A Phase 1, Single-center, Open-label, Fixed-sequence, 2-period Study in Healthy Adult Subjects to Evaluate the Effect of Gastric pH on Acalabrutinib Pharmacokinetics
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib
研究概览
简要总结
This study will evaluate the effect of gastric pH on acalabrutinib pharmacokinetics in healthy participants.
详细描述
This is a 2-period study done under fasting conditions. Participants will receive an oral wireless motility/pH capsule (SmartPill®) followed immediately by a single 100 mg oral dose of acalabrutinib on Day 1 of Period 1 and Period 2 (ie, Day 1 and Day 4, respectively). There will be 72 hours of washout between Day 1 dosing of each period. Participants will be contacted approximately 14 days after the last dose of study drug for adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 是
入选标准
- •Continuous nonsmoker who has not used nicotine-containing products for >= 3 months before the first dose.
- •Body mass index (BMI) >= 18.0 and <= 32.0 kg/m^2 at screening.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the principal investigator. Liver function tests, and serum bilirubin, must be <= upper limit of normal range (ULN) at screening.
- •Minimum of 1 bowel movement per day for >= 3 months before enrollment.
- •Women must be of non-childbearing status and must have negative serum pregnancy test results.
- •Men of reproductive potential to follow protocol defined contraception methods.
排除标准
- •Participant 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.
- •Participant has any of the following contraindications for the SmartPill: A history of gastric bezoars, swallowing disorder, suspected or known strictures, fistulas or physiological/mechanical gastrointestinal (GI) obstruction, history of GI surgery within 3 months of administration, severe dysphagia to food or pills, Crohn's disease or diverticulitis, cardiac pacemakers or other implanted electromedical devices.
- •History or presence of alcoholism or drug abuse within the past 2 years before screening
- •History of bleeding diathesis
- •History of gastric motility disorder for example delayed gastric emptying, dumping syndrome, or irritable bowel disease.
- •History of constipation within the last year before enrollment
- •Currently experiencing, or experienced within 2 weeks of enrollment, Grade 2 diarrhea
- •Women who are pregnant or breastfeeding
- •Positive urine drug or alcohol results at screening or check-in
- •Positive urine cotinine at screening.
- •Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- •Seated blood pressure is < 90/40 mmHg or > 140/90 mmHg at screening.
- •Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
- •Have been on a diet incompatible with the on study diet, in the opinion of the principal investigator (PI), within the 28 days before the first dose of study drug, and throughout the study.
- •Unable to refrain from or anticipates the use of protocol defined medications.
- •History or presence of liver disease and clostridium difficile-associated diarrhea.
研究组 & 干预措施
SmartPill® + Acalabrutinib
Participants will receive 1 SmartPill® capsule followed immediately by a single oral dose of acalabrutinib 100 mg capsule on Day 1 (Period 1) and Day 4 (Period 2). There will be 72 hours of washout between acalabrutinib dosing of each period.
干预措施: Acalabrutinib (Drug)
SmartPill® + Acalabrutinib
Participants will receive 1 SmartPill® capsule followed immediately by a single oral dose of acalabrutinib 100 mg capsule on Day 1 (Period 1) and Day 4 (Period 2). There will be 72 hours of washout between acalabrutinib dosing of each period.
干预措施: SmartPill® (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib
时间窗: pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Effect of Gastric pH and Emptying Rate on Acalabrutinib PK Parameters (Area Under Concentration-time Curve [AUC] From Time 0 to Last Measurable Concentration, AUC From Time 0 to Infinity, Maximum Observed Plasma Concentration [Cmax], Time to Reach Cmax)
时间窗: 0, 3, 8, and 17 minutes post-ingestion event time (IET) in Periods 1 and 2
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Acalabrutinib
时间窗: pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib
时间窗: pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
次要结局
- Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6h) of Acalabrutinib(pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2)
- Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) of Acalabrutinib(pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Acalabrutinib(pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2)
- Percent of AUC0-inf Extrapolated (AUC%extrap) of Acalabrutinib(pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2)
- Apparent Terminal Elimination Half-life (T1/2) of Acalabrutinib(pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2)
- Apparent Total Plasma Clearance (CL/F) of Acalabrutinib(pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2)
- Apparent Volume of Distribution (Vz/F) of Acalabrutinib(pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2)
- Incidences of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(Day 1 through 14 days after the last dose (approximately 1 month))
- Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs(Day 1 to Day 5 for each participant)
- Apparent Terminal Elimination Rate Constant (λz) of Acalabrutinib(pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2)
- Incidences of Abnormal Vital Signs and Physical Examinations Reported as TEAEs(Day 1 to Day 5 for each participant)
- Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs(Day 1 to Day 5 for each participant)