HealthyPhase 1NCT05245396

Study Comparing Pharmacokinetics of Different Formulations of Evobrutinib in Healthy Participants

A Phase 1 study testing Ref (TF2), Evobrutinib MR-T1 and Evobrutinib MR-T2 in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety and tolerability of evobrutinib after oral administration of immediate release (IR) and modified release (MR) formulations in healthy participants. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Ref (TF2), Evobrutinib MR-T1 and Evobrutinib MR-T2
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 58 participants
Where: 1 siteUnited Kingdom
Study dates: 2 Feb 2022to 14 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

Participants are overtly healthy as determined by medical evaluation, including comprehensive clinical assessment (detailed medical history and a complete physical examination), ECG, and laboratory investigations (hematology and biochemistry)
Participants have a body weight within 50.0 to 100.0 kilogram (kg) and body mass index (BMI) within the range 19 to 32 kilogram per meter square (kg/m^2) (inclusive)
Other protocol defined inclusion criteria could apply

Who cannot join

Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, metabolic, hematological, lymphatic, neurological (including epilepsy), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
Participants with history of any malignancy
Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines (e.g. SARS-CoV-2 vaccines) is allowed until 2 weeks before the admission to the CRU
Medical history and physical examination results that include any ongoing clinically relevant findings as judged by the Investigator
Moderate or strong inhibitors or inducers of CYP3A4/5 or Pgp within 4 weeks prior to the first administration of study intervention
Other protocol-defined exclusion criteria could apply

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Quotient Clinical Ltd
Nottingham, NG11

Other trials in United Kingdom

About this study

Official title: A Phase I, Single-site, Open-label, Partially Randomized Study to Evaluate the Relative Bioavailability and Pharmacokinetics of Evobrutinib Following Administration of Different Formulations in Healthy Participants

Conditions: Healthy
Being tested: Ref (TF2), Evobrutinib MR-T1, Evobrutinib MR-T2, Evobrutinib MR-T3, Evobrutinib MR-T4
Keywords: Bruton's tyrosine kinase, delayed release, multiparticulate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ref (TF2)Drug
Also called M2951
Participants will receive 2 single oral doses of Ref (TF2) on Day 1 in treatment period 1, 2, or 3 of Part A, B, C and D.
Evobrutinib MR-T1Drug
Also called M2951
Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.
Evobrutinib MR-T2Drug
Also called M2951
Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.
Evobrutinib MR-T3Drug
Also called M2951
Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.
Evobrutinib MR-T4Drug
Also called M2951
Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.
Evobrutinib MUPS-C1Drug
Also called M2951
Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.
Evobrutinib MUPS-C2Drug
Also called M2951
Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.
Evobrutinib MUPS-C3Drug
Also called M2951
Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.
Evobrutinib MUPS-C4Drug
Also called M2951
Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.
Evobrutinib MR-T adapatedDrug
Also called M2951
Participants will receive single oral dose of MR-T adapted on Day 1 in treatment period 1, 2, and 3 of Part D.

Study groups in NCT05245396
Study group	Role	What they receive
Part A: Evobrutinib: Treatment Sequence 1	Experimental	Participants will receive single oral dose of modified release evobrutinib tablet-1 (MR-T1) on Day 1 in treatment period 1, followed by single oral dose of modified release tablet-2 (MR-T2) on Day 1 in treatment period 2, followed by two single oral doses of immediate release (IR) oral tablet [Ref (TF2)] on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or multiparticulate system capsules (MUPS-C) formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MR-T1; Drug: Evobrutinib MR-T2
Part A: Evobrutinib: Treatment Sequence 2	Experimental	Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by single oral dose of MR-T1 on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MR-T1; Drug: Evobrutinib MR-T2
Part A: Evobrutinib: Treatment Sequence 3	Experimental	Participants will receive two single oral doses of Ref (TF2) on Day 1 in treatment period 1, followed by single oral dose of MR-T1 on Day 1 in treatment period 2, followed by single oral dose of MR-T2 on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MR-T1; Drug: Evobrutinib MR-T2
Part A: Evobrutinib: Treatment Sequence 4	Experimental	Participants will receive single oral dose of modified release evobrutinib tablet-3 (MR-T3) on Day 1 in treatment period 1, followed by single oral dose of modified release tablet-4 (MR-T4) on Day 1 in treatment period 2, followed by two single oral doses of immediate release (IR) oral tablet [Ref (TF2)] on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or multiparticulate system capsules (MUPS-C) formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MR-T3; Drug: Evobrutinib MR-T4
Part A: Evobrutinib: Treatment Sequence 5	Experimental	Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by single oral dose of MR-T3 on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MR-T3; Drug: Evobrutinib MR-T4
Part A: Evobrutinib: Treatment Sequence 6	Experimental	Participants will receive two single oral doses of Ref (TF2) on Day 1 in treatment period 1, followed by single oral dose of MR-T3 on Day 1 in treatment period 2, followed by single oral dose of MR-T4 on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MR-T3; Drug: Evobrutinib MR-T4
Part B: Evobrutinib: Treatment Sequence 1	Experimental	Participants will receive single oral dose of MUPS-C1 evobrutinib on Day 1 in treatment period 1, followed by single oral dose of MUPS-C2 on Day 1 in treatment period 2, followed by two single oral doses of Ref (TF2) on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MUPS-C1; Drug: Evobrutinib MUPS-C2
Part B: Evobrutinib: Treatment Sequence 2	Experimental	Participants will receive single oral dose of MUPS-C2 evobrutinib on Day 1 in treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by single oral dose of MUPS-C2 on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MUPS-C1; Drug: Evobrutinib MUPS-C2
Part B: Evobrutinib: Treatment Sequence 3	Experimental	Participants will receive two single oral doses of Ref (TF2) evobrutinib on Day 1 in treatment period 1, followed by single oral dose of MUPS-C1 on Day 1 in treatment period 2, followed by single oral dose of MUPS-C2 on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MUPS-C1; Drug: Evobrutinib MUPS-C2
Part C: Evobrutinib: Treatment Sequence 4	Experimental	Participants will receive single oral dose of MUPS-C3 evobrutinib on Day 1 in treatment period 1, followed by single oral dose of MUPS-C4 on Day 1 in treatment period 2, followed by two single oral doses of Ref (TF2) on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MUPS-C3; Drug: Evobrutinib MUPS-C4
Part C: Evobrutinib: Treatment Sequence 5	Experimental	Participants will receive single oral dose of MUPS-C4 evobrutinib on Day 1 in treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by single oral dose of MUPS-C3 on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MUPS-C3; Drug: Evobrutinib MUPS-C4
Part C: Evobrutinib: Treatment Sequence 6	Experimental	Participants will receive two single oral doses of Ref (TF2) evobrutinib on Day 1 in treatment period 1, followed by single oral dose of MUPS-C3 on Day 1 in treatment period 2, followed by single oral dose of MUPS-C4 on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5. Receives: Drug: Ref (TF2); Drug: Evobrutinib MUPS-C3; Drug: Evobrutinib MUPS-C4
Part D: Evobrutinib: Treatment Sequence 1	Experimental	Participants will receive single oral dose of MR-T adapted on Day 1 of treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by 1 sequential period 3. There will be 72 hours washout period between Periods 1 and 2 and 28 days between Period 2 and 3. Receives: Drug: Ref (TF2); Drug: Evobrutinib MR-T1; Drug: Evobrutinib MR-T adapated
Part D: Evobrutinib: Treatment Sequence 2	Experimental	Participants will receive two single oral doses of Ref (TF2) on Day 1 of treatment period 1, followed by single oral dose of MR-T adapted on Day 1 in treatment period 2, followed by 1 sequential period 3. There will be 72 hours washout period between Periods 1 and 2 and 28 days between Period 2 and 3. Receives: Drug: Ref (TF2); Drug: Evobrutinib MR-T1; Drug: Evobrutinib MR-T adapated

What is being measured

The primary outcome is the main question the study is designed to answer.

Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose [Frel(AUC0-24)] of Evobrutinib Modified-Release Formulation Compared to Immediate-Release Evobrutinib Reference Formulation
Measured: Pre-dose up to 72 hours post-dose on Day 4
Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to Infinity [Frel(AUC0-inf)] of Evobrutinib Modified-Release Formulation Compared to Immediate-Release Evobrutinib Reference Formulation
Measured: Pre-dose up to 72 hours post-dose on Day 4

Secondary outcomes (2)

Number of Participants with Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Abnormal Laboratory Test Results, Abnormal Vital Signs and Abnormal Electrocardiogram (ECG) Measurements
Measured: Up to Day 123
Pharmacokinetic Plasma Concentration of Evobrutinib Formulations
Measured: Pre-dose up to 72 hours post-dose on Day 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Feb 202214 Feb 2023

First posted18 Feb 2022
Study start2 Feb 2022
Primary completion14 Feb 2023
Study completion14 Feb 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HealthyStudies 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: Randomised
Intervention model: Sequential
Model description: Part A, B and C, periods 1 to 3 will be an incomplete cross-over; Part A, B and C, periods 4 and 5 are sequential. Part D, periods 1 and 2 will be 2-sequence cross-over design with 2 treatment sequences; Part D, period 3 is optional.
Masking: None (open label)
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05245396
Sponsor's protocol ID: MS200527_0091
Other IDs: 2021-005056-11
Status last verified: Mar 2023
First submitted: 24 Jan 2022
Last updated: 22 Mar 2023
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website http://bit.ly/IPD21

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Single-site, Open-label, Partially Randomized Study to Evaluate the Relative Bioavailability and Pharmacokinetics of Evobrutinib Following Administration of Different Formulations in Healthy Participants
ClinicalTrials.gov ID: NCT05245396
Acronym / sponsor ID: MS200527_0091
Conditions: Healthy
Keywords: Bruton's tyrosine kinase, delayed release, multiparticulate
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Collaborators: Merck KGaA, Darmstadt, Germany
Study start: 2 Feb 2022 (actual)
Primary completion: 14 Feb 2023 (actual)
Study completion: 14 Feb 2023 (actual)
First posted: 18 Feb 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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 14
Model description: Part A, B and C, periods 1 to 3 will be an incomplete cross-over; Part A, B and C, periods 4 and 5 are sequential. Part D, periods 1 and 2 will be 2-sequence cross-over design with 2 treatment sequences; Part D, period 3 is optional.

Arm	Type	Receives
Part A: Evobrutinib: Treatment Sequence 1	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MR-T1, Drug: Evobrutinib MR-T2Participants will receive single oral dose of modified release evobrutinib tablet-1 (MR-T1) on Day 1 in treatment period 1, followed by single oral dose of modified release tablet-2 (MR-T2) on Day 1 in treatment period 2, followed by two single oral doses of immediate release (IR) oral tablet [Ref (TF2)] on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or multiparticulate system capsules (MUPS-C) formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part A: Evobrutinib: Treatment Sequence 2	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MR-T1, Drug: Evobrutinib MR-T2Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by single oral dose of MR-T1 on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part A: Evobrutinib: Treatment Sequence 3	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MR-T1, Drug: Evobrutinib MR-T2Participants will receive two single oral doses of Ref (TF2) on Day 1 in treatment period 1, followed by single oral dose of MR-T1 on Day 1 in treatment period 2, followed by single oral dose of MR-T2 on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part A: Evobrutinib: Treatment Sequence 4	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MR-T3, Drug: Evobrutinib MR-T4Participants will receive single oral dose of modified release evobrutinib tablet-3 (MR-T3) on Day 1 in treatment period 1, followed by single oral dose of modified release tablet-4 (MR-T4) on Day 1 in treatment period 2, followed by two single oral doses of immediate release (IR) oral tablet [Ref (TF2)] on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or multiparticulate system capsules (MUPS-C) formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part A: Evobrutinib: Treatment Sequence 5	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MR-T3, Drug: Evobrutinib MR-T4Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by single oral dose of MR-T3 on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part A: Evobrutinib: Treatment Sequence 6	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MR-T3, Drug: Evobrutinib MR-T4Participants will receive two single oral doses of Ref (TF2) on Day 1 in treatment period 1, followed by single oral dose of MR-T3 on Day 1 in treatment period 2, followed by single oral dose of MR-T4 on Day 1 in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part B: Evobrutinib: Treatment Sequence 1	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MUPS-C1, Drug: Evobrutinib MUPS-C2Participants will receive single oral dose of MUPS-C1 evobrutinib on Day 1 in treatment period 1, followed by single oral dose of MUPS-C2 on Day 1 in treatment period 2, followed by two single oral doses of Ref (TF2) on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part B: Evobrutinib: Treatment Sequence 2	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MUPS-C1, Drug: Evobrutinib MUPS-C2Participants will receive single oral dose of MUPS-C2 evobrutinib on Day 1 in treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by single oral dose of MUPS-C2 on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part B: Evobrutinib: Treatment Sequence 3	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MUPS-C1, Drug: Evobrutinib MUPS-C2Participants will receive two single oral doses of Ref (TF2) evobrutinib on Day 1 in treatment period 1, followed by single oral dose of MUPS-C1 on Day 1 in treatment period 2, followed by single oral dose of MUPS-C2 on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part C: Evobrutinib: Treatment Sequence 4	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MUPS-C3, Drug: Evobrutinib MUPS-C4Participants will receive single oral dose of MUPS-C3 evobrutinib on Day 1 in treatment period 1, followed by single oral dose of MUPS-C4 on Day 1 in treatment period 2, followed by two single oral doses of Ref (TF2) on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part C: Evobrutinib: Treatment Sequence 5	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MUPS-C3, Drug: Evobrutinib MUPS-C4Participants will receive single oral dose of MUPS-C4 evobrutinib on Day 1 in treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by single oral dose of MUPS-C3 on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part C: Evobrutinib: Treatment Sequence 6	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MUPS-C3, Drug: Evobrutinib MUPS-C4Participants will receive two single oral doses of Ref (TF2) evobrutinib on Day 1 in treatment period 1, followed by single oral dose of MUPS-C3 on Day 1 in treatment period 2, followed by single oral dose of MUPS-C4 on Day 1 of in treatment period 3, followed by 2 sequential periods 4 and 5. The best MR-T and /or MUPS-C formulation from period 1, 2, and 3 will be tested with additional optimization to choose the best overall formulation in treatment period 4. The best overall formulation from Period 4 may be further tested in treatment period 5 under fed or fasted conditions. There will be 72 hours washout period between Periods 1 to 3 and 28 days between Period 3 and 4 and Period 4 and 5.
Part D: Evobrutinib: Treatment Sequence 1	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MR-T1, Drug: Evobrutinib MR-T adapatedParticipants will receive single oral dose of MR-T adapted on Day 1 of treatment period 1, followed by two single oral doses of Ref (TF2) on Day 1 in treatment period 2, followed by 1 sequential period 3. There will be 72 hours washout period between Periods 1 and 2 and 28 days between Period 2 and 3.
Part D: Evobrutinib: Treatment Sequence 2	Experimental	Drug: Ref (TF2), Drug: Evobrutinib MR-T1, Drug: Evobrutinib MR-T adapatedParticipants will receive two single oral doses of Ref (TF2) on Day 1 of treatment period 1, followed by single oral dose of MR-T adapted on Day 1 in treatment period 2, followed by 1 sequential period 3. There will be 72 hours washout period between Periods 1 and 2 and 28 days between Period 2 and 3.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Participants are overtly healthy as determined by medical evaluation, including comprehensive clinical assessment (detailed medical history and a complete physical examination), ECG, and laboratory investigations (hematology and biochemistry)
Participants have a body weight within 50.0 to 100.0 kilogram (kg) and body mass index (BMI) within the range 19 to 32 kilogram per meter square (kg/m^2) (inclusive)
Other protocol defined inclusion criteria could apply

Key exclusion criteria (6 listed)

Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, metabolic, hematological, lymphatic, neurological (including epilepsy), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
Participants with history of any malignancy
Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines (e.g. SARS-CoV-2 vaccines) is allowed until 2 weeks before the admission to the CRU
Medical history and physical examination results that include any ongoing clinically relevant findings as judged by the Investigator
Moderate or strong inhibitors or inducers of CYP3A4/5 or Pgp within 4 weeks prior to the first administration of study intervention

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
Ref (TF2)Also: M2951Participants will receive 2 single oral doses of Ref (TF2) on Day 1 in treatment period 1, 2, or 3 of Part A, B, C and D.	Drug	Part A: Evobrutinib: Treatment Sequence 1, Part A: Evobrutinib: Treatment Sequence 2, Part A: Evobrutinib: Treatment Sequence 3, Part A: Evobrutinib: Treatment Sequence 4, Part A: Evobrutinib: Treatment Sequence 5, Part A: Evobrutinib: Treatment Sequence 6, Part B: Evobrutinib: Treatment Sequence 1, Part B: Evobrutinib: Treatment Sequence 2, Part B: Evobrutinib: Treatment Sequence 3, Part C: Evobrutinib: Treatment Sequence 4, Part C: Evobrutinib: Treatment Sequence 5, Part C: Evobrutinib: Treatment Sequence 6, Part D: Evobrutinib: Treatment Sequence 1, Part D: Evobrutinib: Treatment Sequence 2
Evobrutinib MR-T1Also: M2951Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.	Drug	Part A: Evobrutinib: Treatment Sequence 1, Part A: Evobrutinib: Treatment Sequence 2, Part A: Evobrutinib: Treatment Sequence 3, Part D: Evobrutinib: Treatment Sequence 1, Part D: Evobrutinib: Treatment Sequence 2
Evobrutinib MR-T2Also: M2951Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.	Drug	Part A: Evobrutinib: Treatment Sequence 1, Part A: Evobrutinib: Treatment Sequence 2, Part A: Evobrutinib: Treatment Sequence 3
Evobrutinib MR-T3Also: M2951Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.	Drug	Part A: Evobrutinib: Treatment Sequence 4, Part A: Evobrutinib: Treatment Sequence 5, Part A: Evobrutinib: Treatment Sequence 6
Evobrutinib MR-T4Also: M2951Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.	Drug	Part A: Evobrutinib: Treatment Sequence 4, Part A: Evobrutinib: Treatment Sequence 5, Part A: Evobrutinib: Treatment Sequence 6
Evobrutinib MUPS-C1Also: M2951Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.	Drug	Part B: Evobrutinib: Treatment Sequence 1, Part B: Evobrutinib: Treatment Sequence 2, Part B: Evobrutinib: Treatment Sequence 3
Evobrutinib MUPS-C2Also: M2951Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.	Drug	Part B: Evobrutinib: Treatment Sequence 1, Part B: Evobrutinib: Treatment Sequence 2, Part B: Evobrutinib: Treatment Sequence 3
Evobrutinib MUPS-C3Also: M2951Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.	Drug	Part C: Evobrutinib: Treatment Sequence 4, Part C: Evobrutinib: Treatment Sequence 5, Part C: Evobrutinib: Treatment Sequence 6
Evobrutinib MUPS-C4Also: M2951Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.	Drug	Part C: Evobrutinib: Treatment Sequence 4, Part C: Evobrutinib: Treatment Sequence 5, Part C: Evobrutinib: Treatment Sequence 6
Evobrutinib MR-T adapatedAlso: M2951Participants will receive single oral dose of MR-T adapted on Day 1 in treatment period 1, 2, and 3 of Part D.	Drug	Part D: Evobrutinib: Treatment Sequence 1, Part D: Evobrutinib: Treatment Sequence 2

Primary outcome

Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose [Frel(AUC0-24)] of Evobrutinib Modified-Release Formulation Compared to Immediate-Release Evobrutinib Reference Formulation
Time frame: Pre-dose up to 72 hours post-dose on Day 4
Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to Infinity [Frel(AUC0-inf)] of Evobrutinib Modified-Release Formulation Compared to Immediate-Release Evobrutinib Reference Formulation
Time frame: Pre-dose up to 72 hours post-dose on Day 4

2 secondary outcomes

Number of Participants with Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Abnormal Laboratory Test Results, Abnormal Vital Signs and Abnormal Electrocardiogram (ECG) Measurements
Time frame: Up to Day 123
Pharmacokinetic Plasma Concentration of Evobrutinib Formulations
Time frame: Pre-dose up to 72 hours post-dose on Day 4

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 22 Mar 2023.
Trial Awareness and Transparency websiteLink provided by the sponsor.
Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
Individual participant dataSharing planned: No. We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website http://bit.ly/IPD21

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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.

Medical Responsible study director

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 6 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 22 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?

Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose [Frel(AUC0-24)] of Evobrutinib Modified-Release Formulation Compared to Immediate-Release Evobrutinib Reference Formulation (time frame: Pre-dose up to 72 hours post-dose on Day 4). The study lists 2 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 NCT05245396.

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 22 Mar 2023.