A Study to Compare the Relative Bioavailability of Brigatinib When Swallowed as a Solution Versus When Swallowed as a Tablet in Healthy Adults

A Phase 1, Open-Label, Randomized, Single-Dose, 2-Period, Crossover Study to Evaluate the Relative Bioavailability of Brigatinib Administered as an Oral Solution Versus an Immediate-Release Tablet in Adult Healthy Subjects

The main aim of this study is to compare the amount of brigatinib in the blood of healthy adults after they have swallowed one dose either as a solution or as a tablet.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Brigatinib; Drug: Brigatinib

Detailed Description

The drug being tested in this study is called brigatinib. Brigatinib is being tested to assess its relative bioavailability when administered as an oral solution versus as an immediate-release tablet in healthy participants.

The study will enroll approximately 12 participants. Participants will be randomly assigned to one of the treatment sequences:

• Sequence 1: Treatment A followed by Treatment B
• Sequence 2: Treatment B followed by Treatment A wherein Treatment A is a 90 mg oral solution dose and Treatment B is a 90 mg tablet dose.

There will be a washout period of at least 14 days between brigatinib administration in each study period. The follow-up contact will occur 14 (±2) days post the last dose of study drug.

This single-center trial will be conducted in the United States. The overall study duration is approximately 56 days.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Continuous nonsmoker who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study.
2. Body mass index (BMI) ≥18.0 and ˂32.0 kilograms per meters squared (kg/m^2) at screening.
3. Pulse rate between 60 and 100 beats per minute (bpm) and a blood pressure between 90 to 140 millimeters of mercury (mmHg) systolic and 40 to 90 mmHg diastolic at screening and prior to dosing of Period 1.
4. Creatine phosphokinase is ≤1.1x upper limit of normal [ULN]; lipase, amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, glucose, and activated partial thromboplastin time (aPTT) are ≤ULN at screening and check-in of Period 1.

Exclusion Criteria:

1. Any history of major surgery.
2. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.
3. Unable to refrain from or anticipates the use of any drug, including prescription and nonprescription medications, herbal remedies, or vitamin supplements within 28 days prior to the first dosing and throughout the study.
4. Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B surface Antigen (HBsAg), or Hepatitis C Virus (HCV).
5. Positive coronavirus disease 2019 (COVID-19) results at first check-in.
6. Donation of blood or significant blood loss within 56 days prior to the first dosing.
7. Plasma donation within 7 days prior to the first dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AB; Participants received single dose of brigatinib 90 milligram (mg) as an oral solution in a fasted state on Day 1 of Period 1 (Treatment A) followed by single dose of brigatinib 90 mg as an immediate-release tablet in a fasted state on Day 1 of Period 2 (Treatment B). A washout period of at least 14 days was maintained between brigatinib administration in Period 1 and 2.	Drug: Brigatinib; Brigatinib tablet; Other Names: ALUNBRIG®; Drug: Brigatinib; Brigatinib oral solution
Experimental: Sequence BA; Participants received single dose of brigatinib 90 mg as an immediate-release tablet in a fasted state on Day 1 of Period 1 (Treatment B) followed by single dose of brigatinib 90 mg as an oral solution in a fasted state on Day 1 of Period 2 (Treatment A). A washout period of at least 14 days was maintained between brigatinib administration in Period 1 and 2.	Drug: Brigatinib; Brigatinib tablet; Other Names: ALUNBRIG®; Drug: Brigatinib; Brigatinib oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax: Maximum Observed Plasma Concentration for Brigatinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 120 and 168 hours post-dose
AUClast: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration for Brigatinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 120 and 168 hours post-dose
AUCinf: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity for Brigatinib	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 120 and 168 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant who had signed informed consent form (ICF) to participate in a study. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an adverse event that was starting or worsening at the time of or after the first dose of brigatinib administered in the study. An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly or is an important medical event.	From first dose of the study drug up to Day 31

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click this link.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Actual): February 17, 2024
• Study Completion (Actual): February 17, 2024

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: Brigatinib-1004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No