A Drug-Drug Interaction Study to Assess the CYP1A2 and CYP3A4 Interaction Potential of TEV-56286 (anle138b)

MODAG GmbH54 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Volunteers

Interventions

anle138b (TEV-56286)DRUG

Anle138b (TEV-56286) as perpetrator

Fluvoxamine 100 mg QD for 5 daysDRUG

Anle138b (TEV-56286) as victim

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Quotient Sciences

Nottingham, United Kingdom

Outcomes

Primary Outcomes

Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).

PK parameter: Cmax for caffeine.

Time frame: Day 1

Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).

PK parameter: AUC(0-inf) for caffeine.

Time frame: Day 1

Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).

PK parameter: AUC (0-last) for caffeine.

Time frame: Day 1

Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).

PK parameter: Cmax for midazolam.

Time frame: Day 1

Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).

PK parameter: AUC(0-inf) for midazolam.

Time frame: Day 1

Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).

PK parameter: AUC (0-last) for midazolam.

Time frame: Day 1

Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).

Cmax for caffeine.

Time frame: Day 3

Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).

Data from ClinicalTrials.gov

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Secondary Outcomes

Oral pharmacokinetics (PK) of substrates caffeine and midazolam

PK parameter: Tmax

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of substrates caffeine and midazolam

PK parameter: Tlag

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of substrates caffeine and midazolam

PK parameter: lambda-z

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of substrates caffeine and midazolam

PK parameter: T1/2

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of substrates caffeine and midazolam

PK parameter: CL/F

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of substrates caffeine and midazolam

PK parameter: Vz/F

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine

PK parameter: Tmax

Time frame: Day 19

Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine

PK parameter: lambda-z

Time frame: Day 19

Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine

PK parameter: T1/2

Time frame: Day 19

Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine

PK parameter: CL/F

Time frame: Day 19

Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine

PK parameter: Vz/F

Time frame: Day 19

Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam

PK parameter: Tmax

Time frame: Day 3

Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam

PK parameter: Cmax

Time frame: Day 3

Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam

PK parameter: AUC (0-last)

Time frame: Day 3

Oral pharmacokinetics (PK) of TEV-56286

PK parameter: Trough concentration for TEV-56286

Time frame: Day 3-18

Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam

PK parameter: Tmax

Time frame: Day 18

Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam

PK parameter: Cmax

Time frame: Day 18

Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam

PK parameter: Cmin

Time frame: Day 18

Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam

PK parameter: Cavg

Time frame: Day 18

Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam

PK parameter: AUC (0-tau)

Time frame: Day 18

Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam

PK parameter: AUC (0-last)

Time frame: Day 18

Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286

PK parameter: Tmax

Time frame: Day 19

Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286

PK parameter: Cmax

Time frame: Day 19

Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286

PK parameter: Cmin

Time frame: Day 19

Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286

PK parameter: Cavg

Time frame: Day 19

Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286

PK parameter: AUC (0-tau)

Time frame: Day 19

Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286

PK parameter: AUC (0-last)

Time frame: Day 19

Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286

PK parameter: Trough concentration for fluvoxamine

Time frame: Day 15-19

Oral pharmacokinetics (PK) of TEV-56286 after first dose administered as part of repeated administration

PK parameter: Tlag for TEV-56286

Time frame: Day 1

Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose

PK parameter: Tmax

Time frame: Day 1, Day 14

Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose

PK parameter: Cmax

Time frame: Day 1, Day 14

Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose

PK parameter: AUC (0-tau)

Time frame: Day 1, Day 14

Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose

PK parameter: lambda-z

Time frame: Day 1, Day 14

Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose

PK parameter: T1/2

Time frame: Day 1, Day 14

Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose

PK parameter: CL/F

Time frame: Day 1, Day 14

Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose

PK parameter: Vz/F

Time frame: Day 1, Day 14

Oral pharmacokinetics (PK) of TEV-56286 following multiple dose

PK parameter: AUC (0-last)

Time frame: Day 14

Oral pharmacokinetics (PK) of TEV-56286 following multiple dose

PK parameter: Cmin

Time frame: Day 14

Oral pharmacokinetics (PK) of TEV-56286 following multiple dose

PK parameter: Cavg

Time frame: Day 14

Oral pharmacokinetics (PK) of TEV-56286 following multiple dose

PK parameter: Accumulation ratio

Time frame: Day 14

Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam

PK parameter: Tmax

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam

PK parameter: Cmax

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam

PK parameter: AUC (0-last)

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam

PK parameter: AUC (0-inf)

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam

PK parameter: lambda-z

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam

PK parameter: T1/2

Time frame: Day 1, Day 3, Day 18

Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam

PK parameter: parent: metabolite ratio

Time frame: Day 1, Day 3, Day 18

Incidence of treatment-emergent adverse events including clinically significant changes in vital signs, ECGs and safety labs

adverse events and clinically significant changes in vital signs, ECGs and safety labs