a drug-drug interaction study to assess the cyp1a2 and cyp3a4 interaction potential of tev-56286 (anle138b)

Conditions: Healthy Volunteers

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).

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

Keywords: anle138b (tev-56286) alpha-synuclein oligomer modulator multiple system atrophy parkinson disease alzheimer disease neurodegenerative diseases tauopathies amyloid drug-drug interaction