A Drug-Drug Interaction Study to Assess the CYP1A2 and CYP3A4 Interaction Potential of TEV-56286 (anle138b)
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Drug: anle138b (TEV-56286)
- Registration Number
- NCT05532358
- Lead Sponsor
- MODAG GmbH
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
Inclusion Criteria
- 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/m2.
- Must agree to adhere to the contraception requirements defined in the study protocol.
Exclusion Criteria
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description anle138b (TEV-56286) as perpetrator (part I) anle138b (TEV-56286) Drug: TEV-56286 300 mg QD (single dose and multiple dose for 14 days) Victim drugs: Caffeine 200 mg Midazolam 2 mg anle138b (TEV-56286) as victim (part II) Fluvoxamine 100 mg QD for 5 days 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
- Primary Outcome Measures
Name Time Method Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I). 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). 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). 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). 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). 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). 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). 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. Day 19 PK parameter: AUC(0-tau) for TEV-56286 (Part II).
- Secondary Outcome Measures
Name Time Method Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam Day 18 PK parameter: AUC (0-last)
Number of participants reporting use of concomitant medications Day 1 up to follow up visit (5-11 days post last TEV-56286 dose) Number of participants reporting use of concomitant medications
Oral pharmacokinetics (PK) of TEV-56286 after first dose administered as part of repeated administration Day 1 PK parameter: Tlag for TEV-56286
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose Day 14 PK parameter: Accumulation ratio
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine Day 19 PK parameter: Vz/F
Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam Day 3 PK parameter: AUC (0-last)
Oral pharmacokinetics (PK) of TEV-56286 Day 3-18 PK parameter: Trough concentration for TEV-56286
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286 Day 15-19 PK parameter: Trough concentration for fluvoxamine
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose Day 1, Day 14 PK parameter: Vz/F
Oral pharmacokinetics (PK) of substrates caffeine and midazolam Day 1, Day 3, Day 18 PK parameter: Vz/F
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) adverse events and clinically significant changes in vital signs, ECGs and safety labs
Columbia-Suicide Severity Rating Scale (C-SSRS) total score Day 3 to day 21 Columbia-Suicide Severity Rating Scale (C-SSRS) total score
Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam Day 1, Day 3, Day 18 PK parameter: parent: metabolite ratio
Trial Locations
- Locations (1)
Quotient Sciences
🇬🇧Nottingham, United Kingdom