Healthy Volunteers
Conditions
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.
Interventions
DRUGTAK-123
TAK-123 infusion
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Day 1 up to Day 8 |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in Japan from 13 November 2019 to 06 December 2019.
Pre-assignment details
Healthy Japanese male participants were enrolled in the study to receive TAK-123 3.75 gram per square meter (g/m\^2) sodium phenylacetate (NaPA) and 3.75 g/m\^2 sodium benzoate (NaBZ), as loading dose followed by an equivalent maintenance dose.
Participants by arm
| Arm | Count |
|---|---|
| TAK-123 3.75 g/m^2 NaPA and NaBZ TAK-123 3.75 g/m\^2 NaPA and TAK-123 3.75 g/m\^2 NaBZ as loading dose, infusion, intravenously over 90 minutes, followed by TAK-123 3.75 g/m\^2 NaPA and TAK-123 3.75 g/m\^2 NaBZ maintenance dose, infusion, intravenously over 24 hours on Day 1. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | TAK-123 3.75 g/m^2 NaPA and NaBZ | — |
|---|---|---|
| Age, Continuous | 33.1 years STANDARD_DEVIATION 5.09 | — |
| Alcohol Classification Drank A Few Times Per Month | 5 Participants | — |
| Alcohol Classification Never Drank | 5 Participants | — |
| Body Mass Index (BMI) | 21.74 kilogram per square meter (kg/m˄2) STANDARD_DEVIATION 1.532 | — |
| Caffeine Classification Had Caffeine Consumption | 1 Participants | — |
| Caffeine Classification Had No Caffeine Consumption | 9 Participants | — |
| Height | 173.7 centimeter (cm) STANDARD_DEVIATION 5.03 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Japan | 10 Participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 10 Participants | — |
| Smoking Classification Former Smoker | 2 Participants | — |
| Smoking Classification Never Smoked | 8 Participants | — |
| Weight | 65.68 kilogram (kg) STANDARD_DEVIATION 6.994 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 6 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate)
Time frame: 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
Population: The PK analysis set was defined as all participants who received at least one dose of TAK-123 and provided sufficient PK measurements available to estimate at least one estimable PK parameter. Here number analyzed n are the participants who were evaluable for the outcome measure at given categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-123 3.75 g/m^2 NaPA and NaBZ | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate) | Phenylacetate | 3932 h*mcg/mL | Geometric Coefficient of Variation 22.6 |
| TAK-123 3.75 g/m^2 NaPA and NaBZ | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate) | Phenylacetylglutamine | 1140 h*mcg/mL | Geometric Coefficient of Variation 16.4 |
| TAK-123 3.75 g/m^2 NaPA and NaBZ | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate) | Hippurate | 427.3 h*mcg/mL | Geometric Coefficient of Variation 21.2 |
Primary
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)
Time frame: 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
Population: The PK analysis set was defined as all participants who received at least one dose of TAK-123 and provided sufficient PK measurements available to estimate at least one estimable PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-123 3.75 g/m^2 NaPA and NaBZ | 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) | Phenylacetate | 3931 hour*microgram per milliliter (h*mcg/mL) | Geometric Coefficient of Variation 22.6 |
| TAK-123 3.75 g/m^2 NaPA and NaBZ | 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) | Benzoate | 752.6 hour*microgram per milliliter (h*mcg/mL) | Geometric Coefficient of Variation 16.7 |
| TAK-123 3.75 g/m^2 NaPA and NaBZ | 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) | Phenylacetylglutamine | 1135 hour*microgram per milliliter (h*mcg/mL) | Geometric Coefficient of Variation 16.2 |
| TAK-123 3.75 g/m^2 NaPA and NaBZ | 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) | Hippurate | 413.5 hour*microgram per milliliter (h*mcg/mL) | Geometric Coefficient of Variation 22.2 |
Primary
Cmax: Maximum Observed Plasma Concentration for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate)
Time frame: 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
Population: The pharmacokinetics (PK) analysis set was defined as all participants who received at least one dose of TAK-123 and provided sufficient PK measurements available to estimate at least one estimable PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-123 3.75 g/m^2 NaPA and NaBZ | Cmax: Maximum Observed Plasma Concentration for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate) | Phenylacetate | 300.7 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 5.2 |
| TAK-123 3.75 g/m^2 NaPA and NaBZ | Cmax: Maximum Observed Plasma Concentration for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate) | Benzoate | 233.2 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 6.9 |
| TAK-123 3.75 g/m^2 NaPA and NaBZ | Cmax: Maximum Observed Plasma Concentration for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate) | Phenylacetylglutamine | 69.77 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 19.8 |
| TAK-123 3.75 g/m^2 NaPA and NaBZ | Cmax: Maximum Observed Plasma Concentration for Phenylacetate, Benzoate, and Their Metabolites (Phenylacetylglutamine and Hippurate) | Hippurate | 54.13 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 18 |
Secondary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 up to Day 8
Population: The safety analysis set was defined as all participants who received at least one dose of TAK-123.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-123 3.75 g/m^2 NaPA and NaBZ | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 6 Participants |