A First-in-human, Participant and Investigator-blinded, Randomized, Placebo-controlled, Single-and Multiple-Ascending Dose Study With Drug-Drug Interaction, to Investigate the Safety, Tolerability, and Pharmacokinetic Profile of AB521, in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This study will evaluate the safety and tolerability, pharmacokinetic, and pharmacodynamic profile, and drug-drug interaction (DDI) of casdatifan in healthy participants.
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
- •Participants who are healthy volunteers (in the opinion of the investigator) as determined by pre-study medical history, physical examination, vital signs, and 12-lead electrocardiogram (ECG)
- •All clinical laboratory tests of blood and urine must be within the normal range or show no clinically relevant excursions from the normal range as judged by Principal Investigator at screening and admission.
- •Screening and randomization hemoglobin ≥for males and females is as follows:
- •SAD: male and female hemoglobin level ≥ 12.5 grams/ deciliters (g/dL) (7.7 millimoles/liters [mmol/L])
- •MAD and DDI: male hemoglobin level ≥ 14.2 g/dL (8.8 mmol/L) and female hemoglobin level ≥ 12.5 g/dL (7.7 mmol/L).
- •Participants should have adequate peripheral venous access.
- •Body weight of 45 kilograms (kg) or greater and body mass index within the range of 18 to 32 kg/meters squared (m^2) (inclusive)
- •Male participants must be vasectomized and have been vasectomized for at least 3 months prior to screening visit with confirmed history of azoospermia subsequent to the vasectomy procedure
- •Contraceptive use should be consistent with local regulations
排除标准
- •Has any (acute or chronic [including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection]) medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the study participant's ability to participate in this study
- •Has history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, cerebrovascular, neurological, or other major disorders capable of significantly altering the absorption, metabolism, or elimination of investigational drug; constituting a risk when taking the study intervention; or interfering with the interpretation of data in the opinion of the investigator
- •Abnormal blood pressure (BP) or pulse measurements at the Screening Visit or Day -2/-1 (Admission) in a supine position after 5 minutes of rest as follows: mean systolic BP ≥139 millimeters of mercury (mm Hg) or mean diastolic BP ≥89 mm Hg; mean pulse < 40 beats per minute (bpm) or > 100 bpm.
- •Liver enzyme test results: Alanine aminotransferase, aspartate aminotransferase, bilirubin, or alkaline phosphatase >1.0x the upper limit of normal
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities
- •Has 12-lead electrocardiogram with changes considered to be clinically significant at the Screening Visit or day of admission
研究组 & 干预措施
SAD-casdatifan Dose 1
Participants will receive "Dose 1" of casdatifan orally with water under fasting conditions.
干预措施: casdatifan (Drug)
SAD-casdatifan Dose 2
Participants will receive "Dose 2" of casdatifan orally with water under fasting conditions.
干预措施: casdatifan (Drug)
SAD-casdatifan Dose 3
Participants will receive "Dose 3" of casdatifan orally with water under fasting conditions.
干预措施: casdatifan (Drug)
SAD-casdatifan Dose 4
Participants will receive "Dose 4" of casdatifan orally with water under fasting conditions.
干预措施: casdatifan (Drug)
SAD-Placebo
Participants will receive matching placebo orally with water under fasting conditions.
干预措施: Placebo (Drug)
MAD-casdatifan Dose 1
Participants will receive "Dose 1" of casdatifan orally with water under fasting conditions.
干预措施: casdatifan (Drug)
MAD-casdatifan Dose 2
Participants will receive "Dose 2" of casdatifan orally with water under fasting conditions.
干预措施: casdatifan (Drug)
MAD-Placebo
Participants will receive matching placebo orally with water under fasting conditions.
干预措施: Placebo (Drug)
DDI-casdatifan Dose + Midazolam
Participants will receive highest safe dose level of casdatifan from MAD and midazolam orally with water under fasting conditions
干预措施: casdatifan (Drug)
DDI-casdatifan Dose + Midazolam
Participants will receive highest safe dose level of casdatifan from MAD and midazolam orally with water under fasting conditions
干预措施: Midazolam (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to 21.5 Weeks
Number of Participants With Abnormal Changes From Baseline in Laboratory Parameter Values
时间窗: Baseline; Up to 21.5 Weeks
Number of Participants With Abnormal Changes from Baseline in Vital Sign Values
时间窗: Baseline; Up to 21.5 Weeks
Maximum Observed Plasma Concentration (Cmax) of casdatifan
时间窗: multiple timepoints up to approximately 21.5 Weeks
Area Under the Plasma Concentration Time Curve From Hour 0 to the Last Sample With Measurable Plasma Concentrations (AUClast) of casdatifan
时间窗: multiple timepoints up to approximately 21.5 Weeks
Time of Occurrence of Cmax (tmax) of casdatifan
时间窗: multiple timepoints up to approximately 21.5 Weeks
Apparent Terminal Elimination Rate Constant (λz) of casdatifan
时间窗: multiple timepoints up to approximately 21.5 Weeks
Terminal Half-Life (t1/2) of casdatifan
时间窗: multiple timepoints up to approximately 21.5 Weeks
Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of casdatifan
时间窗: multiple timepoints up to approximately 21.5 Weeks
Apparent Volume of Distribution of casdatifan
时间窗: multiple timepoints up to approximately 21.5 Weeks
Apparent Total Body Clearance of casdatifan
时间窗: multiple timepoints up to approximately 21.5 Weeks
次要结局
- Maximum Observed Plasma Concentration (Cmax) of midazolam and 1 hydroxymidazolam(multiple timepoints up to approximately 21.5 Weeks)
- Area Under the Plasma Concentration Time Curve From Hour 0 to the Last Sample With Measurable Plasma Concentrations (AUClast) of midazolam and 1 hydroxymidazolam(multiple timepoints up to approximately 21.5 Weeks)
- Time of Occurrence of Cmax (tmax) of midazolam and 1 hydroxymidazolam(multiple timepoints up to approximately 21.5 Weeks)
- Apparent Terminal Elimination Rate Constant (λz) of midazolam and 1 hydroxymidazolam(multiple timepoints up to approximately 21.5 Weeks)
- Terminal Half-Life (t1/2) of midazolam and 1 hydroxymidazolam(multiple timepoints up to approximately 21.5 Weeks)
- Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of midazolam and 1 hydroxymidazolam(multiple timepoints up to approximately 21.5 Weeks)
- Apparent Volume of Distribution of midazolam and 1 hydroxymidazolam(multiple timepoints up to approximately 21.5 Weeks)
- Apparent Total Body Clearance of midazolam and 1 hydroxymidazolam(multiple timepoints up to approximately 21.5 Weeks)