Micronutrients

All Drugs and Chemicals

Central Nervous System Stimulants

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Anti-Arrhythmia Agents

Cardiotonic Agents

Anticoagulants

Gastrointestinal Agents

Coagulants

Other Dietary Supplements

Vitamins

Caffeine

Midazolam

Digoxin

Warfarin

Omeprazole

Vitamin K

Trace Elements

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Phosphodiesterase Inhibitors

Enzyme Inhibitors

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Protective Agents

Antifibrinolytic Agents

Hemostatics

Menadione

Menaquinone

Naphthoquinone

Phylloquinone

All drugs except vitamin K will be administered as a single dose once by itself as a reference treatment and once with tivantinib

three oral 120 mg tablets administered twice a day

tivantinib

One 40 mg oral capsule once alone and once again with tivantinib

omeprazole

One 10 mg oral tablet once alone and once again with tivantinib

s-warfarin

One 200 mg oral tablet once alone and once again with tivantinib

caffeine

One oral 5 mg tablet on multiple days when and around warfarin administration

vitamin K

One oral 0.25 mg tablet once alone and once again with tivantinib

digoxin

Intravenous 1.5 mg dose once alone and once again with tivantinib

midazolam

Hamim Zahir, BPharm, PhD

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.

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.

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

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

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.

Maximum observed concentration in plasma \[Cmax\] when omeprazole, warfarin, caffeine, midazolam and digoxin are administered alone or in combination with tivantinib.

Maximum observed concentration in plasma \[Tmax\] when omeprazole, warfarin, caffeine, midazolam and digoxin are administered alone or in combination with tivantinib.

Apparent oral clearance \[CL/F\] when omeprazole, warfarin, caffeine, midazolam and digoxin are administered alone or in combination with tivantinib.

Apparent volume of distribution \[V/F\] when omeprazole, warfarin, caffeine, midazolam and digoxin are administered alone or in combination with tivantinib.

Medpace, Inc.

Daiichi Sankyo

Antineoplastic Agents

Poly(ADP-ribose) Polymerase Inhibitors

Rucaparib

Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib

The purpose of this study is to assess pharmacokinetic concentrations of multiple probes alone followed by assessment of the same drug pharmacokinetic concentrations when the patient has steady-state exposure to rucaparib followed by cycle-by-cycle treatment with rucaparib continuing until disease progression or other reason for discontinuation.

This is a Phase 1, open-label, sequential, drug-drug-interaction (DDI) study in patients with advanced solid tumors. The study will consist of 2 parts: a DDI part (Part I) and a rucaparib treatment part (Part II).

In Part I, the PK of cytochrome P450 (CYP) cocktail probes: caffeine, S-warfarin, omeprazole, and midazolam and a P-glycoprotein probe (digoxin) will be assessed with and without rucaparib treatment. Patients will receive single doses of CYP drug cocktail (caffeine, warfarin, omeprazole, and midazolam) on Day 1 and Day 12, and single doses of digoxin on Day 2 and Day 13. Continuous treatment with 600 mg rucaparib twice daily (BID) will start on Day 5 and will last until at least Day 16 of Part I.

In Part II, the treatment with rucaparib in 28-day cycles will continue until progression of disease, unacceptable toxicity, or other reason for discontinuation.

Pharmacokinetic Drug-Drug Interaction Study of Rucaparib

A Phase 1, Open-label, Multiple-probe Drug-drug Interaction Study to Determine the Effect of Rucaparib on Pharmacokinetics of Caffeine, S-Warfarin, Omeprazole, Midazolam, and Digoxin in Patients With Advanced Solid Tumors

28 day cycles with response evaluation every 8 weeks(±7 days) until week 24 thereafter every 12 weeks (±14 days)

Area under the concentration-time curve (AUC) up to time t, where t is the last time point with concentrations above the lower limit of quantitation \[AUC0-last \]

Area Under the Curve, from time zero up to infinity with extrapolation of the terminal phase \[AUC0-inf\]

Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications

Maximum plasma concentration during a dosing interval at steady-state \[Cmax,ss\]

Time to attain maximum plasma concentration at steady-state \[tmax,ss\]

Area Under the Curve over a dosing interval τ at steady-state \[AUCτ,ss\]

Time to attain maximum plasma concentration \[tmax\]

Apparent volume of distribution during terminal phase \[Vz/F\]

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Drug-drug Interaction Study of Tivantinib (ARQ 197) With Omeprazole, S-warfarin, Caffeine, Midazolam, and Digoxin in Cancer Subjects	NCT01517399	Solid Tumors	tivantinib omeprazole s-warfarin caffeine vitamin K digoxin midazolam	18 Years -	Daiichi Sankyo
Pharmacokinetic Drug-Drug Interaction Study of Rucaparib	NCT02740712	Neoplasms	Caffeine Warfarin Omeprazole Midazolam digoxin Vitamin K Rucaparib	18 Years -	pharmaand GmbH

Spots Global Cancer Trial Database for vitamin k

Every month we try and update this database with for vitamin k cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for vitamin k

Every month we try and update this database with for vitamin k cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for vitamin k cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.