Study Comparing Pharmacokinetics of Different Formulations of Evobrutinib in Healthy Participants

NCT ID: NCT05245396

Last Updated: 2023-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-02

Study Completion Date

2023-02-14

Brief Summary

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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.

Detailed Description

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Conditions

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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-T1

Intervention Type DRUG

Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.

Evobrutinib MR-T2

Intervention Type DRUG

Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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-T1

Intervention Type DRUG

Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.

Evobrutinib MR-T2

Intervention Type DRUG

Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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-T1

Intervention Type DRUG

Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.

Evobrutinib MR-T2

Intervention Type DRUG

Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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-T3

Intervention Type DRUG

Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.

Evobrutinib MR-T4

Intervention Type DRUG

Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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-T3

Intervention Type DRUG

Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.

Evobrutinib MR-T4

Intervention Type DRUG

Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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-T3

Intervention Type DRUG

Participants will receive single oral dose of MR-T3 on Day 1 in treatment period 1, 2, and 3 of Part A.

Evobrutinib MR-T4

Intervention Type DRUG

Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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 MUPS-C1

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.

Evobrutinib MUPS-C2

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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 MUPS-C1

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.

Evobrutinib MUPS-C2

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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 MUPS-C1

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C1 on Day 1 in treatment period 1, 2, and 3 of Part B.

Evobrutinib MUPS-C2

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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 MUPS-C3

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.

Evobrutinib MUPS-C4

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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 MUPS-C3

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.

Evobrutinib MUPS-C4

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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 MUPS-C3

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C3 on Day 1 in treatment period 1, 2, and 3 of Part C.

Evobrutinib MUPS-C4

Intervention Type DRUG

Participants will receive single oral dose of MUPS-C4 on Day 1 in treatment period 1, 2, and 3 of Part C.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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-T1

Intervention Type DRUG

Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.

Evobrutinib MR-T adapated

Intervention Type DRUG

Participants will receive single oral dose of MR-T adapted on Day 1 in treatment period 1, 2, and 3 of Part D.

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.

Group Type EXPERIMENTAL

Ref (TF2)

Intervention Type DRUG

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-T1

Intervention Type DRUG

Participants will receive single oral dose of MR-T1 on Day 1 in treatment period 1, 2, and 3 of Part A.

Evobrutinib MR-T adapated

Intervention Type DRUG

Participants will receive single oral dose of MR-T adapted on Day 1 in treatment period 1, 2, and 3 of Part D.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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M2951 M2951 M2951 M2951 M2951 M2951 M2951 M2951 M2951 M2951

Eligibility Criteria

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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)

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

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

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

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

Locations

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Quotient Clinical Ltd

Nottingham, , United Kingdom

Site Status

Countries

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United Kingdom

Related Links

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Other Identifiers

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2021-005056-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200527_0091

Identifier Type: -

Identifier Source: org_study_id

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