NCT03723395

A Drug-Drug Interaction Study in Healthy Volunteers of the Effects of Tucatinib

A Phase 1, Open-Label, Fixed-sequence, 5-part, Drug-drug Interaction Study of Tucatinib to Evaluate the Effects of CYP3A4 and CYP2C8 Inhibition and Induction on the Pharmacokinetics of Tucatinib and to Evaluate the Effects of Tucatinib on the Pharmacokinetics of Substrates of CYP3A4, CYP2C8, CYP2C9, and P-glycoprotein in Healthy Male and Female Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 116 (actual)
• Sponsor: Seagen Inc. · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This study is being done to look at how tucatinib could affect the way other drugs work. This study will look at healthy volunteers and how tucatinib affects their liver enzymes. Liver enzymes can change how drugs work in the body. There are 5 parts to this study. Parts A and C are looking at how the body breaks down tucatinib when there are lower levels of certain liver enzymes. Part B is looking at how the body breaks down tucatinib when there are high levels of certain liver and stomach enzymes. Parts D and E are looking at how tucatinib could change the levels of some liver and stomach enzymes in the body. This will help us know more about how tucatinib should be given to patients.

Detailed description

This is a fixed-sequence, drug-drug interaction study of tucatinib conducted in 5 parts in healthy subjects. Part A will evaluate the effect of the strong CYP3A4 inhibitor itraconazole on the pharmacokinetics (PK) of tucatinib. Part B will evaluate the effect of rifampin, a strong inducer of CYP3A4 and CYP2C8, on the PK of tucatinib. Part C will evaluate the effect of the strong CYP2C8 inhibitor gemfibrozil on the PK of tucatinib. Part D will evaluate the effects of tucatinib on the PK of substrate probes of the metabolizing enzymes CYP2C8 (repaglinide), CYP2C9 (tolbutamide), and CYP3A4 (midazolam). Part E will evaluate the effect of tucatinib on the PK of a substrate probe of the transporter P-gp (digoxin). Parts A, B, C, D, and E of the study are independent of one another and do not need to be conducted in a particular order.

Conditions

• Drug-drug Interaction

Interventions

Type	Name	Description
DRUG	tucatinib	300mg dose, orally administered
DRUG	itraconazole	200mg dose
DRUG	rifampin	600mg dose
DRUG	gemfibrozil	600mg tablets
DRUG	repaglinide	1mg dose
DRUG	tolbutamide	500mg dose
DRUG	midazolam	2mg dose
DRUG	digoxin	0.5 mg dose

Timeline

• Start date: 2018-09-17
• Primary completion: 2018-12-21
• Completion: 2018-12-28
• First posted: 2018-10-29
• Last updated: 2019-12-18

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study