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

NCT ID: NCT03826602

Last Updated: 2019-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-12
• Study Completion Date: 2019-03-15

Brief Summary

This study is being done to look at how tucatinib might affect the way another drug (metformin) works. It will look at healthy volunteers and how tucatinib affects how the body absorbs metformin. This will help us find out whether tucatinib is safe to give together with metformin. The study will also look at how tucatinib affects how the kidneys work.

Detailed Description

This is a single center, fixed-sequence, drug-drug interaction study to assess the effects of multiple oral doses of tucatinib on the pharmacokinetics of a single oral dose of metformin in healthy subjects. The primary objective of the study is to assess the effects of tucatinib on the single-dose PK of metformin. Secondary objectives of the study are to (1) assess the safety and tolerability of metformin when coadministered with tucatinib and (2) assess the effects of tucatinib on renal function using iohexol as glomerular filtration rate (GFR) marker.

Conditions

Drug-drug Interaction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tucatinib plus metformin

Tucatinib administered twice daily on Days 2-8. Metformin administered as a single dose on Days 1 and 8. Iohexol administered via IV push on Days 1 and 8

Group Type: EXPERIMENTAL

Tucatinib

Intervention Type: DRUG

150mg administered orally twice daily

Metformin

Intervention Type: DRUG

850mg administered orally

Iohexol

Intervention Type: DRUG

1500 mg administered intravenously (IV)

Interventions

Tucatinib

150mg administered orally twice daily

Intervention Type: DRUG

Metformin

850mg administered orally

Intervention Type: DRUG

Iohexol

1500 mg administered intravenously (IV)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy status, as defined by the absence of evidence of any clinically significant findings
• Males must agree to use a barrier method of birth control and not donate sperm during study plus 30 days after last dose of study drug
• Weight of ≥60kg
• Body mass index between 18.0 and 32.0 kg/m² (inclusive)
• Ability to abstain from alcohol-, caffeine-, and xanthine-containing food and beverages from 48 hours prior to admission through study discharge
• All nonregular medication (including over-the-counter medication, health supplements, and herbal remedies) must be stopped at least 28 days prior to admission

Exclusion Criteria

• Females who are of childbearing potential or lactating
• Males with female partners who are pregnant, lactating, or planning to become pregnant within 30 days of the study
• Use of any investigational drug or device within 30 days of study start
• Use of tobacco products within 21 days prior to admission
• Routine or chronic use of more than 3 grams of acetaminophen daily
• Strenuous activity, sunbathing, and contact sports within 72 hours prior to first admission and for the duration of the study
• Blood transfusion within 90 days of study drug administration
• History of alcoholism or drug abuse within 2 years
• History of alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male subjects
• History of donation of more than 450 mL of blood within 60 days prior to dosing, or planned donation before 30 days have elapsed since intake of study drug
• Plasma or platelet donation within 7 days of initial study drug administration
• Positive screening test for Hepatitis B, Hepatitis C, or HIV 1 or 2 (human immunodeficiency virus)
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis
• Renal disease or dysfunction as suggested by serum creatinine levels or abnormal creatinine clearance

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Seagen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

JoAl Mayor, PharmD, BCOP

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

Pharmaceutical Research Associates

Salt Lake City, Utah, United States

Countries

United States

References

Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. Epub 2024 Oct 5.

Reference Type: DERIVED

PMID: 39368039 (View on PubMed)

Other Identifiers

SGNTUC-020

Identifier Type: -

Identifier Source: org_study_id