A Phase 1, Open-Label, Randomized, Single-Dose, 5-Period Crossover Study to Determine the Bioavailability of Two Vonoprazan Orally Disintegrating Tablet Formulations Administered Without Water or Mixed With Water and Administered Via a Syringe Relative to the Vonoprazan Tablet in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Maximum Observed Drug Concentration (Cmax) of Vonoprazan
研究概览
简要总结
The primary objective of this study is to assess the bioavailability (BA) of a single oral dose of two vonoprazan orally disintegrating tablet formulations (ODT-1 or ODT-2) administered without water or mixed with water and administered via a syringe relative to the vonoprazan tablet in healthy 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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The participant is 18 to 55 years of age, inclusive, at Screening.
- •The participant has a body mass index (BMI) 18 to 32 kg/m2, inclusive, at Screening.
- •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 electrocardiogram (ECG) results, and physical examination findings at Screening.
- •Female participants of reproductive 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) from signing the informed consent form (ICF) until 4 weeks after the last dose of study drug or be surgically sterile (ie, hysterectomy or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for 12 consecutive months and documented plasma follicle stimulating hormone [FSH] level >40 IU/mL during Screening).
- •Female participants must have a negative pregnancy test at Screening and upon Check-in.
- •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 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 a positive test result for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Check-in.
- •The participant has a history of a clinically significant neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality that may impact the ability of the subject to participate.
- •The participant has current or recent (within 6 months) gastrointestinal conditions that would be expected to influence the absorption of drugs (eg, history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis (EE)), frequent (more than once per week) occurrence of heartburn, or any surgical intervention.
- •The participant has any other clinically significant findings on physical examination, clinical laboratory abnormalities, and/or ECG results that preclude his/her 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 (CYP3A4) inducers) except acetaminophen (up to 2 g per day), 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 the end of confinement on Study Day
- •The participant has consumed grapefruit and/or grapefruit juice, Seville orange or Seville orange-containing products (eg, marmalade), or other food products that may be CYP3A4 inhibitors (eg, vegetables from the mustard green family [kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats) within 7 days before the first dose of study drug and/or is expected to be unable to abstain through the study.
- •The participant has consumed caffeine- or xanthine-containing products within 48 hours (or 5 half-lives) before the first dose of study drug and/or is unable to abstain through the study.
- •The participant is a smoker and/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 and/or drug addiction within the last year or excessive alcohol consumption (regular alcohol intake >21 units per week for male subjects and >14 units of alcohol per week for female subjects; 1 unit is equal to approximately ½ pint [200 mL] of beer, 1 small glass [100 mL] of wine, or 1 measure [25 mL] of spirits) or use of alcohol 48 hours 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 or 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 donated blood or blood products >450 mL within 30 days before the first dose of study drug.
- •The participant has a history of relevant drug and/or food allergies (ie, allergy to vonoprazan or excipients or any significant food allergy that could preclude a standard diet in the clinical unit).
- •The participant has received a study drug in another investigational study within 5-times the t1/2 of the study drug or 30 days of dosing, whichever is longer.
- •Female participants who are pregnant or lactating; intend to become pregnant before, during, or within 4 weeks after participating in this study; or intend to donate ova during this time period.
- •The participant is not suitable for entry into the study in the opinion of the investigator.
研究组 & 干预措施
Sequence A, B, C, D, E: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 with Water (Drug)
Sequence A, B, C, D, E: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 without Water (Drug)
Sequence A, B, C, D, E: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan (Reference) (Drug)
Sequence B, D, E, C, A: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 without Water (Drug)
Sequence B, D, E, C, A: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 with Water (Drug)
Sequence B, D, E, C, A: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan (Reference) (Drug)
Sequence C, E, B, A, D: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 without Water (Drug)
Sequence C, E, B, A, D: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 with Water (Drug)
Sequence C, E, B, A, D: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan (Reference) (Drug)
Sequence D, C, A, E, B: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 without Water (Drug)
Sequence D, C, A, E, B: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 with Water (Drug)
Sequence D, C, A, E, B: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan (Reference) (Drug)
Sequence E, A, D, B, C: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 without Water (Drug)
Sequence E, A, D, B, C: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan ODT-1 or ODT-2 with Water (Drug)
Sequence E, A, D, B, C: Vonoprazan 10 mg
Participants will be randomly assigned to 1 of 5 treatment sequences in a 1:1:1:1:1 ratio.
On the first day of each dosing period, participants will receive 1 of the following study treatments according to the treatment sequence they are randomly assigned to:
- Treatment A: Vonoprazan 10 mg ODT-1 without water
- Treatment B: Vonoprazan 10 mg ODT-1 mixed with water and administered via a syringe
- Treatment C: Vonoprazan 10 mg ODT-2 without water
- Treatment D: Vonoprazan 10 mg ODT-2 mixed with water and administered via a syringe
- Treatment E (reference): Vonoprazan 10 mg tablet.
There will be a washout interval of a minimum of 5 days between study drug dosing in each period.
干预措施: Vonoprazan (Reference) (Drug)
结局指标
主要结局
Maximum Observed Drug Concentration (Cmax) of Vonoprazan
时间窗: Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
Cmax of Vonoprazan was reported.
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Vonoprazan
时间窗: Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
AUC0-t of Vonoprazan was reported.
AUC From Time 0 Extrapolated to Infinity (AUC0-inf) of Vonoprazan
时间窗: Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose
AUC0-inf of Vonoprazan was reported.
次要结局
- Time to Maximum Observed Plasma Concentration (Tmax) of Vonoprazan(Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose)
- Time Until First Measurable Concentration in Plasma (Tlag) of Vonoprazan(Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose)
- Terminal Elimination Rate Constant (λz) of Vonoprazan(Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose)
- Terminal Phase Half-life (t1/2) of Vonoprazan(Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose)
- Apparent Oral Clearance (CL/F) of Vonoprazan(Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose)
- Apparent Volume of Distribution (Vz/F) of Vonoprazan(Day 1 of each 3-day treatment period: Within 15 minutes pre-dose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-dose)