A Phase 1, Open-label, 3-Period, Randomized 2-Sequence Study to Evaluate the Effect of Food and a Proton Pump Inhibitor on the Pharmacokinetics of VRN110755 in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC₀-inf) of VRN110755
研究概览
简要总结
This is a Phase 1, open-label, randomized, single-center study to evaluate the effect of food and a proton pump inhibitor (PPI) on the pharmacokinetics (PK) of VRN110755 in healthy adult participants. The primary aim of this study is to assess the impact of food and rabeprazole co-administration on the systemic exposure of VRN110755. Safety and tolerability will also be evaluated.
详细描述
The study consists of two treatment sequences in a 3-period, crossover design. Approximately 24 healthy adult participants will be randomized 1:1 to one of the following sequences:
Sequence 1: Participants will receive VRN110755 80 mg orally in the fasted state (Period 1), then in the fed state (Period 2), and finally in the fed state with 5 days of rabeprazole pre-treatment (Period 3).
Sequence 2: Participants will receive VRN110755 80 mg orally in the fed state (Period 1), then in the fasted state (Period 2), and finally in the fasted state with 5 days of rabeprazole pre-treatment (Period 3).
Rabeprazole 20 mg will be administered orally once daily for 5 consecutive days prior to the final dosing of VRN110755 in Period 3.
All participants will remain under clinical observation for safety monitoring and pharmacokinetic sampling throughout each period. Blood and urine samples will be collected at defined intervals for the analysis of VRN110755 and its metabolites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female participants aged between 18 and 65 years, inclusive, at the time of informed consent.
- •In good general health, with no significant medical history and no clinically significant abnormalities on physical examination, as determined by the investigator.
- •Body mass index (BMI) between 18.0 and 32.0 kg/m², and weight ≥ 50 kg at screening.
- •Clinical laboratory values within normal ranges, unless deemed not clinically significant by the investigator.
- •Female participants of childbearing potential who are sexually active with a male partner must agree to use highly effective contraception methods from screening through 6 months after the last dose of investigational product.
- •Female participants must have a negative pregnancy test at screening and pre-dose.
- •Women not of childbearing potential must be surgically sterile or postmenopausal for ≥12 months.
- •Male participants must agree to use barrier contraception in conjunction with a highly effective method if engaging with women of childbearing potential, from screening through 6 months after the last dose.
- •Male participants must not donate sperm, and female participants must not donate ova, from the first dose through 6 months after the last dose.
- •Able and willing to comply with study procedures and site visits.
- •Able and willing to provide written informed consent before any study procedures are performed.
排除标准
- •Any significant medical or psychiatric condition that may interfere with study participation or interpretation of results, as determined by the investigator.
- •Clinically significant abnormal ECG findings, including QTcF > 450 ms (males) or > 470 ms (females).
- •Abnormal vital signs at screening (e.g., systolic BP > 140 or < 90 mmHg, diastolic BP > 90 or < 60 mmHg, or history of symptomatic hypotension).
- •Active liver disease, or AST/ALT > 1.5 × upper limit of normal.
- •Known or suspected gastrointestinal disorders that may interfere with drug absorption (e.g., IBD, chronic diarrhea, malabsorption).
- •Positive urine drug screen or alcohol breath test at screening.
- •Regular alcohol use >14 standard drinks/week or >3 drinks/day.
- •Positive test for HIV, Hepatitis B (HBsAg), or Hepatitis C antibody.
- •History of severe allergies or anaphylaxis, or known hypersensitivity to study drug components.
- •Recent infections requiring parenteral antibiotics within 6 months before first dose.
- •Vaccination with live vaccine within 4 weeks prior to first dose.
- •Blood donation >400 mL within 60 days, or component donation within 30 days prior to dosing.
- •eGFR ≤ 90 mL/min/1.73 m² at screening.
- •Use of nicotine-containing products within 7 days before dosing or unwillingness to abstain during the study.
- •Use of prescription/OTC medications, herbal products, or supplements within 14 days prior to dosing, unless approved by the investigator.
- •Use of CYP3A4 inhibitors/inducers or medications affecting metabolism of VRN110755 within 14 days prior to dosing.
- •Unwillingness to follow dietary restrictions (e.g., cannot consume high-fat meals).
- •Use of proton pump inhibitors, H2 blockers, or antacids within 8 weeks prior to first dose (except planned rabeprazole use in study).
- •Known hypersensitivity to PPIs (e.g., rabeprazole).
- •Planned or current participation in another investigational trial or use of another investigational product within 30 days or 5 half-lives.
- •Poor peripheral venous access.
- •Any condition that, in the opinion of the investigator, would jeopardize participant safety or interfere with study compliance or data integrity.
研究组 & 干预措施
Sequence 2: Fed → Fasted → Fasted with PPI
Participants in this sequence will receive VRN110755 80 mg orally under the following conditions across three periods:
Period 1: Fed state (standard high-fat meal) Period 2: Fasted state Period 3: Fasted state after 5 days of rabeprazole 20 mg daily
干预措施: Rabeprazole (Drug)
Sequence 1: Fasted → Fed → Fed with PPI
Participants in this sequence will receive VRN110755 80 mg orally under the following conditions across three periods:
Period 1: Fasted state Period 2: Fed state (standard high-fat meal) Period 3: Fed state after 5 days of rabeprazole 20 mg daily
干预措施: VRN110755 (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC₀-inf) of VRN110755
时间窗: Up to 312 hours post-dose (for each treatment period)
To evaluate the effect of food and rabeprazole on the extent of systemic exposure of VRN110755 by measuring AUC₀-inf under fasted, fed, and PPI conditions.
Maximum Observed Plasma Concentration (Cmax) of VRN110755
时间窗: Up to 312 hours post-dose (for each treatment period)
To assess the peak plasma concentration of VRN110755 under different dosing conditions (fasted, fed, fed/fasted + PPI).
Time to Maximum Observed Concentration (Tmax) of VRN110755
时间窗: Up to 312 hours post-dose (for each treatment period)
To assess the time to reach peak concentration of VRN110755 after single-dose oral administration under different conditions.
Comparison of Pharmacokinetic Parameters (AUC and Cmax Ratios) Across Treatment Conditions
时间窗: Up to 312 hours post-dose (for each treatment period)
To compare AUC and Cmax values of VRN110755 between fed vs. fasted, and PPI vs. non-PPI conditions using statistical analysis.
次要结局
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(From Day 1 of Period 1 through the End of Study (approximately 76 days per participant))
- Incidence of Serious Adverse Events (SAEs)(From Day 1 of Period 1 through the End of Study (approximately 76 days per participant))
- Number of Participants with Abnormal Clinical Laboratory Test Results(Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48))
- Change in 12-lead ECG Parameters From Baseline(Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48))
- Change in Systolic Blood Pressure From Baseline(Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).)
- Change in Diastolic Blood Pressure From Baseline(Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).)
- Change in Pulse Rate From Baseline(Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).)
- Change in Respiratory Rate From Baseline(Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).)
- Change in Tympanic Temperature From Baseline(Baseline (Day 1), pre-dose on Day 15 and Day 34, and End-of-Study Visit (Day 48).)
- Cumulative Amount Excreted (Ae) of VRN110755(0 to 24 hours post-dose in each study period.)
- Fraction Excreted (Fe) of VRN110755(0 to 24 hours post-dose in each study period.)
- Renal Clearance (CLr) of VRN110755(0 to 24 hours post-dose in each study period.)