Clinical trial NCT04155567: A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of TAK-123 After Intravenous Infusion in Japanese Healthy Adult Male Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-11-07
Enrollment: 10
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate)
timeFrame: 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 outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Day 8
Other outcomes:
Locations:
city: Toshima-ku
country: Japan
facility: Sekino Clinical Pharmacology Clinic
state: Tokyo
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: