A Study of TAK-510 in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
This is a study of TAK-510 for people with symptoms of feeling sick (nausea) or being sick (vomiting). The main aims of the study are to check if healthy adults have side effects from TAK-510 and to check how much TAK-510 they can receive without getting side effects from it. The study will be in 3 parts. Participants will take part in only 1 of the 3 parts of the study. At the first visit, the study doctor will check if each person can take part. For those who can take part, they will be placed in 1 of many small groups. The 1st groups will join Part 1 of the study, the 2nd groups will join Part 2 and the 3rd groups will join Part 3. They will receive an injection under the skin of either TAK-510 or placebo. In this study, a placebo will look like the TAK-510 injection but will not have any medicine in it. In Part 1, the 1st group of participants will receive 1 injection of either TAK-510 or placebo. Different participants within this group will receive lower to higher doses of TAK-510. The participants in this group will stay in the clinic for 4 days after their injection for some tests and check for any side effects from their treatment. In Part 2, the 2nd group of participants will receive an injection of either TAK-510 or placebo, once a day for 5 days. Different participants within this group will receive lower to higher doses of TAK-510. The participants in this group will stay in the clinic for 9 days after their 1st injection for some tests and check for any side effects from their treatment. In Part 3, the 3rd group of participants will visit the clinic 2 times. At the 1st visit, they will receive an injection either of TAK-510 or placebo, once a day for 7 days. Each participant in this group will receive lower to higher doses of TAK-510. They will stay in the clinic for 8 days after their 1st injection for some tests and check for any side effects from their treatment. At the 2nd clinic visit, each participant will receive 1 single injection of TAK-510 or placebo. This will happen 7 days after their last injection from the previous clinic visit. They will receive the same dose as their previous dose. They will stay in the clinic for 3 days for some tests and check for any side effects from their treatment. After treatment, all participants in the study will return to the clinic for a weekly check-up visit for up to 3 weeks.

Detailed Description
-----------------
The drug being tested in this study is called TAK-510. The study will look at the safety, tolerability, and PK of TAK-510 in healthy participants. The study will enroll up to approximately 224 healthy participants. Participants in each cohort will be randomized to receive treatment with TAK-510 or matching placebo which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). The study consists of 3 parts and up to 28 cohorts as mentioned below. TAK-510, Part 1: Single rising dose (SRD) design to assess the safety, immunogenicity, tolerability, and PK of TAK-510 TAK-510, Part 2: Multiple rising dose (MRD) design to assess the safety, immunogenicity, tolerability, and PK of TAK-510 TAK-510, Part 3: Dose titration and redosing design to assess the safety, immunogenicity, tolerability, and PK of TAK-510 This multi-center trial will be conducted in the United States. The overall duration of the study is approximately 57 days. Participants will be followed up for 7 days after the last dose of study drug for a follow-up assessment.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-510 in Healthy Subjects

Conditions
-----------------
Healthy Participants

Intervention / Treatment
-----------------
* Drug: TAK-510
* Drug: TAK-510 Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Continuous nonsmoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to dosing and throughout the study. Body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 30.0 kilogram per square meter (kg/m^2) at the screening visit. Exclusion Criteria: Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency antibody/antigen, at the screening visit. Had major surgery or donated or lost 1 unit of blood (approximately 500 milliliter [mL]) within 4 weeks before the screening visit. Unable to refrain from or anticipates using all medications including herbal medicines beginning approximately 7 days before administration of the first dose of study drug, throughout the study until 2 days after discharge. Unable to refrain from or anticipates using marijuana or cannabis-containing products beginning approximately 7 days before administration of the first dose of study drug, throughout the study until after the last PK dose. Has had a previous major psychotic disorder. Has an average semirecumbent blood pressure (BP) less than 90/60 millimeter of mercury (mmHg) or greater than 140/90 mmHg from screening to predose, inclusive. Any assessments on Day -1, where 2 consecutive time point values do not meet this criterion must be discussed with the medical monitor for approval. Has orthostatic hypotension defined as a decrease in systolic BP >=20 mmHg or a decrease in diastolic BP >=10 mmHg at approximately 3 minutes of standing when compared with BP from the semirecumbent position, at screening to predose assessments, inclusive. In asymptomatic participants, any assessments after screening that do not meet this criterion may be repeated after the participant has remained in the semirecumbent or supine position for 15 minutes. If the repeat assessment is exclusionary based on the above criterion, the participant will not be eligible. If the repeat assessment is not exclusionary, the participant will be eligible. Has postural orthostatic tachycardia, defined as an increase of greater than (>) 30 beats per minute (bpm) or heart rate (HR) >120 bpm at approximately 3 minutes, of standing, at screening to predose assessments, inclusive. Any assessments after screening that do not meet this criterion may be repeated with the participant remaining standing for up to a total of 5 minutes, provided that the participant remains asymptomatic. If the repeat assessment occurring within 5 minutes is exclusionary based on the above criterion, the participant will not be eligible. A confirmed orthostatic increase of >30 bpm, but less than (<) 40 bpm, on 1 or more Day -1 assessments may not be considered exclusionary if not considered clinically significant by the investigator and the medical monitor. Such assessments must be discussed with the medical monitor prior to determination that the participant is eligible to proceed. Has a known or suspected current coronavirus disease 2019 (COVID-19) infection or is at risk of COVID-19 infection as assessed by the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-510: Part 1<br>TAK-510 at starting dose of 5 microgram (mcg) or placebo-matching solution, subcutaneously, once on Day 1. Staggered dosing will be done in the first cohort of Part A (Cohort 1). Staggered dosing in subsequent Cohorts (Cohorts 2-12 and 21-25) will be used based on emerging safety, tolerability, and PK data from Cohort 1 as determined in the dose escalation meeting. | Drug: TAK-510<br>* TAK-510 solution.<br>Drug: TAK-510 Placebo<br>* TAK-510 placebo-matching solution.<br>|
| Experimental: TAK-510: Part 2<br>TAK-510 to be decided (TBD) or placebo-matching solution, subcutaneously, once daily from Day 1 through Day 5. Dose of MRD Cohorts (Cohorts 13-17 and 26-28) of Part 2 will be determined based on emerging safety, tolerability, and available PK data from Part 1 (SRD) and any available PK data from Part 2 as determined in the dose escalation meeting. | Drug: TAK-510<br>* TAK-510 solution.<br>Drug: TAK-510 Placebo<br>* TAK-510 placebo-matching solution.<br>|
| Experimental: TAK-510: Part 3<br>TAK-510 TBD or placebo-matching solution, subcutaneously, once daily from Days 1 to 7. Dose of dose titration and redosing Cohorts (Cohorts 18-20) of Part 3 will be based on emerging safety, tolerability, and available PK data from Part 1 (SRD) and Part 2 (MRD) as determined in the dose escalation meeting. Single redosing will be performed on Day 14 after 7 days of washout period following the 7 days treatment period. | Drug: TAK-510<br>* TAK-510 solution.<br>Drug: TAK-510 Placebo<br>* TAK-510 placebo-matching solution.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose |  | Baseline up to Day 29 | 
| Number of Participants who Meet the Markedly Abnormal Criteria for Electrocardiogram (ECG) Parameters at Least Once Post Dose |  | Baseline up to Day 29 | 
| Number of Participants who Meet the Markedly Abnormal Criteria for Laboratory Value at Least Once Post Dose |  | Baseline up to Day 29 | 
| Number of Participants Reporting One or More Treatment-emergent Adverse Event (TEAE) |  | Baseline up to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1 and 2, Cmax: Maximum Observed Plasma Concentration for TAK-510 |  | Day 1 (Part 1) pre-dose and at multiple time points (up to 96 hours) post-dose; Day 1 (Part 2): pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Parts 1 and 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-510 |  | Day 1 (Part 1) pre-dose and at multiple time points (up to 96 hours) post-dose; Day 1 (Part 2): pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 1, CL/F: Apparent Clearance After Extravascular Administration for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 1, Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to tau Over Dosing Interval for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Part 2, AUCτss: Area Under the Plasma Concentration-time Curve From Time 0 to tau Over Dosing Interval at Steady State for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, Cmaxss: Maximum Observed Plasma Concentration at Steady State for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, Tmaxss: Time to Reach the Maximum Observed Plasma Concentration at Steady State for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, T1/2z: Terminal Disposition Phase Half-life at Steady State for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, CL/F: Apparent Clearance After Extravascular Administration at Steady State for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, Vz/F: Apparent Volume of Distribution During the Terminal Disposition Phase After Extravascular Administration at Steady State for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, Ctrough: Observed Plasma Concentration at the end of a Dosing Interval at Steady State for TAK-510 |  | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, Rac (AUC): Accumulation Ratio Based on AUCτ at Steady State for TAK-510 | The accumulation ratio based on AUCτ at steady state for TAK-510 will be calculated as AUCτ at steady state/AUCτ after a single dose. | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Part 2, Rac (Cmax): Accumulation Ratio Based on Cmax at Steady State for TAK-510 | The accumulation ratio based on Cmax at steady state for TAK-510 will be calculated as Cmax at steady state/Cmax after a single dose. | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Day 5 pre-dose and at multiple time points (up to 96 hours) post-dose | 
| Parts 1 and 2, Aet: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-510 |  | Day 1 (Parts 1 and 2) and Day 5 (Part 2) pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Parts 1 and 2, Aet1-t2: Amount of Drug Excreted in Urine From Time 1 to Time 2 for TAK-510 |  | Day 1 (Parts 1 and 2) and Day 5 (Part 2) pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Parts 1 and 2, Aeτ: Amount of Drug Excreted in Urine During a Dosing Interval (tau) at Steady State for TAK-510 |  | Day 1 (Parts 1 and 2) and Day 5 (Part 2) pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Parts 1 and 2, fe,t: Fraction of Administered Dose of Drug Excreted From Urine From Time 0 to Time t for TAK-510 |  | Day 1 (Parts 1 and 2) and Day 5 (Part 2) pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Parts 1 and 2, CLR: Renal clearance for TAK-510 |  | Day 1 (Parts 1 and 2) and Day 5 (Part 2) pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Part 3, Number of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Single Subcutaneous Rechallenge Doses After a Washout From Multiple Subcutaneous Dose Regimens |  | Baseline up to Day 29 | 
| Part 3, Number of Participants who Meet the Markedly Abnormal Criteria for ECG Parameters at Least Once Post Single Subcutaneous Rechallenge Doses After a Washout From Multiple Subcutaneous Dose Regimens |  | Baseline up to Day 15 | 
| Part 3, Number of Participants who Meet the Markedly Abnormal Criteria for Laboratory Value at Least Once Post Single Subcutaneous Rechallenge Doses After a Washout From Multiple Subcutaneous Dose Regimens |  | Baseline up to Day 29 | 
| Part 3, Number of Participants Reporting One or More TEAE Post Single Subcutaneous Rechallenge Doses After a Washout From Multiple Subcutaneous Dose Regimens |  | Baseline up to Day 29 | 
| Number of Participants Based on Antidrug Antibody (ADA) Levels in Serum | The number participants in each category of the immunogenicity status (ADA-negative or ADA-positive) will be determined in this study. A 3-tiered ADA testing strategy will be used in this study. A Sample will initially be screened for ADA by the ADA screening assay. Any positive sample in the screening assay is considered a potential positive, which will be confirmed for true positivity by the confirmatory assay. If a sample is confirmed as an ADA true positive, ADA titer will be assessed. | Baseline up to Day 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Therapy