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

NCT03723395 | Completed Phase 1 FDA Drug

• 1 other identifier: ONT-380-012
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Drug-drug Interaction

Outcome Measures

Primary Outcomes (9)

• Area under the concentration-time curve (AUC) from time 0 to infinity

  PK parameters for tucatinib (Parts A, B, and C); repaglinide and its M4 metabolite (Part D), tolbutamide and its 4-hydroxytolbutamide metabolite (Part D), midazolam and its 1-hydroxymidazolam metabolite (Part D), and digoxin (Part E)

  Up to 22 days

• AUC from time 0 to the time of the last quantifiable concentration

  PK parameters for tucatinib (Parts A, B, and C); repaglinide and its M4 metabolite (Part D), tolbutamide and its 4-hydroxytolbutamide metabolite (Part D), midazolam and its 1-hydroxymidazolam metabolite (Part D), and digoxin (Part E)

  Up to 22 days

• Percentage extrapolation in AUC

  PK parameters for tucatinib (Parts A, B, and C); repaglinide and its M4 metabolite (Part D), tolbutamide and its 4-hydroxytolbutamide metabolite (Part D), midazolam and its 1-hydroxymidazolam metabolite (Part D), and digoxin (Part E)

  Up to 22 days

• Maximum observed concentration

  PK parameters for tucatinib (Parts A, B, and C); repaglinide and its M4 metabolite (Part D), tolbutamide and its 4-hydroxytolbutamide metabolite (Part D), midazolam and its 1-hydroxymidazolam metabolite (Part D), and digoxin (Part E)

  Up to 22 days

• Time of maximum observed concentration

  PK parameters for tucatinib (Parts A, B, and C); repaglinide and its M4 metabolite (Part D), tolbutamide and its 4-hydroxytolbutamide metabolite (Part D), midazolam and its 1-hydroxymidazolam metabolite (Part D), and digoxin (Part E)

  Up to 22 days

• Apparent terminal elimination half-life

  PK parameters for tucatinib (Parts A, B, and C); repaglinide and its M4 metabolite (Part D), tolbutamide and its 4-hydroxytolbutamide metabolite (Part D), midazolam and its 1-hydroxymidazolam metabolite (Part D), and digoxin (Part E)

  Up to 22 days

• Apparent total clearance

  PK parameters for tucatinib (Parts A, B, and C); repaglinide (Part D), tolbutamide (Part D), midazolam (Part D), and digoxin (Part E).

  Up to 22 days

• Apparent volume of distribution

  PK parameters for tucatinib (Parts A, B, and C); repaglinide (Part D), tolbutamide (Part D), midazolam (Part D), and digoxin (Part E).

  Up to 22 days

• Metabolite-to-parent ratio based on AUC

  PK parameters for M4 metabolite, 4-hydroxytolbutamide metabolite, and 1-hydroxymidazolam metabolite (Part D only)

  Up to 22 days

Secondary Outcomes (21)

• Incidence of adverse events (AEs)

  Up to 58 days

• Incidence of laboratory abnormalities

  Up to 58 days

• 12-lead electrocardiogram (ECG) assessment

  Up to 58 days

• Vital signs measurements

  Up to 58 days

• Vital signs measurements

  Up to 58 days

Study Arms (5)

Part A

EXPERIMENTAL

Tucatinib plus Itraconazole

Drug: tucatinib; Drug: itraconazole

Part B

EXPERIMENTAL

Tucatinib plus Rifampin

Drug: tucatinib; Drug: rifampin

Part C

EXPERIMENTAL

Tucatinib plus Gemfibrozil

Drug: tucatinib; Drug: gemfibrozil

Part D

EXPERIMENTAL

Tucatinib plus Repaglinide plus Tolbutamide plus Midazolam

Drug: tucatinib; Drug: repaglinide; Drug: tolbutamide; Drug: midazolam

Part E

EXPERIMENTAL

Tucatinib plus Digoxin

Drug: tucatinib; Drug: digoxin

Interventions

tucatinib DRUG

300mg dose, orally administered

Part A; Part B; Part C; Part D; Part E

itraconazole DRUG

200mg dose

Part A

rifampin DRUG

600mg dose

Part B

gemfibrozil DRUG

600mg tablets

Part C

repaglinide DRUG

1mg dose

Part D

tolbutamide DRUG

500mg dose

Part D

midazolam DRUG

2mg dose

Part D

digoxin DRUG

0.5 mg dose

Part E

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) between 18 and 32 kg/m\^2
• In good health, determined be no clinically significant findings from medical history, physical examination, and screening evaluations
• Female subjects must be of nonchildbearing potential
• Male subjects must agree to use contraception or must be surgically sterile for at least 90 days prior to enrollment
• Able to understand and sign informed consent form

You may not qualify if:

• Any condition affecting drug absorption (including stomach or intestinal surgery)
• Significant history of metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder
• History of hypersensitivity, intolerance, or allergy to any drug compounds, food, or other substance (unless approved by Investigator)
• Participation in a clinical study involving an investigational drug within the past 30 days
• Use or intend to any prescription medications within 28 days prior to check in
• Use of tobacco- or nicotine-containing products within 28 days prior to check in
• History of hyperbilirubinemia
• History of alcoholism or drug abuse within 2 years
• History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects
• Positive hepatitis panel and/or positive human immunodeficiency virus (HIV) test

Sponsors & Collaborators

• Seagen Inc.: lead

Study Sites (2)

Covance Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

Covance Clinical Research Unit

Dallas, Texas, 75247, United States

Location

Related Publications (2)

• 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

• Topletz-Erickson A, Lee A, Rustia EL, Sun H, Mayor JG, Abdulrasool LI, Walker L, Endres CJ. Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteers. Clin Pharmacokinet. 2022 Oct;61(10):1417-1426. doi: 10.1007/s40262-022-01144-z. Epub 2022 Aug 6.

  PMID: 35931943 DERIVED

MeSH Terms

Interventions

tucatinib; Itraconazole; Rifampin; Gemfibrozil; repaglinide; Tolbutamide; Midazolam; Digoxin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Pentanoic Acids; Valerates; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Volatile; Fatty Acids; Lipids; Benzenesulfonamides; Sulfonamides; Amides; Sulfonylurea Compounds; Urea; Sulfones; Sulfur Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Glycosides; Carbohydrates

Study Officials

• Alex Vo, PhD

  Seagen Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 29, 2018
• Study Start: September 17, 2018
• Primary Completion: December 21, 2018
• Study Completion: December 28, 2018
• Last Updated: December 18, 2019

Record last verified: 2019-12

Locations

US (2)