Healthy Volunteers
Conditions
Keywords
anle138b (TEV-56286), alpha-Synuclein, Oligomer modulator, Multiple System Atrophy, Parkinson Disease, Alzheimer Disease, Neurodegenerative diseases, Tauopathies, Amyloid, Drug-drug interaction
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.
Interventions
DRUGanle138b (TEV-56286)
Anle138b (TEV-56286) as perpetrator
DRUGFluvoxamine 100 mg QD for 5 days
Anle138b (TEV-56286) as victim
Sponsors
Aptuit
Quotient Sciences
Teva Pharmaceutical Industries, Ltd.
MODAG GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Drug drug interaction study
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I). | Day 1 | PK parameter: Cmax for caffeine. |
| Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I). | Day 1 | PK parameter: Cmax for midazolam. |
| Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I). | Day 3 | Cmax for caffeine. |
| Oral pharmacokinetics (PK) of midazolam after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I). | Day 3 | Cmax for midazolam |
| Oral pharmacokinetics (PK) of caffeine after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I). | Day 18 | PK parameter: Cmax for caffeine. |
| Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I). | Day 18 | PK parameter: Cmax 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: Cmax for TEV-56286. |
| Oral pharmacokinetics (PK) of TEV-56286 in healthy volunteers after repeated co-administration with fluvoxamine in the fasted state. | Day 19 | PK parameter: Cmax for TEV-56286 (Part II). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oral pharmacokinetics (PK) of TEV-56286 following multiple dose | Day 14 | PK parameter: AUC (0-last) |
| 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: Tmax |
| Oral pharmacokinetics (PK) of substrates caffeine and midazolam | Day 1, Day 3, Day 18 | PK parameter: Tmax |
| 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 |
| Columbia-Suicide Severity Rating Scale (C-SSRS) total score | Day 3 to day 21 | Columbia-Suicide Severity Rating Scale (C-SSRS) total score |
| 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 |
| Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine | Day 19 | PK parameter: Tmax |
| Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam | Day 3 | PK parameter: Tmax |
| Oral pharmacokinetics (PK) of TEV-56286 | Day 3-18 | PK parameter: Trough concentration for TEV-56286 |
| Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam | Day 18 | PK parameter: Tmax |
| Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286 | Day 19 | PK parameter: Tmax |
| 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 single dose and multiple dose | Day 1, Day 14 | PK parameter: Tmax |
Countries
United Kingdom
Outcome results
None listed