Study Comparing Pharmacokinetics of Different Formulations of Evobrutinib in Healthy Participants

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Evobrutinib MUPS-C3; Drug: Evobrutinib MR-T1; Drug: Evobrutinib MUPS-C2; Drug: Evobrutinib MR-T adapated; Drug: Evobrutinib MR-T4; Drug: Evobrutinib MUPS-C4; Drug: Evobrutinib MR-T3; Drug: Evobrutinib MR-T2; Drug: Ref (TF2); Drug: Evobrutinib MUPS-C1

Study type: Interventional

Funder types: Industry

Identifiers

NCT05245396

MS200527_0091

2021-005056-11 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 58 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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58 participants in 14 patient groups

Part A: Evobrutinib: Treatment Sequence 1

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MR-T2

Drug: Evobrutinib MR-T1

Part A: Evobrutinib: Treatment Sequence 2

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MR-T2

Drug: Evobrutinib MR-T1

Part A: Evobrutinib: Treatment Sequence 3

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MR-T2

Drug: Evobrutinib MR-T1

Part A: Evobrutinib: Treatment Sequence 4

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MR-T3

Drug: Evobrutinib MR-T4

Part A: Evobrutinib: Treatment Sequence 5

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MR-T3

Drug: Evobrutinib MR-T4

Part A: Evobrutinib: Treatment Sequence 6

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MR-T3

Drug: Evobrutinib MR-T4

Part B: Evobrutinib: Treatment Sequence 1

Experimental group

Description:

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.

Treatment:

Drug: Evobrutinib MUPS-C1

Drug: Ref (TF2)

Drug: Evobrutinib MUPS-C2

Part B: Evobrutinib: Treatment Sequence 2

Experimental group

Description:

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.

Treatment:

Drug: Evobrutinib MUPS-C1

Drug: Ref (TF2)

Drug: Evobrutinib MUPS-C2

Part B: Evobrutinib: Treatment Sequence 3

Experimental group

Description:

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.

Treatment:

Drug: Evobrutinib MUPS-C1

Drug: Ref (TF2)

Drug: Evobrutinib MUPS-C2

Part C: Evobrutinib: Treatment Sequence 4

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MUPS-C4

Drug: Evobrutinib MUPS-C3

Part C: Evobrutinib: Treatment Sequence 5

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MUPS-C4

Drug: Evobrutinib MUPS-C3

Part C: Evobrutinib: Treatment Sequence 6

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MUPS-C4

Drug: Evobrutinib MUPS-C3

Part D: Evobrutinib: Treatment Sequence 1

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MR-T adapated

Drug: Evobrutinib MR-T1

Part D: Evobrutinib: Treatment Sequence 2

Experimental group

Description:

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.

Treatment:

Drug: Ref (TF2)

Drug: Evobrutinib MR-T adapated

Drug: Evobrutinib MR-T1