A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of TAK-123 After Intravenous Infusion in Japanese Healthy Adult Male Participants

A Single Center, Open-Label, Phase 1 Study to Evaluate the Pharmacokinetics, Safety and Tolerability of TAK-123 After Intravenous Infusion in Japanese Healthy Adult Male Subjects

The purpose of this study is to evaluate the PK, safety and tolerability of phenylacetate and benzoate after intravenous administration of TAK-123 in Japanese healthy adult male participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TAK-123

Detailed Description

The drug being tested in this study is called TAK-123. TAK-123 is being tested in Japanese healthy adult men. This study will look at the PK, safety and tolerability of phenylacetate and benzoates of people who administered TAK-123.

The study will enroll approximately 10 participants. All participants will be administered TAK-123 intravenously at the dose level of 3.75 g/m^2 of sodium phenylacetate and 3.75 g/m^2 of sodium benzoate.

- TAK-123 as 3.75 g/m^2 of sodium phenylacetate and 3.75 g/m^2 of sodium benzoate

This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately 8 days. Participants will make multiple visits to the clinic and be hospitalized for four days.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Toshima-ku, Tokyo, Japan
      • Sekino Clinical Pharmacology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. The participant is capable of understanding and complying with protocol requirements in the opinion of the investigator or sub-investigator.
2. The participant signs and dates a written informed consent form prior to the initiation of any study procedures.
3. The participant is a Japanese healthy adult male.
4. The participant is aged 20 to 45 years inclusive at the time of informed consent.
5. The participant weighs at least 50.0 kilogram (kg), and has a body mass index (BMI) between 18.5 and 25.0 kilogram per square meter (kg/m^2), inclusive, at Screening.
6. The participant is sterile, vasectomized or agrees to use an appropriate method of contraception throughout the treatment period.

Exclusion Criteria:

1. The participant has received any investigational drugs within 90 days before screening for this study (including the cases that at least 5 times the elimination half-lives of any investigational drugs have not yet passed).
2. The participant previously received TAK-123, its ingredients, or related compound before participation in this study except for the cases where benzoic acid is ingested as a food additive.
3. The participant is an employee of the study site, or immediate family member, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or who may be forced to provide consent.
4. The participants have previous or current history of diseases that may affect the participation in this study or study results, including uncontrolled, clinically relevant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, endocrine, hematologic, immune, skin disease or psychiatric disorder.
5. The participant has a history of multiple episodes or severe allergies (example, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerance to prescription drugs, over-the-counter (OTC) drugs or foods.
6. The participant has had an anaphylactic reaction to active ingredients or additives of TAK-123, ondansetron or additives of ondansetron, or salicylic acid associated with the intravenous administration of TAK-123.
7. The participant has a positive urine drug test at the time of screening.
8. The participant has a history of drug abuse (defined as any illicit drug use) or has a history of alcohol dependence within 2 years before the start of screening or is unwilling to agree to abstain from alcohol and drugs throughout the study.
9. The participant consumes 6 or more servings of caffeinated beverages (containing about 720 milligram [mg] of caffeine or more) such as coffee, tea, cola, or energy drinks per day.
10. The participant is a smoker who smoked cigarettes or used nicotine-containing products (such as nicotine patch) within 6 months before the study drug administration.
11. The participant has a history of cancer.
12. The participant has a positive test result for any of the following at the time of screening: hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, serological test for syphilis.
13. The participant has poor peripheral venous access.
14. The participant has undergone whole blood collection of at least 200 milliliter (mL) within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the start of the study drug administration.
15. The participant has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the start of the study drug administration.
16. The participant has undergone blood component collection within 2 weeks (14 days) prior to the start of the study drug administration.
17. The participant has any clinically relevant abnormality in vital signs or 12-lead electrocardiogram (ECG) at screening or predose of Day 1.
18. The participant has abnormal laboratory test values at screening indicating clinically relevant underlying disease, or showing alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 × upper limit of normal (ULN).
19. The participant has been on an abnormal diet (example, excessive drinking and eating or starvation condition) during the four weeks (28 days) prior to the start of the study drug administration in the opinion of the investigator or sub-investigator.
20. The participant who used or plans to use excluded concomitant medications, supplements, or dietary products during the predefined period in this study.
21. The participant is unlikely to comply with the protocol requirements or is unsuitable as a participant of this study for any other reason in the opinion of the investigator or sub-investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-123; TAK-123 as 3.75 gram per square meter (g/m^2) of sodium phenylacetate and 3.75 g/m^2 of sodium benzoate, intravenous administration over 90 minutes, followed by TAK-123 as 3.75 g/m^2 of sodium phenylacetate and 3.75 g/m^2 of sodium benzoate, intravenous administration over 24 hours.	Drug: TAK-123; TAK-123 infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax: Maximum Observed Plasma Concentration for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate)	Day 1: pre-infusion and 0.25, 0.75, 1.5, 2.5, 4.5, 6.5, 8.5, 10.5, 12.5, 16.5, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29.5, 30.5, 32.5 and 48 hours post-infusion
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate)	Day 1: pre-infusion and 0.25, 0.75, 1.5, 2.5, 4.5, 6.5, 8.5, 10.5, 12.5, 16.5, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29.5, 30.5, 32.5 and 48 hours post-infusion
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate)	Day 1: pre-infusion and 0.25, 0.75, 1.5, 2.5, 4.5, 6.5, 8.5, 10.5, 12.5, 16.5, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29.5, 30.5, 32.5 and 48 hours post-infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)	Day 1 up to Day 8

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): December 6, 2019
• Study Completion (Actual): December 6, 2019

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: TAK-123-1001; U1111-1237-4920 (Other Identifier: WHO); JapicCTI-195027 (Registry Identifier: JapicCTI)

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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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.: Yes