Phase I, Open-label, Single Dose Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics (PK) of Evobrutinib (M2951) Compared to Normal Renal Function in Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Evobrutinib
研究概览
简要总结
The study will investigate the PK and safety of evobrutinib in subjects with different degree of renal impairment as compared to subjects with normal renal function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and Female subjects with total body weight between 50.0 and 100.0 kilograms(kg) (inclusive) and body mass index (BMI) between 19.0 and 36.0 kg per meter square (inclusive) at the time of the screening examination
- •For subjects with impaired renal function: Subjects must have an eGFR according to the Modification of diet in renal disease (MDRD) equation of less than 90 mL per minute at screening and the possibility of stratification to one of the groups and a stable renal function as defined by either: if the time interval between screening and dosing is greater than 10 days, two eGFR with the second estimate within 20% of prior value or historical records of stable function over the past 3 months if within 20 percentage of screening value and within 10 days of dosing
- •Other protocol defined inclusion criteria could apply
排除标准
- •History or presence of respiratory, gastrointestinal (including bariatric or other gastric surgeries, or other conditions that may affect drug absorption) hepatic (including hepatorenal syndrome), hematological, lymphatic, neurological (including seizures), cardiovascular (including ventricular dysfunction and congestive heart failure), psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders that may affect the safety of the subject.
- •Clinical history of any autoimmune disorder
- •Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to Screening, which might interfere with the objectives of the study or the study procedures
- •History of any malignancy except superficial basal cell carcinoma treated for curative intent may be allowed
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Evobrutinib: Normal Renal Function
Subjects with estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 90 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) will receive a single oral dose of evobrutinib under fasting conditions.
干预措施: Evobrutinib (Drug)
Evobrutinib: Severe Renal Impairment
Subjects with eGFR less than (<) 30 mL/min/1.73 m^2 will receive a single oral dose of evobrutinib under fasting conditions.
干预措施: Evobrutinib (Drug)
Evobrutinib: Moderate Renal Impairment
Subjects with eGFR >= to 30 mL/min/1.73 m^2 and < 60 mL/min/1.73 m^2 will receive a single oral dose of evobrutinib under fasting conditions.
干预措施: Evobrutinib (Drug)
Evobrutinib: Mild Renal Impairment
Subjects with eGFR >= to 60 mL/min/1.73 m^2 and < 90 mL/min/1.73 m^2 will receive a single oral dose of evobrutinib under fasting conditions.
干预措施: Evobrutinib (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Evobrutinib
时间窗: Pre-dose up to 30 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib
时间窗: Pre-dose up to 30 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
时间窗: Pre-dose up to 30 hours post-dose
次要结局
- Number of Subjects With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings(Day 1 up to Day 6)
- Time to Reach the Maximum Plasma Concentration (tmax) of Evobrutinib(Pre-dose up to 30 hours post-dose)
- Time Prior to the First Measurable (Non-Zero) Concentration (t lag) of Evobrutinib(Pre-dose up to 30 hours post-dose)
- Amount of Unchanged Drug (Evobrutinib) Excreted in Urine During Collection Interval (0-8 hours) (Ae0-8h)(Pre-dose up to 8 hours post-dose)
- Renal Clearance of Evobrutinib (CLR)(Pre-dose up to 30 hours post-dose)
- Non-Renal Clearance of Evobrutinib (CLNonR/f)(Pre-dose up to 30 hours post-dose)
- Terminal Rate Constant (λz) of Evobrutinib(Pre-dose up to 30 hours post-dose)
- Terminal Half-Life (t1/2) of Evobrutinib(Pre-dose up to 30 hours post-dose)
- Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours After Dosing (AUC 0-8h) of Evobrutinib(Pre-dose up to 8 hours post-dose)
- Occurrences of Treatment-emergent Adverse Events (TEAEs)(Day 1 up to Day 6)
- Number of Subjects With TEAEs According to Severity(Day 1 up to Day 6)
- Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours After Dosing (AUC 0-24h) of Evobrutinib(Pre-dose up to 24 hours post-dose)
- Apparent Volume of Distribution During Terminal Phase (Vz/f) of Evobrutinib(Pre-dose up to 30 hours post-dose)
- Fraction of Administered Drug (Evobrutinib) Excreted in Urine (fe)(Pre-dose up to 30 hours post-dose)
- Fraction of Unbound Drug (Evobrutinib) in the Plasma (fu)(Pre-dose up to 30 hours post-dose)
- Apparent Clearance (CL/f) of Evobrutinib(Pre-dose up to 30 hours post-dose)