A Phase 1, Open-label Study to Evaluate Vonoprazan Concentrations in Breast Milk of Healthy Lactating Women Receiving Vonoprazan 20 mg Once Daily or Vonoprazan 20 mg Twice Daily
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Area Under Drug Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Following the Morning Dose of Vonoprazan in Breast Milk
研究概览
简要总结
The primary objective is to determine the pharmacokinetics (PK) of vonoprazan in breast milk of healthy lactating women who have received vonoprazan administered once daily or vonoprazan 20 mg administered twice daily for 4 consecutive days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- Female
- 接受健康志愿者
- 是
入选标准
- •The participant is a healthy lactating woman at least 18 years of age at the time of signing the informed consent form (ICF).
- •The participant has delivered a normal term infant (at least 37 weeks gestation) and has been breastfeeding or actively pumping breast milk for at least 4 weeks postpartum prior to the first dose.
- •The participant is willing to not breastfeed or otherwise use her breast milk during administration of vonoprazan and until at least 5 days after the last dose of the study drug.
- •The participant has confirmed that her breastfed infant is able to feed from a bottle.
- •The participant agrees to collect all breast milk from pre-dose to 24 hours after the morning dose administration on Day 4, using an electric pump.
- •The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at Screening.
- •Participants of childbearing potential must use an acceptable method of birth control (ie, diaphragm with spermicide, intrauterine device, condom with foam or vaginal spermicide, oral contraceptives, or abstinence) or be surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy). All participants must have a negative pregnancy test at Screening and before the first dose of study drug (Baseline).
- •The participant agrees to comply with all protocol requirements.
- •The participant is able to provide written informed consent.
排除标准
- •The participant has a positive pregnancy test at Screening or Baseline, is planning to become pregnant before, during, or within 4 weeks after participating in this study, or intends to donate ova during this time period, or is of childbearing potential and not using an effective contraceptive method.
- •The participant has a history of breast implants, breast augmentation, or breast reduction surgery that significantly impacts breastfeeding or collection of milk from one or both breasts.
- •The participant has signs or symptoms of mastitis or other condition that would prevent the collection of milk from one or both breasts.
- •The participant has undergone prior esophageal and/or gastrointestinal surgeries that may affect study drug absorption.
- •The participant has undergone surgery (other than cesarean section) within 30 days before the first dose of study drug.
- •The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at Screening.
- •The participant has any other clinically significant findings on physical examination, clinical laboratory abnormalities, or ECG results that preclude participation in the study, as deemed by the investigator.
- •The participant has used any prescription (excluding hormonal birth control) and/or over-the-counter medications (including cytochrome P450 3A4 inducers), including herbal or nutritional supplements, within 14 days before the first dose of study drug, and/or is expected to require any such medication during the course of the study until end of the Treatment Period. Use of multivitamins and acetaminophen (up to 2 g per day) is permissible.
- •The participant has consumed grapefruit and/or grapefruit juice, Seville orange, or Seville orange-containing products (eg, marmalade) within 7 days before the first dose of study drug and/or is expected to be unable to abstain through the study.
- •The participant is a smoker or has used nicotine or nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 6 months before the first dose of study drug.
- •The participant has a history of alcohol abuse or drug dependency within 12 months before the first dose of study drug.
- •The participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at Screening, Baseline, or Day 4 (Check-in).
- •The participant is involved in strenuous activity or contact sports within 24 hours before the first dose of study drug and during the study.
- •The participant has a history of relevant drug and/or food allergies (ie, any significant food allergy that could preclude a standard diet in the clinical research unit).
- •The participant has received study drug in another investigational study (including vonoprazan) within 30 days prior to start of the Screening Period.
- •The participant has a history of hypersensitivity or allergies to vonoprazan or any of its formulation excipients (D-mannitol, microcrystalline cellulose, hydroxypropyl cellulose, fumaric acid, ascorbic acid, croscarmellose sodium, magnesium stearate, hypromellose, polyethylene glycol 8000, titanium dioxide, or ferric oxide red).
- •In the opinion of the investigator, the participant is not suitable for entry into the study.
研究组 & 干预措施
Vonoprazan 20 mg Once Daily
Participants will be administered once-daily doses of vonoprazan 20 mg for 4 consecutive days (Days 1 through 4).
干预措施: Vonoprazan (Drug)
Vonoprazan 20 mg Twice Daily
Participants will be administered twice-daily doses of vonoprazan 20 mg for 4 consecutive days (Days 1 through 4).
干预措施: Vonoprazan (Drug)
结局指标
主要结局
Area Under Drug Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Following the Morning Dose of Vonoprazan in Breast Milk
时间窗: Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).
AUC from time 0 to 24 hours post-dose, calculated as: the sum of the product of the concentration of the interval and the width of the interval.
Maximum Drug Concentration (Cmax) of Vonoprazan in Breast Milk
时间窗: Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).
Maximum observed concentration after dosing.
Minimum Drug Concentration (Cmin) of Vonoprazan in Breast Milk
时间窗: Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).
Minimum observed concentration after dosing.
Average Drug Concentration (Cavg) of Vonoprazan in Breast Milk
时间窗: Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).
Average concentration, calculated as: AUC0-24/tau (tau=the difference between the end time of the last interval and dosing time).
Time to Cmax (Tmax) of Vonoprazan in Breast Milk
时间窗: Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).
Time to maximum observed concentration (actual midpoint of the interval in which Cmax was observed).
次要结局
- Total Amount of Vonoprazan Excreted in Breast Milk(Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).)
- Percentage of Vonoprazan Excreted in Breast Milk Relative to the Total Dose Received(Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).)
- Estimated Infant Daily Dose of Vonoprazan(Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).)
- Estimated Relative Infant Dose to the Total Maternal Dose Received of Vonoprazan(Pre-dose on Day 4, and at regularly scheduled intervals through 24 hours after the morning dosing (0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, and 18-24 hours).)