Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Ref · 1 trial · 1 indication
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Ref (TF2) | 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 | 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 | DRUG | Participants will receive single oral dose of MR-T2 on Day 1 in treatment period 1, 2, and 3 of Part A. |
| Evobrutinib MR-T3 | 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 | DRUG | Participants will receive single oral dose of MR-T4 on Day 1 in treatment period 1, 2, and 3 of Part A. |
| Evobrutinib MUPS-C1 | 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 | DRUG | Participants will receive single oral dose of MUPS-C2 on Day 1 in treatment period 1, 2, and 3 of Part B. |
| Evobrutinib MUPS-C3 | 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 | DRUG | 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 adapated | DRUG | Participants will receive single oral dose of MR-T adapted on Day 1 in treatment period 1, 2, and 3 of Part D. |
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 ...
Ref is an investigational small molecule being studied in healthy participants. It is currently in Phase 1 clinical development, with a completed trial evaluating its pharmacokinetics in healthy volunteers. Ref is not approved for any condition and remains under clinical investigation.
Ref is being developed by Merck KGaA, a biopharmaceutical company. The company is conducting clinical trials to evaluate the drug's pharmacokinetics in healthy participants. Merck KGaA's ticker symbol is MKGAF.
Ref is in Phase 1 clinical development. A Phase 1 trial has been completed, which studied the pharmacokinetics of different formulations of Ref in healthy participants. The drug is investigational and has not been approved for any use.
Ref has one completed Phase 1 trial, identified as NCT05245396. This study compared the pharmacokinetics of different formulations of Ref in healthy participants. The trial enrolled 58 participants and was conducted in the United Kingdom.
Ref is being studied in a clinical trial that compares different formulations of Evobrutinib. The trial title references Evobrutinib, indicating that Ref may be an alternative name or formulation of Evobrutinib. However, the exact relationship is not specified beyond this trial context.