A Phase 1, Open-Label, Two-Cohort Study to Assess the Effect of a Strong CYP3A4 Inducer on the Pharmacokinetics of Atumelnant and the Effect of Atumelnant on the Pharmacokinetics of CYP3A4, P-gp, and MATE1/2-K Substrates in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Cohort 1: Pharmacokinetics (AUC 0-last)
研究概览
简要总结
This study aims to evaluate the impact of strong CYP3A4 induction on the pharmacokinetics (PK) of atumelnant, as well as the effect of atumelnant on CYP3A4, P-gp, and MATE1/2-K substrates in healthy participants.
详细描述
This is a Phase 1, open-label, two-Cohort Study to assess the effect of a strong CYP3A4 inducer on the pharmacokinetics of atumelnant and the effect of atumelnant on the pharmacokinetics of CYP3A4, P-gp, and MATE1/2-K Substrates in healthy participants.
Approximately 20 healthy male and female participants adult male and female (of non-childbearing potential) participants will be enrolled in Cohort 1. Approximately 26 healthy male and female participants adult male and female (of non-childbearing potential) participants will be enrolled in Cohort 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult females of non-childbearing potential (Section 14.2) or healthy adult males, 19-55 years of age, inclusive, at the screening visit.
- •BMI ≥18.0 and ≤32.0 kg/m2 at the screening visit.
- •Is willing and able to comply with all study procedures and restrictions, including fasting and consumption of protocol-specified standardized meal for required study measurements; inpatient admission; follow-up contact; receipt of rescue therapy, if necessary; abstinence from tobacco, alcohol, drugs, and from strenuous unaccustomed exercise and sports (defined as greater than 30 minutes per day) during the study period.
- •Normal adrenocorticotropic hormone (ACTH)-stimulated cortisol test at the screening visit and does not have signs and symptoms of adrenal insufficiency as deemed by the PI or designee.
排除标准
- •Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
- •Female participant with a positive pregnancy test at the screening visit or at first check-in or who is lactating.
- •Female participant of childbearing potential.
- •Had prior treatment with atumelnant.
- •Participation in another clinical study within 30 days or received any investigational drug within 5 half-lives prior to the first dosing, whichever is longer. The time window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study.
- •History or presence of hypersensitivity or idiosyncratic reaction to the study interventions or related compounds.
- •Has a blood loss ≥500 mL or donated blood within 3 months prior to the first dosing.
- •Unable to refrain from or anticipates the use of any drugs, including prescription and non-prescription medications, herbal remedies, vitamin supplements, or other food supplements within 14 days or 5 half-lives prior to the first dosing, whichever is longer.
研究组 & 干预措施
Cohort 2
atumelnant, midazolam (CYP3A4 substrate), digoxin (P-gp substrate), metformin (MATE1/2-K substrate)
干预措施: Midazolam (Drug)
Cohort 2
atumelnant, midazolam (CYP3A4 substrate), digoxin (P-gp substrate), metformin (MATE1/2-K substrate)
干预措施: Atumelnant (Drug)
Cohort 1
atumelnant, carbamazepine (CYP3A4 Inducer)
干预措施: Carbamazepine (Drug)
Cohort 2
atumelnant, midazolam (CYP3A4 substrate), digoxin (P-gp substrate), metformin (MATE1/2-K substrate)
干预措施: Digoxin (Drug)
Cohort 1
atumelnant, carbamazepine (CYP3A4 Inducer)
干预措施: Atumelnant (Drug)
Cohort 2
atumelnant, midazolam (CYP3A4 substrate), digoxin (P-gp substrate), metformin (MATE1/2-K substrate)
干预措施: Metformin (Drug)
结局指标
主要结局
Cohort 1: Pharmacokinetics (AUC 0-last)
时间窗: Up to Day 34
Cohort 1: Pharmacokinetics (AUC 0-inf)
时间窗: Up to Day 34
Cohort 1: Pharmacokinetics (Cmax)
时间窗: Up to Day 34
Cohort 2: Pharmacokinetics (AUC 0-last)
时间窗: Up to Day 21
Cohort 2: Pharmacokinetics (AUC 0-inf)
时间窗: Up to Day 21
Cohort 2: Pharmacokinetics (Cmax)
时间窗: Up to Day 21
次要结局
- Cohort 1: Number of participants with Treatment Emergent Adverse Events(Up to Day 34)
- Cohort 2: Number of participants with Treatment Emergent Adverse Events(Up to Day 21)