A Study of TAK-227 in Healthy Adults

A Randomized, Open-label, Single-dose, Three-way Crossover Evaluation of the Effect of Food on the Pharmacokinetics, Safety, and Tolerability of TAK-227 in Healthy Adult Participants

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05818956

Enrollment

Registered

2023-04-19

Start date

2023-05-25

Completion date

2023-06-26

Last updated

2024-08-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Brief summary

The main aim of this study is to test the effects of food consumption with sponsor compound TAK-227 in healthy participants. The study will also measure side effects, and to check how much TAK-227 stays in the blood over time to work out the best dose.

Detailed description

The drug being tested in this study is called TAK-227. This study will assess the effect of food on single-dose of TAK-227 in healthy participants. The study will enroll approximately 24 participants. A single dose of 50 milligram (mg) TAK-227 will be administered orally under one of 3 different feeding conditions. * Fasting (Treatment A), * Fed following a high-fat or high-calorie meal prior to dosing (Treatment B), and * Fed following a high-fat or high-calorie meal after dosing (Treatment C) Participants will be randomly assigned to 1 of the 6 treatments sequences based on the 3 feeding conditions. * Sequence 1: (Treatment A + Treatment B + Treatment C) * Sequence 2: (Treatment B + Treatment C + Treatment A) * Sequence 3: (Treatment C + Treatment A + Treatment B) * Sequence 4: (Treatment A + Treatment C + Treatment B) * Sequence 5: (Treatment B + Treatment A + Treatment C) * Sequence 6: (Treatment C + Treatment B + Treatment A) All participants will receive all 6 treatment regimens. This is a single-center trial. Participants will be followed up for up to 7 days after the last dose of study drug for a follow-up assessment. The overall time to participate in this study is approximately 40 days including screening period and follow-up period.

Interventions

DRUGTAK-227

TAK-227 capsules.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

Participants must fulfill the following inclusion criteria to be eligible for participation in the study: * Body mass index (BMI) greater than or equal to (\>=) 18 and less than or equal to (\<=) 32.0 kilogram per square meter (kg/m\^2) at screening visit. * Continuous non-smoker who has not used nicotine and tobacco containing products for at least 3 months prior to the first dosing based on participant self-reporting.

Exclusion criteria

Participants must not be enrolled in the study if they meet any of the following criteria: * Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. * Drink alcohol in excess of 21 units per week for males or 14 units per week for females, with one unit equal to (=) 150 milliliter (mL) of wine or 360 mL of beer or 45 mL of 45 percent (%) alcohol. * Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). * Unable to refrain from or anticipates the use of: * Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study. Medication listed as part of acceptable birth control methods will be allowed. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration. Hormone replacement therapy will also be allowed. * Any drugs known to be significant inducers or inhibitors of Cytochrome P450 (CYP)3A4 enzymes and/or P-glycoprotein (gp), including St. John's Wort, within 28 days prior to the first dosing and throughout the study. Appropriate sources (example, Flockhart Table TM) will be consulted to confirm lack of pharmacokinetic (PK)/pharmacodynamics interaction with study drug. * Chronic use of non-steroidal anti-inflammatory (define as more that 7 days of use) within 2 weeks prior to screening and throughout the study. * Donation of blood or significant blood loss within 56 days prior to the first dosing. * Plasma donation within 7 days prior to the first dosing.

Design outcomes

Primary

Measure	Time frame
Cmax: Maximum Observed Plasma Concentration for TAK-227	Day 1 pre-dose and at multiple time points (up to 36 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-227	Day 1 pre-dose and at multiple time points (up to 36 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-227	Day 1 pre-dose and at multiple time points (up to 36 hours) post-dose

Secondary

Measure	Time frame	Description
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values	Baseline to Day 13	Vital signs included body temperature (oral or tympanic measurement), respiratory rate, blood pressure \[systolic blood pressure (SBP) and diastolic blood pressure (DBP)\], and pulse (beats per minute). The clinically significant change assessment was based on investigator's judgment. Number of participants with clinically significant change from baseline in vital signs values were reported.
Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiograms (ECG) Values	Baseline to Day 13	ECGs was performed with participants in a supine position. All ECG tracings were reviewed by the investigator or designee. Number of participants with clinically significant change from baseline in ECG values were reported.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	From start of study drug administration up to 7 days after the last dose (up to Day 20)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant who had signed the informed consent form (ICF) to participate in a study; it did not necessarily have to have a causal relationship with the treatment. An SAE was any untoward medical occurrence that at any dose met one or more of the following criteria: resulted in death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug.
Number of Participants With Clinically Significant Change From Baseline in Physical Examination	Baseline to Day 13	Physical examination included the following body systems: (1) respiratory system; (2) cardiovascular system; (3) nervous system (4) dermatologic system; and (5) gastrointestinal system. The clinically significant change assessment was based on investigator's judgment. Number of participants with clinically significant change from baseline in physical examination values were reported.
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters	Baseline to Day 13	The clinically significant change assessment was based on investigator's judgment. Number of participants with clinically significant change from baseline in laboratory values (hematology, serum chemistry, and urinalysis) were reported.
Number of Participants Based on Severity of TEAE	From start of study drug administration up to 7 days after the last dose (up to Day 20)	Severity of a TEAEs were determined by following criteria: Mild: event that did not generally interfere with usual activities of daily living; Moderate: event that interfere with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupt usual activities of daily living, significantly affects clinical status, or might require intensive therapeutic intervention.
Number of Participants Based on Causality of TEAEs	From start of study drug administration up to 7 days after the last dose (up to Day 20)	Causality of TEAEs to the study medication was assessed using the following categories: Related: An AE that followed a reasonable temporal sequence from administration of a drug (including the course after withdrawal of the drug), or for which a causal relationship was at least a reasonable possibility, that is, the relationship cannot be ruled out, although factors other than the drug, such as underlying diseases, complications, concomitant drugs and concurrent treatments, might also be responsible; Not Related: An AE that did not follow a reasonable temporal sequence from administration of a drug and/or that can reasonably be explained by other factors, such as underlying diseases, complications, concomitant medications and concurrent treatments.

Countries

United States

Participant flow

Recruitment details

Participants took part in the study at single investigative site in the United States from 25 May 2023 to 26 June 2023.

Pre-assignment details

Healthy participants were randomized in each of the 6 treatment sequences of this 3-period cross over study to receive a 50 milligram (mg) capsule of TAK-227 in the fasting state (Treatment A), fed predose state following a high-fat/high-calorie meal 30 minutes prior to dosing (Treatment B), or fed postdose state following a high-fat/high-calorie meal 30 minutes after dosing (Treatment C).

Participants by arm

Arm	Count
Treatment Sequence 1: (Treatment A + Treatment B + Treatment C) TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 1 under fasting condition as Treatment A, followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 2 administered with a high fat or high calorie meal 30 minutes prior to dosing as Treatment B, and further followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 3 administered with a high fat/high calorie meal 30 minutes after dosing as Treatment C. There was a washout period of not less than 4 days between each treatment period.	4
Sequence 2: (Treatment B + Treatment C + Treatment A) TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 1 administered with a high fat or high calorie meal 30 minutes prior to dosing as Treatment B, followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 2 administered with a high fat/high calorie meal 30 minutes after dosing as Treatment C, and further followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 3 under fasting condition as Treatment A . There was a washout period of not less than 4 days between each treatment period.	4
Treatment Sequence 3: (Treatment C + Treatment A + Treatment B) TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 1 administered with a high fat/high calorie meal 30 minutes after dosing as Treatment C, followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 2 under fasting condition as Treatment A, and further followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 3 administered with a high fat or high calorie meal 30 minutes prior to dosing as Treatment B. There was a washout period of not less than 4 days between each treatment period.	4
Treatment Sequence 4: (Treatment A + Treatment C + Treatment B) TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 1 under fasting condition as Treatment A, followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 2 administered with a high fat/high calorie meal 30 minutes after dosing as Treatment C, and further followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 3 administered with a high fat or high calorie meal 30 minutes prior to dosing as Treatment B. There was a washout period of not less than 4 days between each treatment period.	4
Treatment Sequence 5: (Treatment B + Treatment A + Treatment C) TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 1 administered with a high fat or high calorie meal 30 minutes prior to dosing as Treatment B, followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 2 under fasting condition as Treatment A, and further followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 3 administered with a high fat/high calorie meal 30 minutes after dosing as Treatment C. There will be a washout period of not less than 4 days between each treatment period.	4
Sequence 6: (Treatment C + Treatment B + Treatment A) TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 1 administered with a high fat/high calorie meal 30 minutes after dosing as Treatment C, followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 2 administered with a high fat or high calorie meal 30 minutes prior to dosing as Treatment B, and further followed by TAK-227 50 mg, capsule, single oral dose on Day 1 of Treatment Period 3 under fasting condition as Treatment A. There will be a washout period of not less than 4 days between each treatment period.	4
Total	24

Baseline characteristics

Characteristic	Treatment Sequence 4: (Treatment A + Treatment C + Treatment B)	Treatment Sequence 3: (Treatment C + Treatment A + Treatment B)	Sequence 2: (Treatment B + Treatment C + Treatment A)	Treatment Sequence 1: (Treatment A + Treatment B + Treatment C)	Total	Sequence 6: (Treatment C + Treatment B + Treatment A)	Treatment Sequence 5: (Treatment B + Treatment A + Treatment C)
Age, Continuous	42.8 years STANDARD_DEVIATION 8.1	39.5 years STANDARD_DEVIATION 4.2	43.0 years STANDARD_DEVIATION 10.23	49.0 years STANDARD_DEVIATION 6.38	42.3 years STANDARD_DEVIATION 8.19	36.5 years STANDARD_DEVIATION 10.47	43.0 years STANDARD_DEVIATION 7.7
Body Mass Index (BMI)	27.640 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.7334	27.795 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.6085	27.055 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.4694	28.613 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.1689	27.460 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.8896	26.280 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.0572	27.380 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.207
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	4 Participants	3 Participants	4 Participants	19 Participants	3 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants	0 Participants	1 Participants	0 Participants	5 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Height	171.3 centimeter (cm) STANDARD_DEVIATION 11.15	162.3 centimeter (cm) STANDARD_DEVIATION 12.71	165.0 centimeter (cm) STANDARD_DEVIATION 10.03	164.5 centimeter (cm) STANDARD_DEVIATION 8.43	167.8 centimeter (cm) STANDARD_DEVIATION 10.72	173.8 centimeter (cm) STANDARD_DEVIATION 6.65	169.8 centimeter (cm) STANDARD_DEVIATION 15.65
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	1 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	4 Participants	4 Participants	3 Participants	21 Participants	3 Participants	4 Participants
Region of Enrollment United States	4 Participants	4 Participants	4 Participants	4 Participants	24 Participants	4 Participants	4 Participants
Sex: Female, Male Female	1 Participants	2 Participants	3 Participants	2 Participants	11 Participants	1 Participants	2 Participants
Sex: Female, Male Male	3 Participants	2 Participants	1 Participants	2 Participants	13 Participants	3 Participants	2 Participants
Weight	80.78 kilogram (kg) STANDARD_DEVIATION 5.038	74.07 kilogram (kg) STANDARD_DEVIATION 18.007	74.18 kilogram (kg) STANDARD_DEVIATION 15.436	77.43 kilogram (kg) STANDARD_DEVIATION 7.135	77.63 kilogram (kg) STANDARD_DEVIATION 11.986	79.33 kilogram (kg) STANDARD_DEVIATION 4.64	80.00 kilogram (kg) STANDARD_DEVIATION 19.588

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 24	0 / 24	0 / 24
other Total, other adverse events	2 / 24	0 / 24	0 / 24
serious Total, serious adverse events	0 / 24	0 / 24	0 / 24

Outcome results

Primary

AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-227

Time frame: Day 1 pre-dose and at multiple time points (up to 36 hours) post-dose

Population: The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (for example, exposure to treatment, availability of measurements, and absence of major protocol violations) were included in the PK analyses. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: TAK-227 50 mg	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-227	1708 nanogramhour per milliliter(nghr/mL)	Geometric Coefficient of Variation 52
Treatment B: TAK-227 50 mg	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-227	983.7 nanogramhour per milliliter(nghr/mL)	Geometric Coefficient of Variation 50.8
Treatment C: TAK-227 50 mg	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-227	1070 nanogramhour per milliliter(nghr/mL)	Geometric Coefficient of Variation 51.8

Primary

AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-227

Time frame: Day 1 pre-dose and at multiple time points (up to 36 hours) post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: TAK-227 50 mg	AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-227	1582 nanogramhour per milliliter(nghr/mL)	Geometric Coefficient of Variation 65.9
Treatment B: TAK-227 50 mg	AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-227	969.2 nanogramhour per milliliter(nghr/mL)	Geometric Coefficient of Variation 51.2
Treatment C: TAK-227 50 mg	AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-227	1056 nanogramhour per milliliter(nghr/mL)	Geometric Coefficient of Variation 53

Primary

Cmax: Maximum Observed Plasma Concentration for TAK-227

Time frame: Day 1 pre-dose and at multiple time points (up to 36 hours) post-dose

Population: The pharmacokinetic (PK) set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (for example, exposure to treatment, availability of measurements, and absence of major protocol violations) were included in the PK analyses.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: TAK-227 50 mg	Cmax: Maximum Observed Plasma Concentration for TAK-227	464.4 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 89.8
Treatment B: TAK-227 50 mg	Cmax: Maximum Observed Plasma Concentration for TAK-227	190.9 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 50.6
Treatment C: TAK-227 50 mg	Cmax: Maximum Observed Plasma Concentration for TAK-227	370.0 nanogram per milliliter (ng/mL)	Geometric Coefficient of Variation 102.6

Secondary

Number of Participants Based on Causality of TEAEs

Causality of TEAEs to the study medication was assessed using the following categories: Related: An AE that followed a reasonable temporal sequence from administration of a drug (including the course after withdrawal of the drug), or for which a causal relationship was at least a reasonable possibility, that is, the relationship cannot be ruled out, although factors other than the drug, such as underlying diseases, complications, concomitant drugs and concurrent treatments, might also be responsible; Not Related: An AE that did not follow a reasonable temporal sequence from administration of a drug and/or that can reasonably be explained by other factors, such as underlying diseases, complications, concomitant medications and concurrent treatments.

Time frame: From start of study drug administration up to 7 days after the last dose (up to Day 20)