An Open-Label, One-Sequence, Two-Part Drug-Drug Interaction Study in Healthy Volunteers to Assess the CYP1A2 and CYP3A4 Perpetrator Interaction Potential and CYP1A2 Victim Potential of TEV-56286 (anle138b)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MODAG GmbH
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
研究概览
简要总结
The purpose of this healthy volunteers drug-drug interaction study is to assess the CYP1A2 and CYP3A4 perpetrator interaction potential and CYP1A2 victim potential of TEV-56286 (anle138b).
详细描述
This a 2-part DDI study that will assess the CYP1A2 and CYP3A4 perpetrator interaction potential of TEV-56286 single dose and multiple dose, using caffeine and midazolam as substrates and CYP1A2 victim potential of TEV-56286 (anle138b) at steady state induction using fluvoxamine as inhibitor [1,2].The estimated time from screening until the follow-up visit is approximately up to 8 weeks for each subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males or healthy females of non-childbearing potential
- •Must provide written informed consent for participation in the study and must be able to understand the study requirements
- •Body mass index (BMI) 18.5 to 32.0 kg/m
- •Must agree to adhere to the contraception requirements defined in the study protocol.
排除标准
- •Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients e.g. fluvoxamine, caffeine, midazolam or benzodiazepines or any of its excipients, or a known drug hypersensitivity idiosyncratic reaction to TEV-56286, or one of its excipients
- •History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, metabolic diseases or a history of any illness that, in the opinion of the investigator, might pose additional risk to the subject by participation in the study or confound the results of the study
- •Acute infection and/or antibiotic treatment within 28 days of Day 1
- •Major trauma or surgery in the 2 months before screening or at any time between screening and Day 1, or surgery scheduled during the study or follow up period
- •History of malignancy or treatment of malignancy in the last 5 years
- •History of suicidal ideation with an intent and/or plan and behaviour based upon either clinical history or source documents
- •Personal or family history of arrhythmia, sudden unexplained death at a young age (before 40 years) in a first-degree relative, or long QT syndrome, or a personal history of syncope or previous treatment for high blood pressure (BP). Abnormality of 12-lead ECG that may, in the opinion of the investigator, interfere with study participation
- •Any procedure or disorder that may interfere with drug absorption, distribution, metabolism, or excretion
- •Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator.
- •Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer
- •Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies in the 14 days before study medication administration or within 5 half-lives whichever is longer.
- •Subjects who are taking, or have taken hormonal contraceptives (e.g., oral, patch, injectable or intrauterine device) hormone replacement therapy (HRT) or a long-acting injectable hormonal within 4 weeks prior to first dose of IMP
- •Subjects who are taking, or have taken any inducer of CYP 1A2, CYP3A4 within 28 days prior to Day -2
- •History of any drug or alcohol abuse in the past 2 years
- •Current smokers and those who have smoked within the last 12 months or has a positive urine cotinine test
- •Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
- •Subjects with a previous history of difficulty in swallowing tablets or capsules, or an anticipated problem with swallowing a large number of capsules
- •Subjects who have consumed grapefruit, grapefruit juice, Seville oranges, pomelo-containing products, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, brussel sprouts, and mustard) and charbroiled meats within the 14 days prior to Day -2
- •Subjects who are unwilling to comply with the restricted use of caffeinated beverages (e.g. coffee, tea, cola) during the study
研究组 & 干预措施
anle138b (TEV-56286) as perpetrator (part I)
Drug: TEV-56286 300 mg QD (single dose and multiple dose for 14 days)
Victim drugs:
Caffeine 200 mg Midazolam 2 mg
干预措施: anle138b (TEV-56286) (Drug)
anle138b (TEV-56286) as victim (part II)
Drug: fluvoxamine 100 mg QD for 5 days
Victim drug:
TEV-56286 150 mg QD for 14 days + 5 days of co-administation with fluvoxamine
干预措施: Fluvoxamine 100 mg QD for 5 days (Drug)
结局指标
主要结局
Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
时间窗: Day 18
PK parameter: AUC (0-last) for midazolam.
Oral pharmacokinetics (PK) of TEV-56286 without fluvoxamine in healthy volunteers after repeated administration in the fasted state (Part II).
时间窗: Day 14
PK parameter: AUC(0-tau) for TEV-56286.
Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
时间窗: Day 3
PK parameter: AUC (0-last) for caffeine.
Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
时间窗: Day 1
PK parameter: AUC (0-last) for caffeine.
Oral pharmacokinetics (PK) of caffeine after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
时间窗: Day 18
PK parameter: AUC (0-last) for caffeine.
Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
时间窗: Day 1
PK parameter: AUC (0-last) for midazolam.
Oral pharmacokinetics (PK) of midazolam after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
时间窗: Day 3
PK parameter: AUC (0-last) for midazolam.
Oral pharmacokinetics (PK) of TEV-56286 in healthy volunteers after repeated co-administration with fluvoxamine in the fasted state.
时间窗: Day 19
PK parameter: AUC(0-tau) for TEV-56286 (Part II).
次要结局
- Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam(Day 18)
- Oral pharmacokinetics (PK) of TEV-56286 after first dose administered as part of repeated administration(Day 1)
- Oral pharmacokinetics (PK) of TEV-56286 following multiple dose(Day 14)
- Number of participants reporting use of concomitant medications(Day 1 up to follow up visit (5-11 days post last TEV-56286 dose))
- Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine(Day 19)
- Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam(Day 3)
- Oral pharmacokinetics (PK) of TEV-56286(Day 3-18)
- Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286(Day 15-19)
- Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose(Day 1, Day 14)
- Oral pharmacokinetics (PK) of substrates caffeine and midazolam(Day 1, Day 3, Day 18)
- Incidence of treatment-emergent adverse events including clinically significant changes in vital signs, ECGs and safety labs(Day 1 up to follow up visit (5-11 days post last TEV-56286 dose))
- Columbia-Suicide Severity Rating Scale (C-SSRS) total score(Day 3 to day 21)
- Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam(Day 1, Day 3, Day 18)