A Phase 1, 4-arm, Open-label, Drug-drug Interaction Trial to Evaluate the Pharmacokinetics of Repinatrabit Oral Tablets When Co-administered With Ethinyl Estradiol/Norethindrone, Metformin, Carbamazepine, Rosuvastatin, and Methotrexate in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- All Arms: Maximum Plasma Concentration (Cmax)
研究概览
简要总结
The purpose of this study is to assess the drug-drug interaction (DDI) of repinatrabit with ethinyl estradiol/norethindrone or norethisterone (EE/NE), metformin, rosuvastatin, carbamazepine, and methotrexate in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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 mass index (BMI) from 18 to 35 kilograms per square meter (kg/m^2) (inclusive).
- •Male and female (of non-childbearing potential) assigned at birth, inclusive of all gender identities. Arm 1 will only recruit biological females.
- •In good health as determined by:
- •Medical history
- •Physical examination
- •Serum chemistry, urinalysis, hematology, and serology tests
- •Willing to stay in the clinic for the required period and willing to be contacted for the safety follow-up via telephone contact.
- •Ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.
排除标准
- •Female participants of childbearing potential.
- •Female participants who have used HRT within 60 days or hormonal contraceptives within 14 days prior to Day 1 (Arm 1 only).
- •Clinically significant abnormality in past medical history, or at the screening physical examination, that in the investigator's or sponsor's opinion may place the participant at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug. This includes, but is not limited to, history of or concurrent cardiac, hepatic, renal, neurologic, endocrine, gastrointestinal, respiratory, hematologic, and immunologic disease or cholecystectomy.
- •For Arm 3, participants who test positive for HLA haplotypes associated with carbamazepine-induced hypersensitivity (HLA-B*15:02, HLA-A*31:01, and HLA-B*15:11).
- •Note: Other protocol-specified Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Arm 1: Repinatrabit + EE/NE
Participants will first receive a single dose of EE/NE, orally, followed by repinatrabit in combination with EE/NE or alone, up to Day 18.
干预措施: Repinatrabit (Drug)
Arm 1: Repinatrabit + EE/NE
Participants will first receive a single dose of EE/NE, orally, followed by repinatrabit in combination with EE/NE or alone, up to Day 18.
干预措施: EE/NE (Drug)
Arm 2: Repinatrabit + (Metformin + Rosuvastatin)
Participants will receive a single dose of metformin and rosuvastatin, orally, followed by repinatrabit in combination with metformin and rosuvastatin or alone, up to Day 9.
干预措施: Repinatrabit (Drug)
Arm 4: Repinatrabit + Methotrexate
Participants will receive a single dose of methotrexate, orally, followed by repinatrabit in combination with methotrexate or alone, up to Day 8.
干预措施: Methotrexate (Drug)
Arm 3: Repinatrabit + Carbamazepine
Participants will receive a single dose of repinatrabit, orally, followed by carbamazepine in combination with repinatrabit or alone, up to Day 15.
干预措施: Repinatrabit (Drug)
Arm 3: Repinatrabit + Carbamazepine
Participants will receive a single dose of repinatrabit, orally, followed by carbamazepine in combination with repinatrabit or alone, up to Day 15.
干预措施: Carbamazepine (Drug)
Arm 4: Repinatrabit + Methotrexate
Participants will receive a single dose of methotrexate, orally, followed by repinatrabit in combination with methotrexate or alone, up to Day 8.
干预措施: Repinatrabit (Drug)
Arm 2: Repinatrabit + (Metformin + Rosuvastatin)
Participants will receive a single dose of metformin and rosuvastatin, orally, followed by repinatrabit in combination with metformin and rosuvastatin or alone, up to Day 9.
干预措施: Rosuvastatin (Drug)
Arm 2: Repinatrabit + (Metformin + Rosuvastatin)
Participants will receive a single dose of metformin and rosuvastatin, orally, followed by repinatrabit in combination with metformin and rosuvastatin or alone, up to Day 9.
干预措施: Metformin (Drug)
结局指标
主要结局
All Arms: Maximum Plasma Concentration (Cmax)
时间窗: Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9
Cmax will be assessed for EE/NE in Arm 1, metformin and rosuvastatin in Arm 2, repinatrabit in Arm 3, and methotrexate in Arm 4 in this outcome measure
All Arms: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Observable Concentration at Time t (AUCt)
时间窗: Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9
AUCt will be assessed for EE/NE in Arm 1, metformin and rosuvastatin in Arm 2, repinatrabit in Arm 3, and methotrexate in Arm 4 in this outcome measure.
All Arms: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinfinity)
时间窗: Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9
AUCinfinity will be assessed for EE/NE in Arm 1, metformin and rosuvastatin in Arm 2, repinatrabit in Arm 3, and methotrexate in Arm 4 in this outcome measure.
次要结局
- All Arms: Number of Participants With Potentially Clinically Relevant Changes in Vital Signs(Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9)
- All Arms: Number of Participants With Potentially Clinically Relevant Changes in Clinical Laboratory Tests(Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9)
- All Arms: Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Arm 1: up to Day 25; Arm 2: up to Day 16; Arm 3: up to Day 22; Arm 4: up to Day 15)
- All Arms: Number of Participants With Potentially Clinically Relevant Changes in 12-Lead Electrocardiogram (ECG) Tests(Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9)
- All Arms: Time to Maximum (Peak) Plasma Concentration (Tmax)(Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9)
- All Arms: Apparent Clearance of Drug From Plasma After Extravascular Administration (CL/F)(Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9)
- All Arms: Volume of Distribution Following Extravascular Administration (Vz/F)(Arm 1: up to Day 19; Arm 2: up to Day 10; Arm 3: up to Day 16; Arm 4: up to Day 9)
- All Arms: Terminal Phase Elimination Half-Life (t1/2,z)(Arm 1: up to Day 19; Arm 2: up to Day 10, Arm 3: up to Day 13; Arm 4: up to Day 6)