Number of participants with spontaneous abortions(At delivery of the baby)
- Number of neonates with congenital malformation/anomaly or other neonatal problem(At birth)
- Number of participants with delivery at medical facility(At delivery of the baby)
- Number of participants with delivery at home(At delivery of the baby)
- Gestational age of newborn infants(At birth)
- Body weight of newborn infants(At birth)
- Body length of newborn infants(At birth)
- Head circumference of newborn infants(At birth)
- Number of participants with vaginal delivery(At delivery of the baby)
- Number of participants with induced/elective abortions(At delivery of the baby)
- Number of participants with unknown delivery(At delivery of the baby)
- Number of participants with stillbirths(At delivery of the baby)