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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-227

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• 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

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 will be a washout period of at least 4 days between each dosing.	Drug: TAK-227; TAK-227 capsules.
Experimental: 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 will be a washout period of at least 4 days between each dosing.	Drug: TAK-227; TAK-227 capsules.
Experimental: 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 will be a washout period of at least 4 days between each dosing.	Drug: TAK-227; TAK-227 capsules.
Experimental: 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 will be a washout period of at least 4 days between each dosing.	Drug: TAK-227; TAK-227 capsules.
Experimental: 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 at least 4 days between each dosing.	Drug: TAK-227; TAK-227 capsules.
Experimental: 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 at least 4 days between each dosing.	Drug: TAK-227; TAK-227 capsules.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	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.	From start of study drug administration up to 7 days after the last dose (up to Day 20)
Number of Participants Based on Severity of TEAE	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.	From start of study drug administration up to 7 days after the last dose (up to Day 20)
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.	From start of study drug administration up to 7 days after the last dose (up to Day 20)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values	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.	Baseline to Day 13
Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiograms (ECG) Values	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.	Baseline to Day 13
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters	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.	Baseline to Day 13
Number of Participants With Clinically Significant Change From Baseline in Physical Examination	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.	Baseline to Day 13

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• To obtain more information about this study, click this link.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2023
• Primary Completion (Actual): June 19, 2023
• Study Completion (Actual): June 26, 2023

Study Registration Dates

• First Submitted: April 6, 2023
• First Submitted That Met QC Criteria: April 6, 2023
• First Posted (Actual): April 19, 2023

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-227-1001

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
• product manufactured in and exported from the U.S.: No