A Phase I, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study and Food Effect Study of Oral RP7214, a DHODH Inhibitor, in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Assessments of Adverse Events (AEs)
研究概览
简要总结
This is a randomized, double-blind study to evaluate the safety, tolerability and PK of single and multiple ascending oral doses of RP7214. The relative bioavailability in fed and fasting conditions will also be evaluated for RP7214. The study comprises three parts; Part 1: Single ascending dose, Part 2: Multiple ascending dose and Part 3: Food effect.
详细描述
There are three escalating cohorts in SAD part and two escalating cohorts in MAD part. In each cohort, six eligible healthy volunteers will be randomized to receive either RP7214 or placebo in 2:1 ratio. Within each cohort, two sentinel subjects (RP7214 and Placebo) will be dosed first for assessment of safety and tolerability. The safety data of at least 48 hrs will be reviewed to confirm safety of sentinel subjects after which the remaining four subjects will be dosed. Food effect study is a randomized, 2-treatment, 2-period, 2-sequence, crossover study in 12 HVs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Subjects willing and able to provide informed consent for the trial
- •Male and non-childbearing female subjects aged 18 to 55 years
- •Healthy subjects as determined by pre-study medical history, vitals, physical examination and 12-lead ECG, and clinical laboratory tests within the normal reference ranges or clinically acceptable to investigator
- •Non-tobacco user/non-smokers or ex-smokers defined as someone who has stopped smoking cigarettes for at least 6 months.
- •Negative screen for drugs of abuse and alcohol at screening and on admission.
- •Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive.
- •A male subject who is able to procreate should agree to use one of the accepted contraceptives and agree to refrain from donating sperm for at least 3 months after dosing; and should not father a child during this period.
- •Female subjects should be of non-childbearing potential.
- •Willing and able to understand the nature of this study, comply with the study procedures as required by the study protocol.
排除标准
- •Subjects with evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies) at the time of screening.
- •Positive screen for hepatitis-B surface antigen (HBsAg), antibodies to the hepatitis C (HCV) or antibodies to the human immunodeficiency virus (HIV) 1 and
- •Subjects who received or are on Covid-19 directed prophylaxis (e.g. chloroquine or hydroxychloroquine) in last two weeks or 5x half-lives of the drug, whichever is shorter, prior to dosing.
- •Subjects participating in another clinical study or use of any investigational product in last 30 days or 5x half-lives of the drug, whichever is shorter, prior to dosing.
- •Pregnant or lactating females.
- •Clinically significant abnormalities in physical examination and/or in laboratory tests (including hematology and chemistry panels, urinalysis) as assessed by the Investigator.
- •Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulations/procedures.
- •Concomitant disease or condition that could interfere with the conduct of the study, or for which the treatment could interfere with the conduct of the study, or that would in the opinion of investigator, pose an unacceptable risk to the subject in this study.
- •Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
研究组 & 干预措施
RP7214, Single and multiple doses
In Part 1 up to 3 cohorts with single ascending doses of RP7214 at 100 mg QD, 200 mg QD and 400 mg QD.
In Part 2 up to 2 cohorts with multiple ascending doses of RP7214 at 200 mg BID, 400 mg BID.
干预措施: RP7214 (Drug)
Placebo, Single and multiple doses
In Part 1 up to 3 cohorts and in Part 2 up to 2 cohorts with matching placebo to RP7214 tablet
干预措施: Placebo (Drug)
结局指标
主要结局
Assessments of Adverse Events (AEs)
时间窗: Day1 - day15
次要结局
- RP7214 Cmax(0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose)
- RP7214 t½(0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose)
- RP7214 Tmax(0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose)
- RP7214 AUC0-inf(0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs post dose)