Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Tivantinib · 3 trials · 4 indications
The following pharmacokinetic parameters will be determined: population estimates of apparent total clearance (CL/F), apparent volume of distribution (V/F), area under the concentration-time curve during the dosing interval (AUCtau), and maximum concentration (Cmax) during the dosing interval.
Triplicate ECG measurements of the QTc interval will be taken at Screening (4 sets each 1 hour apart) and pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 2, and 5 (+3 days)
Parameters of S-warfarin/caffeine/midazolam and digoxin (area under the concentration-time curve from time 0 to the last quantifiable concentration \[AUC last\] and area under the curve from time of dosing extrapolated to infinity \[AUC 0-inf\]) when warfarin/caffeine/midazolam and digoxin are administered alone or in combination with tivantinib
The ratios of omeprazole exposures vs. 5-hydroxyomeprazole exposures in terms of AUC last and AUC 0-inf when omeprazole is administered alone or in combination with tivantinib.
| Arm | Type | Description |
|---|---|---|
| Group 1 - Normal hepatic function | EXPERIMENTAL | Subjects with normal hepatic function |
| Group 2 - Mild hepatic impairment | EXPERIMENTAL | Subjects with mild hepatic impairment by Child-Pugh classification scores |
| Group 3 - Moderate hepatic impairment | EXPERIMENTAL | Subjects with moderate hepatic impairment by Child-Pugh classification scores |
| Group 4 - Severe hepatic impairment | EXPERIMENTAL | Subjects with severe hepatic impairment by Child-Pugh classification scores |
| Placebo | PLACEBO_COMPARATOR | Placebo tablet administered with a meal twice a day on Day 1 |
| Tivantinib | EXPERIMENTAL | 3 tivantinib tablets 120 mg administered twice daily with a meal starting on Day 2 |
| Test drug administration | OTHER | All drugs except vitamin K will be administered as a single dose once by itself as a reference treatment and once with tivantinib |
| Name | Type | Description |
|---|---|---|
| Tivantinib | DRUG | Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 360 mg twice daily in the extension phase. |
| Placebo | DRUG | Placebo tablet administered with a meal twice a day on Day 1 |
| omeprazole | DRUG | One 40 mg oral capsule once alone and once again with tivantinib |
| s-warfarin | DRUG | One 10 mg oral tablet once alone and once again with tivantinib |
| caffeine | DRUG | One 200 mg oral tablet once alone and once again with tivantinib |
| vitamin K | DIETARY_SUPPLEMENT | One oral 5 mg tablet on multiple days when and around warfarin administration |
| digoxin | DRUG | One oral 0.25 mg tablet once alone and once again with tivantinib |
| midazolam | DRUG | Intravenous 1.5 mg dose once alone and once again with tivantinib |
Inclusion Criteria: 1. Subjects must have histologically or cytologically confirmed advanced solid tumor. However, Hepatocellular Carcinoma (HCC) subjects are allowed without histological confirmation as long as there is radiological diagnosis as per standard criteria 2. Male or female ≥18 years of...