NCT01517399

Drug-drug Interaction Study of Tivantinib (ARQ 197) With Omeprazole, S-warfarin, Caffeine, Midazolam, and Digoxin in Cancer Subjects

A Phase 1, Open-Label, Single-Sequence Crossover Study Assessing the Effect of Tivantinib (ARQ 197) on the Pharmacokinetics of Omeprazole/S-Warfarin/Caffeine/Midazolam and Digoxin in Cancer Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Daiichi Sankyo · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the effects of tivantinib on the pharmacokinetics of omeprazole, s-warfarin, caffein, midazolam, or digoxin in patients with cancer.

Detailed description

Nonclinical studies have indicated that tivantinib (parent molecule) has the potential to inhibit CYP3A4 (\[I\]/Ki=0.15, midazolam as substrate), CYP2C19 (\[I\]/Ki=0.98), CYP2C9 (\[I\]/Ki=0.44), and CYP1A (\[I\]/Ki=0.37), and the efflux transporter P glycoprotein (P-gp) (I2/IC50=82) at the clinical concentrations being studied in the Phase 3 development program. In addition, tivantinib has major circulating plasma metabolite(s) which also have been shown in nonclinical studies to exhibit similar CYP inhibition potential. The results of this study will evaluate the potential of tivantinib to influence the pharmacokinetics of CYP3A4/CYP2C19/CYP2C9/CYP1A and/or P-gp substrates, and help to provide the guidance to clinicians on co-administration of tivantinib with drugs metabolized by CYP3A4/CYP2C19/CYP2C9/ CYP1A and/or transported by P-gp.

Conditions

• Solid Tumors

Interventions

Type	Name	Description
DRUG	tivantinib	three oral 120 mg tablets administered twice a day
DRUG	omeprazole	One 40 mg oral capsule once alone and once again with tivantinib
DRUG	s-warfarin	One 10 mg oral tablet once alone and once again with tivantinib
DRUG	caffeine	One 200 mg oral tablet once alone and once again with tivantinib
DIETARY_SUPPLEMENT	vitamin K	One oral 5 mg tablet on multiple days when and around warfarin administration
DRUG	digoxin	One oral 0.25 mg tablet once alone and once again with tivantinib
DRUG	midazolam	Intravenous 1.5 mg dose once alone and once again with tivantinib

Timeline

• Start date: 2011-12-01
• Primary completion: 2013-08-01
• Completion: 2013-09-01
• First posted: 2012-01-25
• Last updated: 2019-02-12

Locations

1 site across 1 country: United States