Healthy VolunteersPhase 1NCT05532358
A Drug-Drug Interaction Study to Assess the CYP1A2 and CYP3A4 Interaction Potential of TEV-56286 (anle138b)
A Phase 1 study testing anle138b (TEV-56286) and Fluvoxamine 100 mg QD for 5 days in people with Healthy Volunteers, run by MODAG GmbH at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- anle138b (TEV-56286) and Fluvoxamine 100 mg QD for 5 days
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Sep 2022to 10 Feb 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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).
Read the 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.
- Conditions
- Healthy Volunteers
- Being tested
- anle138b (TEV-56286), Fluvoxamine 100 mg QD for 5 days
- Keywords
- anle138b (TEV-56286), alpha-Synuclein, Oligomer modulator, Multiple System Atrophy, Parkinson Disease, Alzheimer Disease, Neurodegenerative diseases, Tauopathies, Amyloid, Drug-drug interaction
- Medical subject headings
- Parkinson Disease 4, Autosomal Dominant Lewy Body, Multiple System Atrophy, Parkinson Disease, Alzheimer Disease, Neurodegenerative Diseases, Tauopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anle138b (TEV-56286)Drug
Also called Caffeine, Midazolam, Fluvoxamine
Anle138b (TEV-56286) as perpetrator
Fluvoxamine 100 mg QD for 5 daysDrug
Also called TEV-56286 150 mg QD for 14 days + 5 days of co-administation with fluvoxamine
Anle138b (TEV-56286) as victim
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Fluvoxamine 100 mg QD for 5 days |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
PK parameter: Cmax for caffeine.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: Day 19
Secondary outcomes (50)
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
PK parameter: Tmax
Measured: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
PK parameter: Tlag
Measured: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
PK parameter: lambda-z
Measured: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
PK parameter: T1/2
Measured: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
PK parameter: CL/F
Measured: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
PK parameter: Vz/F
Measured: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
PK parameter: Tmax
Measured: Day 19
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
PK parameter: lambda-z
Measured: Day 19
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
PK parameter: T1/2
Measured: Day 19
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
PK parameter: CL/F
Measured: Day 19
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
PK parameter: Vz/F
Measured: Day 19
Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
PK parameter: Tmax
Measured: Day 3
Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
PK parameter: Cmax
Measured: Day 3
Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
PK parameter: AUC (0-last)
Measured: Day 3
Oral pharmacokinetics (PK) of TEV-56286
PK parameter: Trough concentration for TEV-56286
Measured: Day 3-18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
PK parameter: Tmax
Measured: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
PK parameter: Cmax
Measured: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
PK parameter: Cmin
Measured: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
PK parameter: Cavg
Measured: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
PK parameter: AUC (0-tau)
Measured: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
PK parameter: AUC (0-last)
Measured: Day 18
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
PK parameter: Tmax
Measured: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
PK parameter: Cmax
Measured: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
PK parameter: Cmin
Measured: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
PK parameter: Cavg
Measured: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
PK parameter: AUC (0-tau)
Measured: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
PK parameter: AUC (0-last)
Measured: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
PK parameter: Trough concentration for fluvoxamine
Measured: Day 15-19
Oral pharmacokinetics (PK) of TEV-56286 after first dose administered as part of repeated administration
PK parameter: Tlag for TEV-56286
Measured: Day 1
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
PK parameter: Tmax
Measured: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
PK parameter: Cmax
Measured: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
PK parameter: AUC (0-tau)
Measured: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
PK parameter: lambda-z
Measured: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
PK parameter: T1/2
Measured: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
PK parameter: CL/F
Measured: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
PK parameter: Vz/F
Measured: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
PK parameter: AUC (0-last)
Measured: Day 14
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
PK parameter: Cmin
Measured: Day 14
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
PK parameter: Cavg
Measured: Day 14
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
PK parameter: Accumulation ratio
Measured: Day 14
Oral pharmacokinetics (PK) of metabolites paraxanthine and 1-hydroxy midazolam after single administration of caffeine and midazolam
PK parameter: Tmax
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 1 up to follow up visit (5-11 days post last TEV-56286 dose)
Number of participants reporting use of concomitant medications
Number of participants reporting use of concomitant medications
Measured: Day 1 up to follow up visit (5-11 days post last TEV-56286 dose)
Columbia-Suicide Severity Rating Scale (C-SSRS) total score
Columbia-Suicide Severity Rating Scale (C-SSRS) total score
Measured: Day 3 to day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2022
- Study start12 Sep 2022
- Primary completion28 Jan 2023
- Study completion10 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Drug drug interaction study
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- MODAG GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Aptuit, Quotient Sciences, Teva Pharmaceutical Industries, Ltd.
- Responsible party
- Sponsor
- Investigators
- Nand Singh, MD, Principal investigator, Quotient Sciences Mere Way Ruddington Fields Ruddington Nottingham NG11 6JS, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05532358
- Sponsor's protocol ID
- anle138b-P1-03
- Other IDs
- 2022-002467-30
- Status last verified
- Mar 2023
- First submitted
- 4 Sep 2022
- Last updated
- 23 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35500536Wagner 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.
PubMed 23604588Drug 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.
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).
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05532358
- Acronym / sponsor ID
- anle138b-P1-03
- Conditions
- Healthy Volunteers
- Keywords
- anle138b (TEV-56286), alpha-Synuclein, Oligomer modulator, Multiple System Atrophy, Parkinson Disease, Alzheimer Disease, Neurodegenerative diseases, Tauopathies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- MODAG GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Aptuit, Quotient Sciences, Teva Pharmaceutical Industries, Ltd.
- Study start
- 12 Sep 2022 (actual)
- Primary completion
- 28 Jan 2023 (actual)
- Study completion
- 10 Feb 2023 (actual)
- First posted
- 8 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Drug drug interaction study
| Arm | Type | Receives |
|---|---|---|
| anle138b (TEV-56286) as perpetrator (part I) | Experimental | Drug: anle138b (TEV-56286)Drug: TEV-56286 300 mg QD (single dose and multiple dose for 14 days) Victim drugs: Caffeine 200 mg Midazolam 2 mg |
| anle138b (TEV-56286) as victim (part II) | Experimental | Drug: Fluvoxamine 100 mg QD for 5 daysDrug: fluvoxamine 100 mg QD for 5 days Victim drug: TEV-56286 150 mg QD for 14 days + 5 days of co-administation with fluvoxamine |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anle138b (TEV-56286)Also: Caffeine, Midazolam, FluvoxamineAnle138b (TEV-56286) as perpetrator | Drug | anle138b (TEV-56286) as perpetrator (part I) |
| Fluvoxamine 100 mg QD for 5 daysAlso: TEV-56286 150 mg QD for 14 days + 5 days of co-administation with fluvoxamineAnle138b (TEV-56286) as victim | Drug | anle138b (TEV-56286) as victim (part II) |
Primary outcome
Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 1
PK parameter: Cmax for caffeine.
Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 1
PK parameter: AUC(0-inf) for caffeine.
Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 1
PK parameter: AUC (0-last) for caffeine.
Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 1
PK parameter: Cmax for midazolam.
Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 1
PK parameter: AUC(0-inf) for midazolam.
Oral pharmacokinetics (PK) of midazolam administered without TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 1
PK parameter: AUC (0-last) for midazolam.
Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 3
Cmax for caffeine.
Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 3
PK parameter: AUC(0-inf) for caffeine.
Oral pharmacokinetics (PK) of caffeine after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 3
PK parameter: AUC (0-last) for caffeine.
Oral pharmacokinetics (PK) of midazolam after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 3
Cmax for midazolam
Oral pharmacokinetics (PK) of midazolam after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 3
PK parameter: AUC(0-inf) for midazolam.
Oral pharmacokinetics (PK) of midazolam after single co-administration with TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 3
PK parameter: AUC (0-last) for midazolam.
Oral pharmacokinetics (PK) of caffeine after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 18
PK parameter: Cmax for caffeine.
Oral pharmacokinetics (PK) of caffeine after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 18
AUC(0-inf) for caffeine.
Oral pharmacokinetics (PK) of caffeine after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 18
PK parameter: AUC (0-last) for caffeine.
Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 18
PK parameter: Cmax for midazolam.
Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 18
PK parameter: AUC(0-inf) for midazolam.
Oral pharmacokinetics (PK) of midazolam after repeated administration of TEV-56286 in healthy volunteers in the fasted state (Part I).
Time frame: Day 18
PK parameter: AUC (0-last) for midazolam.
Oral pharmacokinetics (PK) of TEV-56286 without fluvoxamine in healthy volunteers after repeated administration in the fasted state (Part II).
Time frame: Day 14
PK parameter: Cmax for TEV-56286.
Oral pharmacokinetics (PK) of TEV-56286 without fluvoxamine in healthy volunteers after repeated administration in the fasted state (Part II).
Time frame: Day 14
PK parameter: AUC(0-tau) for TEV-56286.
Oral pharmacokinetics (PK) of TEV-56286 in healthy volunteers after repeated co-administration with fluvoxamine in the fasted state.
Time frame: Day 19
PK parameter: Cmax for TEV-56286 (Part II).
Oral pharmacokinetics (PK) of TEV-56286 in healthy volunteers after repeated co-administration with fluvoxamine in the fasted state.
Time frame: Day 19
PK parameter: AUC(0-tau) for TEV-56286 (Part II).
50 secondary outcomes
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
Time frame: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
Time frame: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
Time frame: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
Time frame: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
Time frame: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of substrates caffeine and midazolam
Time frame: Day 1, Day 3, Day 18
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
Time frame: Day 19
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
Time frame: Day 19
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
Time frame: Day 19
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
Time frame: Day 19
Oral pharmacokinetics (PK) of TEV-56286 after repeated co-administration with fluvoxamine
Time frame: Day 19
Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
Time frame: Day 3
Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
Time frame: Day 3
Oral pharmacokinetics (PK) of TEV-56286 as perpetrator drug after co-administration with caffeine and midazolam
Time frame: Day 3
Oral pharmacokinetics (PK) of TEV-56286
Time frame: Day 3-18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
Time frame: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
Time frame: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
Time frame: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
Time frame: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
Time frame: Day 18
Oral pharmacokinetics (PK) of TEV-56286 after single co-administration with caffeine and midazolam
Time frame: Day 18
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
Time frame: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
Time frame: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
Time frame: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
Time frame: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
Time frame: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
Time frame: Day 19
Oral pharmacokinetics (PK) of fluvoxamine after repeated co-administration with TEV-56286
Time frame: Day 15-19
Oral pharmacokinetics (PK) of TEV-56286 after first dose administered as part of repeated administration
Time frame: Day 1
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
Time frame: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
Time frame: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
Time frame: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
Time frame: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
Time frame: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
Time frame: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following single dose and multiple dose
Time frame: Day 1, Day 14
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
Time frame: Day 14
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
Time frame: Day 14
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
Time frame: Day 14
Oral pharmacokinetics (PK) of TEV-56286 following multiple dose
Time frame: Day 14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2023.
- Background: PubMed 35500536Levin 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.
- Background: PubMed 23604588Wagner 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.
- BackgroundDrug 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.
- BackgroundClinical 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).
- Description Sponsor HomepageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nand Singh, MD principal investigator
Quotient Sciences Mere Way Ruddington Fields Ruddington Nottingham NG11 6JS, UK
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing anle138b (TEV-56286) and Fluvoxamine 100 mg QD for 5 days in people with Healthy Volunteers, run by MODAG GmbH at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oral pharmacokinetics (PK) of caffeine administered without TEV-56286 in healthy volunteers in the fasted state (Part I). (time frame: Day 1). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05532358, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2023.