Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Evobrutinib · 5 trials · 2 indications
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Cmax was obtained from plasma concentration time curve.
| Arm | Type | Description |
|---|---|---|
| Evobrutinib plus Carbamazepine | EXPERIMENTAL | Participants received a single oral dose of Evobrutinib 45 mg on Day 1 and Day 19 under fed condition followed by Cabamazepine 100 mg on Days 2 and 3, 200 mg on Days 4 and 5 and then 300 mg from Days 6 to 19 and were titrated back to 200 mg from Days 20 to 22 and 100 mg on Days 23 to 25 twice daily. |
| Evobrutinib: Treatment Sequence 1: A-B-C | EXPERIMENTAL | Participants will receive single oral dose of TF1 (Treatment A) evobrutinib on Day 1 under fasted condition in period 1, followed by single oral dose of TF2 (Treatment B) on Day 3 under fasted condition in period 2, followed by TF2 (Treatment C) on Day 5 under fed condition in period 3. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence 2: A-C-B | EXPERIMENTAL | Participants will receive single oral dose of TF1 (Treatment A) evobrutinib on Day 1 under fasted condition in period 1, followed by TF2 (Treatment C) on Day 3 under fed condition in period 2, followed by single oral dose of TF2 (Treatment B) on Day 5 under fasted condition in period 3. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence 3: B-A-C | EXPERIMENTAL | Participants will receive single oral dose of TF2 (Treatment B) on Day 1 under fasted condition in period 1, followed by single oral dose of TF1 (Treatment A) evobrutinib on Day 3 under fasted condition in period 2, followed by TF2 (Treatment C) on Day 5 under fed condition in period 3. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence 4: B-C-A | EXPERIMENTAL | Participants will receive single oral dose of TF2 (Treatment B) on Day 1 under fasted condition in period 1, followed by TF2 (Treatment C) on Day 3 under fed condition in period 2, followed by single oral dose of TF1 (Treatment A) evobrutinib on Day 5 under fasted condition in period 3. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence 5: C-A-B | EXPERIMENTAL | Participants will receive single oral dose of TF2 (Treatment C) on Day 1 under fed condition in period 1, followed by single oral dose of TF1 (Treatment A) evobrutinib on Day 3 under fasted condition in period 2, followed by single oral dose of TF2 (Treatment B) on Day 5 under fasted condition in period 3. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence 6: C-B-A | EXPERIMENTAL | Participants will receive single oral dose of TF2 (Treatment C) on Day 1 under fed condition in period 1, followed by single oral dose of TF2 (Treatment B) on Day 3 under fasted condition in period 2, followed by single oral dose of TF1 (Treatment A) evobrutinib on Day 5 under fasted condition in period 3. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence A, B, C, D | EXPERIMENTAL | Participant will receive single oral dose of evobrutinib after an overnight fast of at least 10 hours (Treatment A) for 3 days, followed by within 30 minutes after start of a light meal (Treatment B) for 2 days, followed by 1 hour prior to a low-fat meal (Treatment C) for 2 days, followed by 2 hours after start of low-fat meal (Treatment D) for 2 days. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence B, D, A, C | EXPERIMENTAL | Participant will receive single oral dose of evobrutinib within 30 minutes after start of a light meal (Treatment B) for 3 days, followed by 2 hours after start of a low-fat meal (Treatment D) for 2 days, followed by after an oversight fast of at least 10 hours (Treatment A) for 2 days, followed by 1 hour prior to a low-fat meal (Treatment C) for 2 days. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence C, A, D, B | EXPERIMENTAL | Participant will receive single oral dose of evobrutinib 1 hour prior to a low-fat meal (Treatment C) for 3 days, followed by after an oversight fast of at least 10 hours (Treatment A) for 2 days, followed by 2 hours after start of a low-fat meal (Treatment D) for 2 days followed by within 30 minutes after start of a light meal (Treatment B) for 2 days. There will be 48 hours washout period between each treatment period. |
| Evobrutinib: Treatment Sequence D, C, B, A | EXPERIMENTAL | Participant will receive single oral dose of evobrutinib 2 hours after start of a low-fat meal (Treatment D) for 3 days, followed by 1 hour prior to a low-fat meal (Treatment C) for 2 days, followed by within 30 minutes after start of a light meal (Treatment B) for 2 days, followed by after an overnight fast of at least 10 hours (Treatment A) for 2 days. There will be 48 hours washout period between each treatment period. |
| Evobrutinib | EXPERIMENTAL | - |
| Evobrutinib: Normal Renal Function | EXPERIMENTAL | Subjects with estimated glomerular filtration rate (eGFR) greater than or equal to (\>=) 90 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2) will receive a single oral dose of evobrutinib under fasting conditions. |
| Evobrutinib: Severe Renal Impairment | EXPERIMENTAL | Subjects with eGFR less than (\<) 30 mL/min/1.73 m\^2 will receive a single oral dose of evobrutinib under fasting conditions. |
| Evobrutinib: Moderate Renal Impairment | EXPERIMENTAL | Subjects with eGFR \>= to 30 mL/min/1.73 m\^2 and \< 60 mL/min/1.73 m\^2 will receive a single oral dose of evobrutinib under fasting conditions. |
| Evobrutinib: Mild Renal Impairment | EXPERIMENTAL | Subjects with eGFR \>= to 60 mL/min/1.73 m\^2 and \< 90 mL/min/1.73 m\^2 will receive a single oral dose of evobrutinib under fasting conditions. |
| Name | Type | Description |
|---|---|---|
| Evobrutinib | DRUG | Participants received a single oral dose of Evobrutinib 45 mg on Day 1 and Day 19 |
| Carbamazepine | DRUG | Participants received Carbamazepine 100 mg on Days 2 and 3, 200 mg on Days 4 and 5 and then 300 mg from Days 6 to 19 and were titrated back to 200 mg from Days 20 to 22 and 100 mg on Days 23 to 25 twice daily. |
Inclusion Criteria: * Type of Participant and Disease Characteristics * Had a body weight within 50.0 and 100.0 kg (kilogram) (inclusive) and Body Mass Index (BMI) within the range 19.0 and 30.0 kilogram per meter square (kg/m\^2) (inclusive) * Male: No contraception and barrier requirements were n...
Evobrutinib is an investigational small molecule being studied in healthy volunteers for early-stage clinical pharmacology trials, including absorption, metabolism, excretion, bioavailability, and drug-drug interaction studies. It is not approved for any disease and remains in Phase 1 clinical development.
Evobrutinib is being developed by Merck KGaA, a German multinational pharmaceutical company. The company's over-the-counter ticker is MKGAF. Merck KGaA is conducting Phase 1 clinical trials to evaluate the drug's pharmacokinetic properties in healthy participants.
Evobrutinib is in Phase 1 clinical development. All four completed trials were Phase 1 studies, and no later-phase trials have been reported. The drug remains investigational and has not received regulatory approval.
Evobrutinib has completed four Phase 1 trials: NCT03725072 (ADME study in healthy males), NCT03934502 (effect of meal composition on bioavailability), NCT04314024 (relative bioavailability of tablets), and NCT05248945 (drug-drug interaction with carbamazepine). All trials enrolled healthy volunteers and are completed.
Evobrutinib is not FDA approved. It is an investigational drug that has only been studied in Phase 1 clinical trials involving healthy volunteers. No efficacy trials in patients have been conducted, and the drug remains in early clinical development.