NCT05248945已完成1 期
Phase I, Open-Label, Single-Sequence Study of the Effect of Multiple Doses of Carbamazepine on Single-Dose Evobrutinib Pharmacokinetics in Healthy Participants
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany1 个研究点 分布在 1 个国家目标入组 14 人开始时间: 2022年1月13日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib
研究概览
简要总结
The purpose of this study was to investigate the effect of multiple doses of carbamazepine on two single doses of evobrutinib pharmacokinetics (PK) in healthy participants. Study details included:
Study Duration: up to 54 days. Treatment Duration: 25 days. Visit Frequency: Participants were residents in the Clinical Research Unit from Day 1 to Day 20 and returned on Day 26 for a Safety Follow-Up visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Type of Participant and Disease Characteristics
- •Had a body weight within 50.0 and 100.0 kg (kilogram) (inclusive) and Body Mass Index (BMI) within the range 19.0 and 30.0 kilogram per meter square (kg/m^2) (inclusive)
- •Male: No contraception and barrier requirements were needed. Female: Was not a woman of childbearing potential
- •Were capable of giving signed informed consent, which included compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol
- •Were stable nonsmokers for at least 3 months preceding Screening
排除标准
- •Had a history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, musculoskeletal, genitourinary, immunological, dermatological, connective tissue, psychiatric (due to rare risk of hallucinations, agitation and activation of psychosis), and other diseases or disorders, and epilepsy, as determined by medical evaluation
- •Had been administered live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines (e.g., SARSCoV2 vaccines) was allowed until 2 weeks before admission to Clinical Research Unit (CRU), thereafter it was prohibited until the end of the study
- •Had been administered moderate or strong inhibitors or inducers of Cytochrome P450 (CYP)3A4/5 or Pgp within 4 weeks prior to the first administration of study intervention
- •Had a contraindication to carbamazepine (carbamazepine SmPC)
- •Had a history of any malignancy
- •Had a history of drug hypersensitivity ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other hypersensitivity reaction in general, including contact hypersensitivity to Electrocardiogram (ECG) electrodes, which may have affected the safety of the participant and/or outcome of the study per the Investigator's discretion.
- •Other protocol defined exclusion criteria could have applied.
研究组 & 干预措施
Evobrutinib plus Carbamazepine
Experimental
干预措施: Evobrutinib (Drug)
Evobrutinib plus Carbamazepine
Experimental
干预措施: Carbamazepine (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib
时间窗: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
时间窗: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 16 and 24 hours post dose on Day 1 and Day 19.
Cmax was obtained from plasma concentration time curve.
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Serious TEAEs(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, and Lymphocytes Values(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Hematology Parameter: Hemoglobin Levels(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Hematology Parameter: Hematocrit Values(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Hematology Parameter: Activated Partial Thromboplastin Time(Baseline (Day 1) and Day 26)
- Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/ Leukocytes, and Neutrophils/Leukocytes(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Biochemistry Parameter: Bilirubin, Creatinine and Urate(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Biochemistry Parameter: Sodium, Potassium, Calcium, Magnesium and Phosphate Levels(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Biochemistry Parameter: Protein and Albumin Levels(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase, Amylase, Lipase, Creatinine Kinase, Gamma Glutamyl Transferase Levels, Lactate Dehydrogenase, Aspartate Aminotransferase(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Biochemistry Parameter: Glucose, Chloride, Cholesterol, Triglycerides, Phosphate Levels(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in 12-Lead ECG Parameter: Heart Rate(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in 12-Lead ECG Parameter: RR Duration, QT Duration, Fridericia's Formula (QTcF), PR Duration and QRS Duration(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Vital Sign: Blood Pressure(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Vital Sign: Pulse Rate(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Vital Sign: Respiratory Rate(Baseline (Day 1) and Day 26)
- Absolute Change From Baseline in Vital Sign: Body Temperature(Baseline Day 1 and Day 26)
- Total Body Clearance of Evobrutinib From Plasma (CL/f)(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.)
- Apparent Volume of Distribution (Vz/f) of Evobrutinib(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.)
- Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Evobrutinib(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.)
- Time to Reach the Maximum Plasma Concentration (Tmax) of Evobrutinib(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.)
- Apparent Terminal Half-Life (t1/2) of Evobrutinib in Plasma(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Evobrutinib Metabolite (MSC2729909A)(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.)
- Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (LOQ) (AUC0-tlast) of Evobrutinib Metabolite (MSC2729909A)(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.)
- Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Metabolite (MSC2729909A)(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.)
- Time to Reach the Maximum Plasma Concentration (Tmax) of Evobrutinib Metabolite (MSC2729909A)(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.)
- Time Prior to the First Quantifiable (Non-zero) Concentration (Tlag) of Evobrutinib Metabolite (MSC2729909A) in Plasma(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.)
- Metabolite to Parent Ratios for Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Evobrutinib Metabolite (MSC2729909A)(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.)
- Metabolite to Parent Ratios for Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Metabolite (MSC2729909A)(Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity(Baseline (Day 1) and Day 26)
研究者
研究点 (1)
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