A 3-way, Crossover, Randomized, Open-label Study in Healthy Subjects Comparing the Bioavailability of Belumosudil (KD025) Tablets in Fed and Fasted States and Relative Bioavailability of Tablets and Capsules in the Fed State
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
研究概览
简要总结
Phase 1 bioavailability study to evaluate the pharmacokinetics (PK) and tolerability/safety of the belumosudil tablet formulation in the fasted and fed states and compared to the belumosudil capsule formulation in the fed state.
详细描述
This is a Phase 1, 3-way, crossover, randomized, open-label study in healthy subjects designed to compare the bioavailability of belumosudil (previously known as KD025) tablet formulation administered in the fed and fasted states and to assess the relative bioavailability of belumosudil tablet and capsule formulations in the fed state.
The primary objective of the study is to determine the PK parameters of belumosudil tablet formulation in the fed and fasted states.
The secondary objectives of the study are: (1) to assess the relative bioavailability of a tablet (test) to capsule (reference formulation of belumosudil; (2) to assess and compare the variability in the maximum concentration (Cmax) and area under the concentration-time curve (AUC) for belumosudil treatments (belumosudil 200 mg tablet in the fasting state, belumosudil 200 mg tablet in the fed state, and belumosudil as two 100 mg capsules in the fed state); and (3) to provide additional safety and tolerability information for belumosudil.
This is a single-center, open-label, randomized, single-dose, 3-period, 3-way, crossover study in healthy subjects.
In each of 3 study periods, each subject receives 1 of the following single-dose treatments:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •To be eligible for study entry subjects has to satisfy all of the following criteria:
- •Healthy males
- •Aged 18 to 55 years of age
- •Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination), ECG, and laboratory investigations (hematology, coagulation, clinical chemistry and urinalysis)
- •Body mass index 18.0-30.0 kg/m^2, or if outside the range, considered not clinically significant by the Investigator
- •Willing and able to communicate and participate in the whole study
- •Provide written informed consent
- •Agree to use an adequate method of contraception for up to 90 days post discharge
- •Exclusion Criteria
- •Subjects are excluded from the study if one of more of the following statements is applicable:
- •Participated in a clinical research study within the previous 3 months
- •Study site employees, or immediate family members of a study site or sponsor employee
- •Had been previously enrolled in this study
- •History of any drug or alcohol abuse in the past 2 years
- •Regular alcohol consumption > 21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
- •Current smokers and those who had smoked within the last 12 months. A breath carbon monoxide (CO) reading of greater than 10 ppm at screening
- •Did not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator at screening
- •Clinically significant abnormal biochemistry, hematology, coagulation, or urinalysis as judged by the Investigator
- •Positive drugs of abuse test result or alcohol breath test
- •Positive hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) or human immunodeficiency virus (HIV) results
- •History of any clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal (GI) disease that may have compromised the subject's safety or interfered with the objectives of the study as judged by the investigator
- •Subject had a history or presence of any of the following:
- •Active GI disease requiring therapy
- •Hepatic disease and/or alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) > 1.5 × upper limit of normal (ULN) at screening
- •Renal disease and/or serum creatinine > 1.5 × ULN at screening
- •Other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs
- •QT interval corrected using Fridericia's formula (QTcF) > 450 msec at the screening or admission ECG
- •Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
- •Known sensitivity to ROCK2 inhibitor agents or to any of the constituents of the belumosudil formulation
- •Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator. Hayfever is permitted unless it is active.
- •Donation or loss of > 400 mL of blood within the previous 3 months
- •Taking or had taken any prescribed or over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies in the 14 days before IP administration
- •Fails to satisfy the Investigator's discretion of fitness to participate or for any other reason
- •Additional Restrictions
- •Abstain from alcohol during the 24 h prior to each admission until discharge from the clinic in each study period
- •Not to drink liquids or eat food containing grapefruit, cranberry, caffeine, or other xanthines from 24 hours prior to each admission until 48 hours post-dose
- •Refrain from eating food containing any seeds (e.g., poppy) for 48 hours before the screening visit and then from 48 h prior to each admission until discharge from the clinic for each study period
- •Not to take part in any unaccustomed strenuous exercise from 72 hours prior to the screening visit and then from 72 hours prior to admission until discharge from the study
排除标准
- 未提供
研究组 & 干预措施
Regimen A
Single-dose belumosudil 200 mg tablet in the fasted state
干预措施: Belumosudil Tablet (Drug)
Regimen B
Single-dose belumosudil 200 mg tablet in the fed state
干预措施: Belumosudil Tablet (Drug)
Regimen C
Single-dose belumosudil capsules (administered as two 100-mg capsules) in the fed state
干预措施: Belumosudil Capsule (Drug)
结局指标
主要结局
Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
时间窗: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Maximum concentration (Cmax) of parent drug (KD025), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) at 48 hours after dosing
Pharmacokinetics: AUCs of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose
时间窗: Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose
Area under concentration-time curve from zero to last dose of belumosudil 200 mg tablets (AUC\[0-last\]) and from zero to infinity (AUC\[0-inf\]) for Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) when administering a single dose of belumosudil 200 mg tablet to subjects who are fasting (Regimen A) compared to administering a single dose of belumosudil 200 mg tablet to subjects who are fed (Regimen B) at 48 hours after dosing
次要结局
- Pharmacokinetics: AUCs for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose(Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose)
- Safety: Number of Subjects With TEAEs and SAEs(Approximately 1 month)
- Pharmacokinetics: Lambda-z for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose(Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose)
- Safety: Total Number of Participants With TEAEs, Related TEAEs, Leading to Withdrawal, Severe, Serious, Leading to Death(Approximately 1 month)
- Pharmacokinetics: Cmax of Dosing Regimen A (Tablets--Fasting) vs. Dosing Regimen B (Tablets--Fed) vs. Dosing Regimen C (Capsules--Fed) for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose(Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose)
- Pharmacokinetics: AUCs of Regimen A (Tablet--Fasting) vs. Dosing Regimen B (Tablet--Fed) vs. Dosing Regimen C (Capsule--Fed) for KD025, KD025m1, and KD025m2 for Belumosudil 200 mg at 48 Hours Post-dose(Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose)
- Pharmacokinetics: Cmax for the Relative Bioavailability of Regimen B/Regimen A and Regimen B/Regimen C by Ratio of the Adjusted Geometric Means at 48 Hours Post-dose(Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose)
- Pharmacokinetics: t(1/2), MRT(0-last), and MRT(0-inf) for Regimens A, B, and C for KD025, KD025m1, and KD025m2 at 48 Hours Post-dose(Pre-dose (0), and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours post-dose)