Study Comparing Pharmacokinetics of Different Formulations of Evobrutinib in Healthy Participants

March 20, 2023 updated by: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Nottingham, United Kingdom, NG11
        • Quotient Clinical Ltd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Evobrutinib: Treatment Sequence 1
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.
Drug: Evobrutinib MR-T1
Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Evobrutinib MR-T2
Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part A: Evobrutinib: Treatment Sequence 2
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.
Drug: Evobrutinib MR-T1
Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Evobrutinib MR-T2
Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part A: Evobrutinib: Treatment Sequence 3
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.
Drug: Evobrutinib MR-T1
Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Evobrutinib MR-T2
Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part A: Evobrutinib: Treatment Sequence 4
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.
Drug: Evobrutinib MR-T3
Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Evobrutinib MR-T4
Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part A: Evobrutinib: Treatment Sequence 5
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.
Drug: Evobrutinib MR-T3
Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Evobrutinib MR-T4
Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part A: Evobrutinib: Treatment Sequence 6
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.
Drug: Evobrutinib MR-T3
Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Evobrutinib MR-T4
Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part B: Evobrutinib: Treatment Sequence 1
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.
Drug: Evobrutinib MUPS-C1
Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C2
Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part B: Evobrutinib: Treatment Sequence 2
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.
Drug: Evobrutinib MUPS-C1
Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C2
Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part B: Evobrutinib: Treatment Sequence 3
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.
Drug: Evobrutinib MUPS-C1
Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C2
Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Experimental: Part C: Evobrutinib: Treatment Sequence 4
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.
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C3
Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C4
Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.
Other Names:
  • M2951
Experimental: Part C: Evobrutinib: Treatment Sequence 5
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.
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C3
Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C4
Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.
Other Names:
  • M2951
Experimental: Part C: Evobrutinib: Treatment Sequence 6
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.
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C3
Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.
Other Names:
  • M2951
Drug: Evobrutinib MUPS-C4
Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.
Other Names:
  • M2951
Experimental: Part D: Evobrutinib: Treatment Sequence 1
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.
Drug: Evobrutinib MR-T1
Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Drug: Evobrutinib MR-T adapated
Participants will receive single oral dose of MR-T adapted on Day 1 in treatment period 1, 2, and 3 of Part D.
Other Names:
  • M2951
Experimental: Part D: Evobrutinib: Treatment Sequence 2
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.
Drug: Evobrutinib MR-T1
Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.
Other Names:
  • M2951
Drug: Ref (TF2)
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.
Other Names:
  • M2951
Drug: Evobrutinib MR-T adapated
Participants will receive single oral dose of MR-T adapted on Day 1 in treatment period 1, 2, and 3 of Part D.
Other Names:
  • M2951

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
Pre-dose up to 72 hours post-dose on Day 4

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Up to Day 123
Pharmacokinetic Plasma Concentration of Evobrutinib Formulations
Time Frame: Pre-dose up to 72 hours post-dose on Day 4
Pre-dose up to 72 hours post-dose on Day 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2022

Primary Completion (Actual)

February 14, 2023

Study Completion (Actual)

February 14, 2023

Study Registration Dates

First Submitted

January 24, 2022

First Submitted That Met QC Criteria

February 8, 2022

First Posted (Actual)

February 18, 2022

Study Record Updates

Last Update Posted (Actual)

March 22, 2023

Last Update Submitted That Met QC Criteria

March 20, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • MS200527_0091
  • 2021-005056-11 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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