NCT06342700已完成1 期
A Randomized, Open-label, Single-dose, 4-period, 4--sequence, Crossover Phase I Relative Bioavailability Study Comparing Crystalline Formulation Tablet Versus Reference Amorphous Formulation Tablet of Rilzabrutinib (SAR444671) in Fasted and Fed Conditions in Healthy Male and Female Participants
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Relative bioavailability as assessed by rilzabrutinib Cmax following administration of the test and reference formulations in the fasted state
研究概览
简要总结
This is a cross-over, Phase 1, 4-arm study. The purpose of this study is to measure the relative bioavailability and food effect of crystalline formulation rilzabrutinib and amorphous formulation rilzabrutinib in healthy male and female participants aged 18 to 55 years of age.
The total study duration per participant is expected to be up to 36 days, including:
- Screening: up to 4 weeks
- Treatment periods: once successfully screened, enrolled participants will be randomized to 1 of 4 treatment sequences with 4 single dose treatment periods.
- Washout: One day washout is planned after each treatment period hence providing 2 days between doses.
- Safety follow-up: participants will be asked to participate in an end-of-study safety assessment upon discharge from the clinical study unit, ie, on Day 8 of the study.
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
- •Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0 kg, inclusive, if female, body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive
- •Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy participant. Hepatic transaminases (aspartate aminotransferase, alanine aminotransferase) should not exceed 1.25 × the upper laboratory norm (ULN); total bilirubin should not exceed 1 × ULN
- •Willing to abstain from using tobacco or nicotine-containing products or consuming alcohol from check-in (Day -1) until discharge at end-of-study visit
- •Willing to abstain from taking any prescription drugs, dietary supplements, or non-prescription drugs within 14 days or 5 half-lives, whichever, is longer, prior to the first dose of study drug through the follow-up phone call. Use of hormonal contraception and aspirin (at doses of ≤2000 mg/day) or ibuprofen (at doses of ≤1200 mg/day) are allowed prior to and during the study
- •Negative urine drug/alcohol testing at screening and check-in (Day -1). Screening urine drug/alcohol testing may be repeated once if deemed appropriate by the site Investigator
- •Willing to abstain from consuming grapefruit, star fruit, or Seville orange-containing products from 14 days prior to first dose of study drug until discharge from the clinical study unit
排除标准
- •Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), infectious disease, or signs of acute illness
- •Participant has clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnea, loss of taste and smell, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening. Participant who had severe course of COVID-19 (ie, hospitalization, extracorporeal membrane oxygenation [ECMO], mechanically ventilated)
- •Participant has a positive test result for SARS-CoV-2 (measured via Real-time Reverse Transcriptase Polymerase Chain Reaction [RT-PCR] or Rapid Antigen Test [RAT])
- •Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month)
- •Blood donation, any volume, within 1 month before inclusion
- •Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure <30 mmHg within 3 minutes when changing from supine to standing position
- •Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician. Participants with known hypersensitivity to any component of the IMP formulation or allergic disease diagnosed and treated by a physician
- •History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis)
- •Regular intake of nicotine (via patch, smoking, vaping or other forms) more than 10 mg per day (based on the average nicotine content of 10-12 mg of nicotine per cigarette and inhalation of up to 2 mg of nicotine per cigarette), and unable to stop smoking during the study (occasional smoker can be enrolled)
- •Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day)
- •If female, pregnancy (defined as positive β-HCG blood test), or breast-feeding
- •Any medication (including St John's Wort or ginseng) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, with the exception of aspirin/ibuprofen, hormonal contraception, and menopausal hormone replacement therapy
- •Any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion:
- •Non-live vaccines, including COVID-19: last administration of a vaccine within 4 weeks before randomization
- •Live vaccines: last administration of a vaccine within 3 months before randomization
- •Positive result on any of the following tests: hepatitis B surface antigen (HBs Ag), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab)
- •Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates)
- •Positive alcohol breath or alcohol urine test
- •Positive pregnancy test
- •Gilbert's Syndrome
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Treatment A: SAR444671 amorphous fasted
Active Comparator
Participants will receive single oral dose of amorphous tablet formulation rilzabrutinib (SAR444671) under fasted conditions on Day 1 for one period
干预措施: Rilzabrutinib amorphous form (Drug)
Treatment B: SAR444671 crystalline fasted
Experimental
Participants will receive single oral dose of crystalline tablet formulation rilzabrutinib (SAR444671) under fasted conditions on Day 1 for one period
干预措施: Rilzabrutinib crystalline form (Drug)
Treatment C: SAR444671 amorphous fed
Active Comparator
Participants will receive single oral dose of amorphous tablet formulation rilzabrutinib (SAR444671) under fed conditions on Day 1 for one period
干预措施: Rilzabrutinib amorphous form (Drug)
Treatment D: SAR444671 crystalline fed
Experimental
Participants will receive single oral dose of crystalline tablet formulation rilzabrutinib (SAR444671) under fed conditions on Day 1 for one period
干预措施: Rilzabrutinib crystalline form (Drug)
结局指标
主要结局
Relative bioavailability as assessed by rilzabrutinib Cmax following administration of the test and reference formulations in the fasted state
时间窗: Day 1 to Day 8
Cmax: maximum plasma concentration
Relative bioavailability as assessed by rilzabrutinib AUC following administration of the test and reference formulations in the fasted state
时间窗: Day 1 to Day 8
AUC: area under the plasma concentration versus time curve extrapolated to infinity
Relative bioavailability as assessed by rilzabrutinib AUClast following administration of the test and reference formulations in the fasted state
时间窗: Day 1 to Day 8
AUClast: area under the plasma concentration versus time curve from time zero to the last measurable concentration
次要结局
- Relative bioavailability as assessed by rilzabrutinib AUC following administration of the test and reference formulations in the fed state(Day 1 to Day 8)
- Food effects as assessed by rilzabrutinib Cmax following administration of the test and reference formulations under the fed versus fasted state(Day 1 to Day 8)
- Relative bioavailability as assessed by rilzabrutinib Cmax following administration of the test and reference formulations in the fed state(Day 1 to Day 8)
- Relative bioavailability as assessed by rilzabrutinib AUClast following administration of the test and reference formulations in the fed state(Day 1 to Day 8)
- Food effects as assessed by rilzabrutinib AUClast following administration of the test and reference formulations under the fed versus fasted state(Day 1 to Day 8)
- Food effects as assessed by rilzabrutinib AUC following administration of the test and reference formulations under the fed versus fasted state(Day 1 to Day 8)
- Number of participants with adverse events, treatment-emergent adverse events, serious adverse events and adverse events of special interest(Day 1 to Day 8)
研究者
研究点 (1)
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