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

NCT03826602 | Completed Phase 1 FDA Drug

• 1 other identifier: SGNTUC-020
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug-drug Interaction

Outcome Measures

Primary Outcomes (7)

• Maximum observed plasma concentration (Cmax) of metformin

  Up to 9 days

• Time to maximum observed plasma concentration (tmax) of metformin

  Up to 9 days

• Half-life (t1/2) of metformin

  Up to 9 days

• Area under the plasma concentration-time curve from time 0 to the last available measurement (AUC0-last) of metformin

  Up to 9 days

• Area under the plasma concentration time curve to time 0 extrapolated to infinity (AUC0-inf) of metformin

  Up to 9 days

• Apparent volume of distribution (V2/F) of metformin

  Up to 9 days

• Oral clearance (CL/F) of metformin

  Up to 9 days

Secondary Outcomes (2)

• Incidence of adverse events (as assessed by AE assessments, clinical laboratory tests, physical examinations, vital signs measurements, and 12-lead electrocardiogram)

  Up to 16 days

• Glomerular Filtration Rate (GFR) as measured by iohexol plasma clearance

  Up to 8 days

Study Arms (1)

Tucatinib plus metformin

EXPERIMENTAL

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

Drug: Tucatinib; Drug: Metformin; Drug: Iohexol

Interventions

Tucatinib DRUG

150mg administered orally twice daily

Tucatinib plus metformin

Metformin DRUG

850mg administered orally

Tucatinib plus metformin

Iohexol DRUG

1500 mg administered intravenously (IV)

Tucatinib plus metformin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seagen Inc.: lead

Study Sites (1)

Pharmaceutical Research Associates

Salt Lake City, Utah, 84107, United States

Location

Related Publications (1)

• 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.

  PMID: 39368039 DERIVED

MeSH Terms

Interventions

tucatinib; Metformin; Iohexol

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Triiodobenzoic Acids; Iodobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• JoAl Mayor, PharmD, BCOP

  Seagen Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2019
• First Posted: February 1, 2019
• Study Start: February 12, 2019
• Primary Completion: March 8, 2019
• Study Completion: March 15, 2019
• Last Updated: March 27, 2019

Record last verified: 2019-03

Locations

US (1)