A Phase 1, Randomized, Open-label Study to Characterize the Pharmacokinetics, Pharmacodynamics, and Safety of Vamifeport After Multiple Oral Administration of One Immediate-release Formulation and After Single and Multiple Oral Administration of Two Prolonged-release Formulations in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Plasma concentration-time course profiles of vamifeport
研究概览
简要总结
This is a phase 1, single-center, randomized, open-label study to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and safety of vamifeport after multiple oral administrations of one immediate-release (IR) formulation and after single and multiple oral administrations of two prolonged-release (PR) formulation in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged greater than or equal to (>=) 18 to less than or equal to (<=) 60 years when providing written informed consent.
- •Healthy, as determined by the investigator based on review of defined assessments during Screening.
- •Body weight between 50 and 100 kilograms (kg) (inclusive) and body mass index within the range 18.0 to 32.0 kg per meter squared (kg/m2) (inclusive) at Screening and Day -1.
排除标准
- •Any clinically relevant abnormal 12-lead ECG finding at Screening or Day -1 (as deemed by the investigator).
- •Serum ferritin of < 30 nanograms per milliliter (ng/mL) or > 300 ng/mL for assigned male at birth (AMAB) subjects or <16 ng/mL or > 300 ng/mL for assigned female at birth (AFAB) subjects at Screening or Day -
- •Hemoglobin < 13 grams per deciliter (g/dL) (8.1 millimoles per liter [mmol/L]) for AMAB subjects or 12 g/dL (7.5 mmol/L) for AFAB subjects at Screening or Day -
- •Blood draw or donation of blood (>= 450 mL) within 3 months before Screening, plasma from 2 weeks before Screening, or platelets from 6 weeks before Screening.
研究组 & 干预措施
Treatment Period 1: Vamifeport IR Formulation Dose Level 1
Participants will receive multiple doses of Vamifeport Immediate-release (IR) formulation at Dose level 1.
干预措施: Vamifeport IRF (Drug)
Treatment Period 2: Vamifeport PR1 Dose Level 2
Participants will receive multiple doses of Vamifeport Prolonged-release formulation 1 (PR1) at Dose level 2.
干预措施: Vamifeport PR1 (Drug)
Treatment Period 2: Vamifeport PR2 Dose Level 2
Participants will receive multiple doses of Vamifeport Prolonged-release formulation 2 (PR2) at Dose level 2.
干预措施: Vamifeport PR2 (Drug)
Treatment Period 3: Vamifeport PR1 Dose Level 3
Participants will receive a single dose of Vamifeport PR1 at Dose level 3.
干预措施: Vamifeport PR1 (Drug)
Treatment Period 3: Vamifeport PR2 Dose Level 3
Participants will receive a single dose of Vamifeport PR2 at Dose level 3.
干预措施: Vamifeport PR2 (Drug)
Treatment Period 4: Vamifeport PR1 Dose Level 3
Participants will receive a single dose of Vamifeport PR1 at Dose level 3.
干预措施: Vamifeport PR1 (Drug)
Treatment Period 4: Vamifeport PR2 Dose Level 3
Participants will receive a single dose of Vamifeport PR2 at Dose level 3.
干预措施: Vamifeport PR2 (Drug)
结局指标
主要结局
Plasma concentration-time course profiles of vamifeport
时间窗: Treatment Period (TP) 2: Before and after dosing on Day 4 (up to 12 hours), Day 8 (up to 48 hours), Before dosing on Day 5, 6, 7 TP 3: Before and after dosing on Day 13 (up to 48 hours) TP 4: Before and after dosing on Day 16 (up to 48 hours)
Maximum plasma concentration (Cmax) of first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP2: Before, and up to 48 hours after, both the first and the last dose
Time to reach Cmax (Tmax) of first and last dose vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 48 hours after, both the first and the last dose
Area under the plasma concentration curve from time zero to 12 hours (AUC0-12) of first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 48 hours after, both the first and the last dose
Trough concentration (Ctrough) of first dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: Before and up to 24 hours after the first dose in TP2
AUC from time zero to infinity (AUC0-inf) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 48 hours after last dose
AUC from time zero to time tlast (AUC0-last) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 48 hours after last dose
AUC from time zero to 8 hours (AUC0-8) and 24 hours (AUC0-24) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 8 and 24 hours after last dose
Plasma concentration at 12 hours (Conc [t=12]) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before and up to 12 hours after last dose
Apparent clearance (CL/F) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 48 hours after last dose
Apparent volume of distribution at steady state (Vss/F) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 48 hours after last dose
Accumulation ratio (Rac) of Cmax between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 48 hours after first and last dose
Rac(Ctrough/Conc[t=12]) between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 12 hours after first and last dose
Rac (AUC0-12) between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 12 hours after first and last dose
Half-life (t1/2) after last dose of vamifeport PR1 and PR2 in Treatment Period 2
时间窗: TP 2: Before, and up to 48 hours after last dose
Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 48 hours after dosing, in TP3 and TP4
Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 48 hours after dosing, in TP3 and TP4
AUC0-last of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 48 hours after dosing, in TP3 and TP4
AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 48 hours after dosing, in TP3 and TP4
AUC0-8, AUC0-12 and AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 8, 12 and 24 hours after dosing, in TP3 and TP4
Plasma Concentration at 8 hours (Conc [t=8]), 12 hours (Conc [t=12]) and 24 hours (Conc [t=24]) of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 8, 12 and 24 hours after dosing, in TP3 and TP4
CL/F of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 48 hours after dosing, in TP3 and TP4
t1/2 of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 48 hours after dosing, in TP3 and TP4
Apparent volume of distribution (Vz/F) of vamifeport PR1 and PR2 in Treatment Period 3 and 4
时间窗: Before and up to 48 hours after dosing, in TP3 and TP4
次要结局
- Percentage of participants with TEAE, AE by severity, AE related to vamifeport, and serious AE(Up to 25 days after treatment)
- Number of participants with clinically significant change from Baseline in clinical laboratory safety tests, 12 lead Electrocardiogram (ECG), and vital signs(At baseline and up to 25 days after treatment)
- AUC0-12 of vamifeport PR1 and PR2 in Treatment Period 3 and 4(Before and up to 12 hours after dosing, in TP3 and TP4)
- AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4(Before and up to 48 hours after dosing, in TP3 and TP4)
- Number of participants with treatment-emergent (TE): adverse event (AE), AE by severity, AE related to vamifeport, and serious AE(Up to 25 days after treatment)
- AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4(Before and up to 24 hours after dosing, in TP3 and TP4)
- Conc (t=12) of vamifeport PR1 and PR2 in Treatment Period 3 and 4(Before and up to 12 hours after dosing, in TP3 and TP4)
- Conc (t=24) of vamifeport PR1 and PR2 in Treatment Period 3 and 4(Before and up to 24 hours after dosing, in TP3 and TP4)
- Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4(Before and up to 48 hours after dosing, in TP3 and TP4)
- Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4(Before and up to 48 hours after dosing, in TP3 and TP4)
- Absolute values of serum iron(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- Absolute values of transferrin saturation (TSAT)(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- Change from baseline of serum iron(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- Change from baseline of TSAT(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- Maximum percentage change from baseline (Emax) of serum iron(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- Emax of TSAT(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- Time to Emax (TEmax) of serum iron(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- TEmax of TSAT(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- Time below baseline of serum iron(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- Time below baseline of TSAT(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- AUC below baseline of serum iron(Before and up to 48 hours after dosing in TP2, TP3 and TP4)
- AUC below baseline of TSAT(Before and up to 48 hours after dosing in TP2, TP3 and TP4)