Clinical trial NCT05532358: A Drug-Drug Interaction Study to Assess the CYP1A2 and CYP3A4 Interaction Potential of TEV-56286 (anle138b)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: anle138b (TEV-56286)
alpha-Synuclein
Oligomer modulator
Multiple System Atrophy
Parkinson Disease
Alzheimer Disease
Neurodegenerative diseases
Tauopathies
Amyloid
Drug-drug interaction
Lead sponsor: MODAG GmbH
Sponsor class: INDUSTRY
Collaborators: name: Aptuit
name: Quotient Sciences
name: Teva Pharmaceutical Industries, Ltd.
First posted: 2022-09-08
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Drug drug interaction study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 1
measure: Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 1
measure: Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 1
measure: Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 1
measure: Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 1
measure: Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 1
measure: Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of midazolam after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of midazolam after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of midazolam after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of caffeine after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of caffeine after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of caffeine after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of TEV-56286 without fluvoxamine in healthy volunteers after repeated administration in the fasted state (Part II).
timeFrame: Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 without fluvoxamine in healthy volunteers after repeated administration in the fasted state (Part II).
timeFrame: Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 in healthy volunteers after repeated co-administration with fluvoxamine in the fasted state.
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of TEV-56286 in healthy volunteers after repeated co-administration with fluvoxamine in the fasted state.
timeFrame: Day 19
Secondary outcomes:
measure: Oral pharmacokinetics (PK) of substrates caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of substrates caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of substrates caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of substrates caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of substrates caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of substrates caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
timeFrame: Day 3
measure: Oral pharmacokinetics (PK) of TEV-56286
timeFrame: Day 3-18
measure: Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
timeFrame: Day 18
measure: Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
timeFrame: Day 19
measure: Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
timeFrame: Day 15-19
measure: Oral pharmacokinetics (PK) of TEV-56286 after first dose administered as part of repeated administration
timeFrame: Day 1
measure: Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
timeFrame: Day 1, Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
timeFrame: Day 1, Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
timeFrame: Day 1, Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
timeFrame: Day 1, Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
timeFrame: Day 1, Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
timeFrame: Day 1, Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
timeFrame: Day 1, Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
timeFrame: Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
timeFrame: Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
timeFrame: Day 14
measure: Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
timeFrame: Day 14
measure: Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam
timeFrame: Day 1, Day 3, Day 18
measure: Incidence of treatment-emergent adverse events including clinically significant changes in vital signs, ECGs and safety labs
timeFrame: Day 1 up to follow up visit (5-11 days post last TEV-56286 dose)
measure: Number of participants reporting use of concomitant medications
timeFrame: Day 1 up to follow up visit (5-11 days post last TEV-56286 dose)
measure: Columbia-Suicide Severity Rating Scale (C-SSRS) total score
timeFrame: Day 3 to day 21
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Sciences
Study officials:
affiliation: Quotient Sciences Mere Way Ruddington Fields Ruddington Nottingham NG11 6JS, UK
name: Nand Singh, MD
role: PRINCIPAL_INVESTIGATOR
References:
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