A Phase 1, Open-Label Study to Assess Pharmacokinetics After Single Doses of Pociredir in Participants With Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 6
- 主要终点
- Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC(0-tlast)) of pociredir under fasted and fed conditions
研究概览
简要总结
This clinical trial is a study to evaluate the pharmacokinetics of the tablet formulation Pociredir in fasted and fed state participants with Sickle Cell Disease (SCD).
详细描述
The study is designed to assess the pharmacokinetics of the tablet formulation of pociredir under fasted conditions in up to approximately 12 study participants with SCD (Fasted Cohort). An additional cohort of up to approximately 12 study participants with SCD may be enrolled to evaluate the potential effect of food on the PK of the tablet formulation (Fed Cohort). The fasted cohort will be conducted first.
The study will include screening period: Day -28 to Day -2; In-patient confinement period: Days -1 to 3; check-in on day -1; single dose of pociredir on day 1; discharge on Day 3; outpatient visit: Day 4; end of study (EOS) visit: Days 8-11
Eligible participants who meet all inclusion and none of the exclusion criteria will be admitted to the clinical site on Day -1, the day before dosing. Participants may be discharged on Day 3 following completion of 48-hour PK sampling or may remain in-clinic through Day 4 if needed. Fasted Cohort: Participants will fast for at least 10 hours prior to dosing and remain fasted for 4 hours post-dose. Water intake will be restricted for 1 hour before and after administration of the investigational medicinal product (IMP). Fed Cohort (if conducted): Participants will fast for at least 10 hours prior to breakfast and will receive a standard high-fat breakfast starting 30 minutes before dosing.
Pharmacokinetic samples will be collected up to 72 hours post-dose. Participants are required to remain in-clinic for the first 48 hours post-dose and may return to the site for subsequent Outpatient and EOS visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented SCD at the time of screening, as confirmed through review of medical records or high-performance liquid chromatography (HPLC)/electrophoresis.
- •Participant, who if female and of childbearing potential, agrees to use 2 effective methods of contraception, one which must be highly effective, or practice abstinence starting at the time of the ICF signing to 90 days after the last dose of study drug, and, who if male, agrees to use condoms or practice abstinence from the time of ICF signing to 90 days after the last dose of study drug.
- •Total Hb ≥ 5.5 grams/deciliter (g/dL) and ≤ 12 g/dL (males) or ≤ 10.6 g/dL (females) at screening
- •Participant must meet all of the following laboratory values at screening:
- •Absolute neutrophil count ≥ 1.5 × 10^9/L (cells/liter)
- •Platelets ≥ 80 × 10^9/L
- •Absolute reticulocyte count > 100 × 10^9/L
- •Participants who meet all other inclusion and
排除标准
- •for this study, and per Investigator's recommendation may continue crizanlizumab, and/or L-glutamine, must be on a stable dose for at least 6 months
- •Exclusion Criteria:
- •Participant has had any of the following in the 14 days prior to dosing: major surgery, serious illness, infection (clinically significant bacterial, fungal, parasitic or viral infection which requires therapy), fever not resolved within 3 days and requiring treatment, or sickle cell complication requiring care from a medical provider in a hospital or emergency care setting.
- •Participant has a serious medical condition other than SCD that, in the opinion of the Investigator, would preclude them from participating in the study, or which is unresolved or requiring ongoing treatment.
- •Elective surgery planned for the time period of the study.
- •Use of any medications that induce or inhibit cytochrome P450 (CYP) 3A4, inhibit P-glycoprotein, breast cancer resistance protein, or multidrug and toxin extrusion protein 2-K, or are substrates of CYP2B6 within 14 days prior to first dose of study drug or anticipated need for any of these medications during the study.
- •Participation in any other study with an investigational agent within the past 30 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
- •For Fed Cohort Only: Participant has special dietary restrictions or inability to consume standard meals as required in the study.
- •Note: Other protocol specified criteria may apply.
研究组 & 干预措施
Fasted Cohort
Pociredir single dose tablet formulation under fasted conditions.
干预措施: Pociredir (Drug)
Fed Cohort
Pociredir single dose tablet formulation under fed conditions (after a high-fat breakfast).
干预措施: Pociredir (Drug)
结局指标
主要结局
Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC(0-tlast)) of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Area under the plasma concentration-time curve from time 0, extrapolated to infinity (AUC(0-inf)), of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Time to maximum plasma concentration (Tmax) of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Terminal disposition rate constant (λz) of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Terminal half-life (t1/2) of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Apparent volume of distribution during the terminal phase (Vz/F) of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Apparent clearance (CL/F) of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Plasma concentration of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Maximum plasma concentration (Cmax) of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
Area under the plasma concentration-time curve from time 0 to 24 hours (AUC(0-24)) of pociredir under fasted and fed conditions
时间窗: Day 1 through Day 4
次要结局
- Number of participants with treatment emergent adverse events (TEAEs) under fasted and fed conditions(Up to Day 11)
- Number of participants with clinically significant changes in safety assessments under fasted and fed conditions(Up to Day 11)
- Number of participants with clinically significant findings in clinical laboratory evaluations, vital signs, electrocardiogram (ECGs) and physical examination(Up to Day 11)
- Plasma concentration of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- Cmax of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- AUC(0-24) of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- AUC(0-tlast) of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- AUC(0-inf), under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- Tmax of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- λz of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- t1/2 of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- Vz/F of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)
- CL/F of pociredir under fasted and fed conditions compared to healthy participants(Day 1 through Day 4)