A Single-Dose, Randomized, Double-Blind, Placebo- and Positive-Controlled, 4-Way Crossover Study to Evaluate the Effect of Evobrutinib on the QTc (Corrected QT) Interval in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Evobrutinib
研究概览
简要总结
The purpose of this study is to assess potential effects of M2951 on cardiac repolarization (i.e. prolongation of QT interval).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Participants are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection, or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
- •Participants have a body weight within 50.0 and 100.0 kilograms (kg) (inclusive) and body mass index (BMI) within the range 19.0 and 30.0 kilograms per square meter (kg/m^2) (inclusive)
- •Participants are stable nonsmokers for at least 3 months preceding the first administration of study intervention
排除标准
- •Participants with 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
- •Participants with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease will be excluded from the study. Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to the first administration of study intervention
- •Participants with history of any malignancy
- •Participants with history of seizures
- •Participants with history of pharmacologically treated psychiatric disease
研究组 & 干预措施
Treatment Sequence 1
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: Placebo matched to M2951 (Drug)
Treatment Sequence 1
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 1
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: M2951 Low Dose (Drug)
Treatment Sequence 1
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: M2951 High Dose (Drug)
Treatment Sequence 2
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: Placebo matched to M2951 (Drug)
Treatment Sequence 2
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 2
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: M2951 Low Dose (Drug)
Treatment Sequence 2
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: M2951 High Dose (Drug)
Treatment Sequence 3
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: Placebo matched to M2951 (Drug)
Treatment Sequence 3
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 3
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: M2951 Low Dose (Drug)
Treatment Sequence 3
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: M2951 High Dose (Drug)
Treatment Sequence 4
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: Placebo matched to M2951 (Drug)
Treatment Sequence 4
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: Moxifloxacin (Drug)
Treatment Sequence 4
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: M2951 Low Dose (Drug)
Treatment Sequence 4
Participants will receive one of the four interventions in a sequence decided at randomization.
干预措施: M2951 High Dose (Drug)
结局指标
主要结局
Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Evobrutinib
时间窗: Baseline and from 1 hour before any administration until 24 hours post-administration at the following timepoints: -1-hour, 5 min, 10 min, 20 min, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours
A linear mixed-effects model was used to analyze the relationship between evobrutinib and MSC2729909A concentrations and ΔQTc. Based on this model, drug-induced ΔΔQTc and its two-sided 90% CI was predicted over the clinical concentration range and at concentrations corresponding to the observed geometric mean Cmax following administration of 45 mg and 225 mg evobrutinib. The higher geometric mean Cmax calculated based on the PK and ECG Analysis Sets was considered.
次要结局
- Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Moxifloxacin(From 1 hour before any administration until 24 hours post-administration at the following timepoints: -1-hour, 5 min, 10 min, 20 min, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Up to 3 months)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity(Up to 3 months)
- Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests(Up to Day 29)
- Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs(Up to Day 29)
- Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings(Up to Day 29)
- Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) of Evobrutinib(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Maximum Observed Plasma Concentration (Cmax) of Evobrutinib(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Time to Reach Maximum Blood Concentration (Tmax) of Evobrutinib(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Apparent Terminal Half-life (t1/2) of Evobrutinib(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) Of Moxifloxacin(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Moxifloxacin(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Time to Reach Maximum Blood Concentration (Tmax) of Moxifloxacin(Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22)
- Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate(Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours)
- Effect of Evobrutinib on ECG Parameters: RR Interval(Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours)
- Effect of Evobrutinib on ECG Parameters: QT Interval(Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours)
- Effect of Evobrutinib on ECG Parameters: QTcF Interval(Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours)
- Effect of Evobrutinib on ECG Parameters: QTcP Interval(Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours)
- Effect of Evobrutinib on ECG Parameters: PR Interval(Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours)
- Effect of Evobrutinib on ECG Parameters: QRS Duration(Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours)