A PHASE I, MULTIPLE DOSE, OPEN-LABEL PHARMACOKINETIC STUDY OF NIRMATRELVIR/RITONAVIR IN HEALTHY LACTATING WOMEN
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- The Maximum Observed Concentration of Nirmatrelvir in Breast Milk Over the Dosing Interval
研究概览
简要总结
The main purpose of this study is to measure the level of active ingredient of the study medicine (nirmatrelvir) that is secreted in human breast milk when it is given to healthy breastfeeding women. The study medicine consists of two medicines, nirmatrelvir and ritonavir. We are seeking female participants who are:
- Actively breast-feeding (lactating) at least 12 weeks postpartum;
- Age between 18 to 55 years and not currently pregnant;
- Have a Body Mass Index (BMI): 17.5 kg/m2; and a total body weight >50 kg (110 lb).
Participants will take the study medicine by mouth for a total of 3 times over 2 days (2 morning doses and 1 evening dose) at the study clinic. We will periodically collect breast milk from day 2 to 4 to measure the level of nirmatrelvir and ritonavir in it. A safety follow up call will be conducted around 28-35 days from the last dose to monitor any reactions participants may have to the study medicine.
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 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy lactating females who are actively breast-feeding or expressing breast milk, at least 12 weeks post-partum and not currently pregnant between 18 and 55 years old
- •Body Mass Index (BMI): 17.5 kg/m2; and a total body weight >50 kg (110 lb)
- •Infants of women enrolled in the study must be able to feed successfully from a bottle or other age-appropriate alternative feeding method prior to the start of the study and must be able to tolerate infant formula if the mother does not have a supply of stored breast milk sufficient to cover the duration of the study
- •Participants must be willing to temporarily discontinue breast feeding their infants for a total of 4.5 days (108 hours)
- •Participants must be willing to regularly pump breasts throughout the study and express milk according to a schedule designed to maintain lactation throughout the study period
排除标准
- •Positive test result (RT-PCR) for SARS-CoV-2 infection at the time of screening or Day -1
- •Evidence or history of clinically significant findings
- •History of febrile illness or mastitis within 5 days prior to the first dose of study medication
- •Participants who have received a COVID-19 vaccine within 7 days before screening or admission, or who are to be vaccinated with a COVID-19 vaccine at any time during the study confinement period
- •History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed
- •Abnormal vital signs such as blood pressure, 12-lead electrocardiogram
- •History of alcohol abuse and/or illicit drug use, tobacco use in excess of 5 cigarettes/day or 2 chews/day
- •Blood donation within 60 days
研究组 & 干预措施
nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will be given by mouth two times a day as a tablet
干预措施: nirmatrelvir (Drug)
nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will be given by mouth two times a day as a tablet
干预措施: ritonavir (Drug)
结局指标
主要结局
The Maximum Observed Concentration of Nirmatrelvir in Breast Milk Over the Dosing Interval
时间窗: At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2
The maximum observed concentration and was directly observed from data.
Time to Reach Cmax of Nirmatrelvir in Breast Milk
时间窗: At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2
Cmax was defined as maximum observed concentration of nirmatrelvir in breast milk.
Area Under the Concentration-Time Profile From Time Zero to End of Dosing Interval for Nirmatrelvir in Breast Milk
时间窗: At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2
Area under the concentration curve for nirmatrelvir in breast milk from time 0 to end of dosing interval.
Terminal Half-Life of Nirmatrelvir in Breast Milk
时间窗: At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2
The time measured for the breast milk nirmatrelvir concentration to decrease by one half.
The Average Steady State Concentration of Nirmatrelvir in Breast Milk
时间窗: At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2
The average concentration across time and can be calculated by dividing AUCtau by time. AUCtau was defined area under the concentration curve from time 0 to end of dosing interval.
The Amount of Nirmatrelvir Excreted in Breast Milk Over the Dosing Interval Tau
时间窗: At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2
The amount of nirmatrelvir excreted into breast milk over the dosing interval.
The Percent of Amount of Nirmatrelvir Excreted in Breast Milk Over The Dosing Interval Tau
时间窗: At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2
The percent of nirmatelvir excreted in breast milk to amount of breast milk over the dosing interval .
Breast Milk Clearance of Nirmatrelvir
时间窗: At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2
Clearance was defined as the apparent volume (Liter) of breast milk completely cleared the nirmatrelvir per hour.
次要结局
- The Maximum Observed Concentration of Ritonavir in Breast Milk Observed Over the Dosing Interval(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Time to Reach Cmax of Ritonavir in Breast Milk(At Day -1 (24 Hours Prior to Dosing on Day 1), 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Area Under the Concentration-Time Profile for Ritonavir in Breast Milk From Time Zero to End of Dosing Interval(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Half-Life of Ritonavir in Breast Milk(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- The Average Steady State Concentration of Ritonavir in Breast Milk(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- The Amount of Ritonavir Excreted in Breast Milk Over the Dosing Interval Tau(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- The Percent of Ritonavir Excreted in Breast Milk Over The Dosing Interval Tau(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Breast Milk Clearance of Ritonavir(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- The Maximum Observed Concentration of Nirmatrelvir in Plasma Observed Over the Dosing Interval(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- The Maximum Observed Concentration of Ritonavir in Plasma Observed Over the Dosing Interval(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Area Under the Concentration-Time Profile for Nirmatrelvir in Plasma From Time Zero to End of Dosing Interval(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Area Under the Concentration-Time Profile for Ritonavir in Plasma From Time Zero to End of Dosing Interval(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Half-Life of Nirmatrelvir in Plasma(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Half-Life of Ritonavir in Plasma(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- The Minimum Plasma Concentration of Nirmatrelvir Observed Over the Dosing Interval(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- The Minimum Plasma Concentration of Ritonavir Observed Over the Dosing Interval(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Time to Reach Cmax of Nirmatrelvir in Plasma(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Time to Reach Cmax of Ritonavir in Plasma(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Apparent Clearance of Nirmatrelvir From Plasma(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Apparent Clearance of Ritonavir From Plasma(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Apparent Volume of Nirmatrelvir Distribution(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Apparent Volume of Ritonavir Distribution(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- The Average Steady State Concentration of Nirmatrelvir in Plasma(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- The Average Steady State Concentration of Ritonavir in Plasma(At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2)
- Daily (24 Hour) Amount of Nirmatrelvir Excreted in Breast Milk(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Daily (24 Hour) Amount of Ritonavir Excreted in Breast Milk(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Milk to Plasma Ratio of Nirmatrelvir for AUCtau During Dosing Interval(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Milk to Plasma Ratio of Ritonavir for AUCtau During Dosing Interval(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Milk to Plasma Ratio of Nirmatrelvir for Cmax During Dosing Interval(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Milk to Plasma Ratio of Ritonavir for Cmax During Dosing Interval(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Body Weight Normalized Infant Dose (BWNID) of Nirmatrelvir in mg/kg/Day(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- BWNID of Ritonavir in mg/kg/Day(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Body Weight Normalized Maternal Dose (BWNMD) of Nirmatrelvir in mg/kg/Day(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- BWNMD of Ritonavir in mg/kg/Day(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Infant Dose Expressed As % of Body Weight Normalized Maternal Dose (BWNIDPCM) for Nirmatrelvir(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- BWNIDPCM for Ritonavir(At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2)
- Number of Participants With Treatment Emergent Adverse Events(From the first dose of study treatment on Day 1 to up to 28 days after the last dose of study intervention on Day 2 (maximum to 30 days))
- Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)(At Screening (Day -28 to Day -2), Day -1, and Day 4)
- Number of Participants With Vital Signs Abnormalities(At Screening (Day -28 to Day -2), Pre-dose and 12 Hours post-dose on Day 1, Pre-dose and 48 Hours Post-dose on Day 2)
- Number of Participants With ECG Abnormalities(At Screening (from Day -28 to Day -2))
- Number of Participants With Physical Examination Abnormalities(At Screening (from Day -28 to Day -2) or Day -1)