Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
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.
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.
Interventions
DRUGBrigatinib
Brigatinib oral solution
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From first dose of the study drug up to Day 31 | 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. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 20 December 2023 to 17 February 2024.
Pre-assignment details
A total of 12 participants entered the study and were randomized in a 1:1 ratio to one of the treatment sequences: Treatment A followed by Treatment B (AB) or Treatment B followed by Treatment A (BA).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| 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. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Sequence BA | Total | Sequence AB |
|---|---|---|---|
| Age, Continuous | 39.3 years STANDARD_DEVIATION 8.5 | 42.3 years STANDARD_DEVIATION 9.76 | 45.2 years STANDARD_DEVIATION 10.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 12 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 2 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
AUCinf: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity for Brigatinib
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 120 and 168 hours post-dose
Population: The PK analysis set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Brigatinib 90 mg Oral Solution | AUCinf: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity for Brigatinib | 7373 ng*h/mL | Geometric Coefficient of Variation 39.5 |
| Treatment B: Brigatinib 90 mg Tablet | AUCinf: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity for Brigatinib | 7693 ng*h/mL | Geometric Coefficient of Variation 41 |
90% CI: [88.81, 103.42]
Primary
AUClast: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration for Brigatinib
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 120 and 168 hours post-dose
Population: The PK analysis set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Brigatinib 90 mg Oral Solution | AUClast: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration for Brigatinib | 6930 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 43.4 |
| Treatment B: Brigatinib 90 mg Tablet | AUClast: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration for Brigatinib | 7219 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 43.6 |
90% CI: [88.48, 104.16]
Primary
Cmax: Maximum Observed Plasma Concentration for Brigatinib
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 120 and 168 hours post-dose
Population: The pharmacokinetic (PK) analysis set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Brigatinib 90 mg Oral Solution | Cmax: Maximum Observed Plasma Concentration for Brigatinib | 366.6 nanogram per millliliter (ng/mL) | Geometric Coefficient of Variation 53.2 |
| Treatment B: Brigatinib 90 mg Tablet | Cmax: Maximum Observed Plasma Concentration for Brigatinib | 397.6 nanogram per millliliter (ng/mL) | Geometric Coefficient of Variation 49.7 |
90% CI: [86.98, 97.74]
Secondary
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.
Time frame: From first dose of the study drug up to Day 31
Population: The safety analysis set included all the participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Brigatinib 90 mg Oral Solution | Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 2 Participants |
| Treatment A: Brigatinib 90 mg Oral Solution | Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| Treatment B: Brigatinib 90 mg Tablet | Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 2 Participants |
| Treatment B: Brigatinib 90 mg Tablet | Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |