Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MK-4208, HS-10382
Embibatinib · 1 trial · 1 indication
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience a treatment emergent AE will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
Blood pressure will be measured after the participant has been at rest in a supine position for at least 10 minutes. Blood pressure and pulse measurements will be assessed with a completely automated device; manual techniques will be used only if an automated device is not available. Blood pressure measurements will be carried out before blood sample collections or at least 30 minutes after any blood draws.
Blood pressure will be measured after the participant has been at rest in a supine position for at least 10 minutes. Blood pressure and pulse measurements will be assessed with a completely automated device; manual techniques will be used only if an automated device is not available. Blood pressure measurements will be carried out before blood sample collections or at least 30 minutes after any blood draws.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with abnormal hematology-related AEs will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with abnormal chemistry-related AEs will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with abnormal urinalysis-related AEs will be reported.
During the 12-lead ECG collection participants will be instructed to lie supine for at least 10 minutes prior to ECG collection. During the collection, participants should be in a quiet setting, without distractions, and should refrain from talking or moving their arms or legs. All ECG acquisitions will be carried out before any blood sample collections or at least 30 minutes after any blood draws.
Blood samples will be collected to determine the AUC0-Last of Embibatinib.
Blood samples will be collected to determine the AUC0-inf of Embibatinib.
Blood samples will be collected to determine the AUCtau of Embibatinib.
Blood samples will be collected to determine the Cmax of Embibatinib.
Blood samples will be collected to determine the t1/2 of Embibatinib.
Blood samples will be collected to determine the Tmax of Embibatinib.
| Arm | Type | Description |
|---|---|---|
| Cohort 1: Single Ascending Dose (SAD) Escalation of Embibatinib Dose Level 1 | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 1 under fasted conditions on Day 1. |
| Cohort 2: SAD Escalation of Embibatinib Dose Level 2 | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 2 under fasted conditions on Day 1. |
| Cohort 3: SAD Escalation of Embibatinib Dose Level 3 and Food Effect | EXPERIMENTAL | On Period 1 Day 1, participants receive a single oral dose of Embibatinib Dose Level 3 under fasted conditions. On Period 2 Day 1, participants receive Embibatinib Dose Level 3 after a high-fat meal. |
| Cohort 4: SAD Escalation of Embibatinib Dose Level 4 | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 4 under fasted conditions on Day 1. |
| Cohort 5: SAD Escalation of Embibatinib Dose Level 5 | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 5 under fasted conditions on Day 1. |
| Cohort 6: SAD Escalation of Embibatinib Dose Level 7 | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 7 under fasted conditions on Day 1. |
| Cohort 7: Embibatinib Formulations with Rabeprazole 20 mg | EXPERIMENTAL | Participants in Cohort 7 are randomized to receive Embibatinib Formulation 1 or Formulation 2 at Dose Level 5 on Day 1. On Day 7, participants receive Embibatinib Formulation 2 or Formulation 1 at Dose Level 5. Participants also receive Rabeprazole 20 mg once daily on Days 10-13. On Day 14, participants will co-administer a single oral dose of Rabeprazole 20 mg with Embibatinib Formulation 1 Dose Level 5 at the same time. All participants receive treatment under fasted conditions. |
| Cohort 8: Embibatinib + Probe Substrate Cocktail-1 | EXPERIMENTAL | Per protocol, the probe substrate cocktail-1 consists of midazolam 2 mg, digoxin 0.25 mg, pravastatin 40 mg, montelukast 10 mg, and omeprazole 40 mg. On Day 1, participants receive a single oral dose of the probe substrate cocktail-1 under fasted conditions. On Day 5, participants receive a single oral dose of Embibatinib Dose Level 4 co-administered with a single oral dose of the probe substrate cocktail-1 taken at the same time under fasted conditions. On Day 9, participants receive a single oral dose of Embibatinib Dose Level 7 co-administered with a single oral dose of the probe substrate cocktail-1 taken at the same time under fasted conditions. |
| Cohort 9: Embibatinib Dose Level 5 + Rabeprazole 20 mg | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 5 on Day 1 under fasted conditions. On Days 4-7 participants will receive Rabeprazole 20 mg once daily under fasted conditions. On Day 8, under fasted conditions, participants co-administer a single oral dose of Embibatinib Dose Level 5 with a single oral dose of Rabeprazole 20 mg taken at the same time under fasted conditions. |
| Cohort 10: SAD Escalation of Embibatinib Dose Level 8 | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 8 under fasted conditions on Day 1. |
| Cohort 11: SAD Escalation of Embibatinib Dose Level 9 | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 9 under fasted conditions on Day 1. |
| Cohort 12: Embibatinib Dose Level 3 + Itraconazole 200 mg | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib at Dose Level 3 under nonfasted conditions on Day 1. On Day 8, participants will receive Itraconazole 200 mg twice daily after a standardized breakfast and evening snack. On Days 9-11, participants will take a single oral dose of Itraconazole 200 mg after a standardized meal. On Day 12, participants will take a single dose of Itraconazole 200mg after a standardized meal followed by Embibatinib Dose Level 3 taken an hour later. Participants will continue taking a single oral dose of Itraconazole 200 mg once daily after a standardized meal on Days 13-15. |
| Cohort 13: Multiple Ascending Dose (MAD) Escalation of Embibatinib Dose Level 4 | EXPERIMENTAL | Participants receive an oral dose of Embibatinib Dose Level 4 once daily from Day 1 to Day 13 under fasted conditions. |
| Cohort 14: Embibatinib Dose Level 5 + Probe Substrate Cocktail-2 | EXPERIMENTAL | Per protocol, the probe substrate cocktail-2 consists of midazolam 2 mg, warfarin 5 mg, and rosuvastatin 10 mg. Participants receive a single oral dose of the Probe Substrate Cocktail-2 on Day 1 under fasted conditions. On Days 9-15, participants receive a single oral dose of Embibatinib Dose Level 5 once daily under fasted conditions. On Day 16, participants receive a single oral dose of the Probe Substrate Cocktail-2 co-administered with Embibatinib Dose Level 5 taken at the same time under fasted conditions. On Days 17-21 participants receive Embibatinib Dose Level 5 as a single oral dose once daily under fasted conditions. |
| Cohort 15: Embibatinib Dose Level 8 + Probe Substrate Cocktail-2 | EXPERIMENTAL | Per protocol, the probe substrate cocktail-2 consists of midazolam 2 mg, warfarin 5 mg, and rosuvastatin 10 mg. Participants receive a single oral dose of the Probe Substrate Cocktail-2 on Day 1 under fasted conditions. On Days 9-15, participants receive a single oral dose of Embibatinib Dose Level 8 once daily under fasted conditions. On Day 16, participants receive a single oral dose of the Probe Substrate Cocktail-2 co-administered with Embibatinib Dose Level 8 taken at the same time under fasted conditions. On Days 17-21 participants receive Embibatinib Dose Level 8 as a single oral dose once daily under fasted conditions. |
| Cohort 16: Food Effect on Embibatinib Dose Level 8 Formulations with Rabeprazole 20 mg | EXPERIMENTAL | On Period 1 Day 1, participants receive a single oral dose of Embibatinib Formulation 3 Dose Level 8 (DL8). On Period 1 Day 7, participants receive a single oral dose of Embibatinib Formulation 4 DL8. On Period 1 Day 13, participants receive a single oral dose of Embibatinib Formulation 5 DL8. On Period 1 Day 19, participants receive a single oral dose of Embibatinib Formulation 6 DL8. All Period 1 treatments are administered under fasted conditions. Per protocol, following Period 1, one formulation is selected for Period 2. On Period 2 Day 1, participants receive a single oral dose of the selected Embibatinib formulation DL8 after a high-fat meal. On Period 2 Days 7-10, participants receive rabeprazole 20 mg once daily under fasted conditions. On Period 2 Day 11, participants receive the selected formulation of Embibatinib DL8 as a single oral dose, co-administered with the single oral dose of Rabeprazole 20 mg taken at the same time under fasted conditions. |
| Cohort 17: Food Effect on Embibatinib Dose Level 8 Selected Formulation with Rabeprazole 20 mg | EXPERIMENTAL | Per protocol, a formulation from Cohort 16 Period 1, different from the formulation selected for Cohort 16 Period 2, may be selected to evaluate the effects of food and rabeprazole 20 mg. On Day 1, participants receive a single oral dose of the selected formulation of Embibatinib Dose Level 8 under fasted conditions. On Day 7, participants receive a single oral dose of the selected formulation of Embibatinib Dose Level 8 after a high-fat meal. On Days 13-16, participants receive a single oral dose of rabeprazole 20 mg once daily. On Day 17, participants receive a single oral dose of the selected formulation of Embibatinib Dose Level 8 co-administered with a single oral dose of rabeprazole 20 mg taken at the same time under fasted conditions. |
| Cohort 18: Embibatinib Dose Level 8 + Bosentan 125 mg | EXPERIMENTAL | On Day 1, participants receive a single oral dose of Embibatinib Dose Level 8 under fasted conditions. Beginning on Day 8, participants receive an oral dose of Bosentan 125 mg twice daily. On Day 15, participants receive Embibatinib Dose Level 8 as a single oral dose co-administered with the morning dose of Bosentan 125 mg taken at the same time under fasted conditions; participants then receive the second daily dose of Bosentan 125 mg in the evening. Participants continue taking Bosentan 125 mg twice daily on Days 16-18. |
| Cohort 19: Embibatinib Dose Level 6 + Quinidine 300 mg | EXPERIMENTAL | Participants receive a single oral dose of Embibatinib Dose Level 6 on Day 1 under fasted conditions. Beginning on Day 6, participants receive an oral dose of Quinidine 300 mg three times daily. On Day 8, participants receive Embibatinib Dose Level 6 as a single oral dose co-administered with the morning final dose of Quinidine 300 mg taken at the same time under fasted conditions. |
| Name | Type | Description |
|---|---|---|
| Embibatinib | DRUG | Oral Tablet |
| Rabeprazole | DRUG | The United States commercially marketed 20 mg oral tablet formulation is being used in this trial. |
| Midazolam | DRUG | 2 mg oral syrup formulation administered as part of the probe substrate cocktail-1 and probe substrate cocktail-2. The United States commercially marketed formulation is being used in this trial. |
| Digoxin | DRUG | 0.25 mg oral tablet formulation administered as part of the probe substrate cocktail-1. The United States commercially marketed formulation is being used in this trial. |
| Pravastatin | DRUG | 40 mg oral tablet formulation administered as part of the probe substrate cocktail-1. The United States commercially marketed formulation is being used in this trial. |
| Montelukast | DRUG | 10 mg oral tablet formulation administered as part of the probe substrate cocktail-1. The United States commercially marketed formulation is being used in this trial. |
| Omeprazole | DRUG | 40 mg oral tablet formulation administered as part of the probe substrate cocktail-1. The United States commercially marketed formulation is being used in this trial. |
| Itraconazole | DRUG | The United States commercially marketed 200 mg oral capsule formulation is being used in this trial. |
| Warfarin | DRUG | 5 mg oral tablet formulation administered as part of the probe substrate cocktail-2. The United States commercially marketed formulation is being used in this trial. |
| Rosuvastatin | DRUG | 10 mg oral tablet formulation administered as part of the probe substrate cocktail-2. The United States commercially marketed formulation is being used in this trial. |
| Bosentan | DRUG | The Europe commercially marketed 125 mg oral tablet formulation is being used in this trial. |
| Quinidine | DRUG | The United States commercially marketed 300 mg oral tablet formulation is being used in this trial. |
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has body weight ≥48 kg (105.6 lbs) and body mass index within the range of 18.5 to 32 kg/m\^2 (inclusive) * Is in good health Exclusion Criteria: The main exclusion criteria include but are not limite...