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

NCT05532358 | Completed Phase 1

• 2 other identifiers: anle138b-P1-032022-002467-30
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

Primary Outcomes (22)

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

  PK parameter: Cmax for caffeine.

  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.

  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.

  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.

  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.

  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.

  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.

  Day 3

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

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

  Day 3

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

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

  Day 3

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

  Cmax for midazolam

  Day 3

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

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

  Day 3

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

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

  Day 3

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

  PK parameter: Cmax for caffeine.

  Day 18

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

  AUC(0-inf) for caffeine.

  Day 18

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

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

  Day 18

• Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).

  PK parameter: Cmax for midazolam.

  Day 18

• Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).

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

  Day 18

• Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).

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

  Day 18

• Oral pharmacokinetics (PK) of TEV-56286 without fluvoxamine in healthy volunteers after repeated administration in the fasted state (Part II).

  PK parameter: Cmax for TEV-56286.

  Day 14

• Oral pharmacokinetics (PK) of TEV-56286 without fluvoxamine in healthy volunteers after repeated administration in the fasted state (Part II).

  PK parameter: AUC(0-tau) for TEV-56286.

  Day 14

• Oral pharmacokinetics (PK) of TEV-56286 in healthy volunteers after repeated co-administration with fluvoxamine in the fasted state.

  PK parameter: Cmax for TEV-56286 (Part II).

  Day 19

• Oral pharmacokinetics (PK) of TEV-56286 in healthy volunteers after repeated co-administration with fluvoxamine in the fasted state.

  PK parameter: AUC(0-tau) for TEV-56286 (Part II).

  Day 19

Secondary Outcomes (50)

• Oral pharmacokinetics (PK) of substrates caffeine and midazolam

  Day 1, Day 3, Day 18

• Oral pharmacokinetics (PK) of substrates caffeine and midazolam

  Day 1, Day 3, Day 18

• Oral pharmacokinetics (PK) of substrates caffeine and midazolam

  Day 1, Day 3, Day 18

• Oral pharmacokinetics (PK) of substrates caffeine and midazolam

  Day 1, Day 3, Day 18

• Oral pharmacokinetics (PK) of substrates caffeine and midazolam

  Day 1, Day 3, Day 18

Study Arms (2)

anle138b (TEV-56286) as perpetrator (part I)

EXPERIMENTAL

Drug: TEV-56286 300 mg QD (single dose and multiple dose for 14 days) Victim drugs: Caffeine 200 mg Midazolam 2 mg

Drug: anle138b (TEV-56286)

anle138b (TEV-56286) as victim (part II)

EXPERIMENTAL

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

Drug: Fluvoxamine 100 mg QD for 5 days

Interventions

anle138b (TEV-56286) DRUG

Anle138b (TEV-56286) as perpetrator

Also known as: Caffeine, Midazolam, Fluvoxamine

anle138b (TEV-56286) as perpetrator (part I)

Fluvoxamine 100 mg QD for 5 days DRUG

Anle138b (TEV-56286) as victim

Also known as: TEV-56286 150 mg QD for 14 days + 5 days of co-administation with fluvoxamine

anle138b (TEV-56286) as victim (part II)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• MODAG GmbH: lead
• Aptuit: collaborator
• Quotient Sciences: collaborator
• Teva Pharmaceutical Industries, Ltd.: collaborator

Study Sites (1)

Quotient Sciences

Nottingham, NG11 6JS, United Kingdom

Location

Related Publications (4)

• Levin J, Sing N, Melbourne S, Morgan A, Mariner C, Spillantini MG, Wegrzynowicz M, Dalley JW, Langer S, Ryazanov S, Leonov A, Griesinger C, Schmidt F, Weckbecker D, Prager K, Matthias T, Giese A. Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: A randomised, double-blind, placebo-controlled phase 1a trial. EBioMedicine. 2022 Jun;80:104021. doi: 10.1016/j.ebiom.2022.104021. Epub 2022 Apr 29.

  PMID: 35500536 BACKGROUND

• Wagner J, Ryazanov S, Leonov A, Levin J, Shi S, Schmidt F, Prix C, Pan-Montojo F, Bertsch U, Mitteregger-Kretzschmar G, Geissen M, Eiden M, Leidel F, Hirschberger T, Deeg AA, Krauth JJ, Zinth W, Tavan P, Pilger J, Zweckstetter M, Frank T, Bahr M, Weishaupt JH, Uhr M, Urlaub H, Teichmann U, Samwer M, Botzel K, Groschup M, Kretzschmar H, Griesinger C, Giese A. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease. Acta Neuropathol. 2013 Jun;125(6):795-813. doi: 10.1007/s00401-013-1114-9. Epub 2013 Apr 19.

  PMID: 23604588 BACKGROUND

• Drug Interaction Studies M12. ICH Harmonised Guideline. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Draft version endorsed on 24 May 2022.

  BACKGROUND

• Clinical Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry. US Food and Drug Administration. 07 Jul 2020. Available online: https://www.fda.gov/regulatoryinformation/search-fda-guidance-documents/clinical-drug-interaction-studiescytochrome-p450-enzyme-and-transporter-mediated-drug-interactions (accessed 23 Jun 2022).

  BACKGROUND

Related Links

• Description Sponsor Homepage

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body; Multiple System Atrophy; Parkinson Disease; Alzheimer Disease; Neurodegenerative Diseases; Tauopathies

Interventions

3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole; Caffeine; Midazolam; Fluvoxamine

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Parkinsonian Disorders; Dementia; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines; Oximes; Hydroxylamines; Amines; Organic Chemicals

Study Officials

• Nand Singh, MD

  Quotient Sciences Mere Way Ruddington Fields Ruddington Nottingham NG11 6JS, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Drug drug interaction study

Study Record Dates

• First Submitted: September 4, 2022
• First Posted: September 8, 2022
• Study Start: September 12, 2022
• Primary Completion: January 28, 2023
• Study Completion: February 10, 2023
• Last Updated: March 23, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)