NCT01596647

Pharmacokinetic Drug-drug Interaction Study of Dovitinib (TKI258) in Patients With Advanced Solid Tumors

A Phase I, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of TKI258 on the Pharmacokinetics of Caffeine, Diclofenac, Omeprazole and Midazolam Administered as a Four-drug Cocktail in Patients With Advanced Solid Tumors, Excluding Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 39 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multi-center, open-label, phase I study to assess the effects of dovitinib (TKI258) on the pharmacokinetics of a cocktail of caffeine, diclofenac, omeprazole and midazolam in patients with advanced solid tumors, excluding breast cancer. The aim of this study is to evaluate the potential effect of dovitinib (TKI258) on the metabolism of the probe drugs caffeine, diclofenac, omeprazole and midazolam, which are metabolized by CYP1A2, CYP2C9, CYP2C19 and CYP3A4 respectively (Cytochrome P450 isoenzyme), comparing the single-dose pharmacokinetics (AUCtlast, AUCinf and Cmax parameters) of each of the individual probe drug co-administered with and without multiple dose of dovitinib (TKI258) 500 mg under a 5 days on / 2 days off dose schedule. The study foresees two treatment phases: DDI (drug-drug interaction) followed by post-DDI. During the DDI phase patients receive treatment with the probe drug cocktail and dovitinib (TKI258). During the post-DDI phase patients may continue to receive treatment with dovitinib (TKI258) until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.

Conditions

• Advanced Solid Tumors, Excluding Breast Cancer

Interventions

Type	Name	Description
DRUG	caffeine	single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
DRUG	diclofenac	single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
DRUG	omeprazole	single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
DRUG	midazolam	single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
DRUG	TKI258	dovitinib, 5 days on / 2 days off dose schedule

Timeline

• Start date: 2012-05-01
• Primary completion: 2014-07-01
• Completion: 2014-07-01
• First posted: 2012-05-11
• Last updated: 2020-12-21

Locations

5 sites across 1 country: United States