A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of TAK-954 in Healthy Adult Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and PK of single ascending intravenous doses of TAK-954.

Detailed Description
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The drug being tested in this study is called TAK-954. This study will assess the safety, tolerability, PK and PD of single ascending TAK-954 higher intravenous doses than those previously studied. The study will enroll approximately 6 participants. Participants will be randomly assigned (By chance, like flipping a coin) to one of the three treatment sequences-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). In each treatment sequence, each participant will receive 2 doses of active drug out of 3 dose levels (TAK-954 0.5 mg, TAK-954 1 mg, or TAK-954 2 mg) and 1 dose of Placebo. Dose escalation will be based on the available safety/tolerability data from the previous period. This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 73 days. Participants will make a final visit on Day 16 after receiving their last dose of study drug for a follow-up assessment.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, 3-Period, Incomplete Block Design Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-954 in Healthy Adult Participants

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: TAK-954
* Drug: TAK-954 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) greater than or equal to (>=) 18 and less than or equal to (<=) 32 kilogram per square meter (kg/m^2), weighing >=50 kilogram (kg) at screening. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, orthostatic vital signs, or ECGs, as deemed by the Investigator or designee. Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose and throughout the study, based on participant self-reporting. Exclusion Criteria: History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing. Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing. Recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks of first dosing.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Period 1: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. Period 2: TAK-954 0.1 milligram (mg), infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 1 mg infusion, administered intravenously over 60-minutes, once on Day 2. Period 3: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 2 mg infusion, administered intravenously over 60-minutes, once on Day 2. A washout period of at least 16 days will be maintained between each Treatment Period. | Drug: TAK-954<br>* TAK-954 infusion administered intravenously.<br>Drug: TAK-954 Placebo<br>* TAK-954 placebo-matching infusion intravenous.<br>|
| Experimental: Sequence 2<br>Period 1: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 0.5 mg infusion, administered intravenously over 60-minutes once on Day 2. Period 2: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. Period 3: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 2 mg, infusion, administered intravenously over 60-minutes, once on Day 2. A washout period of at least 16 days will be maintained between each Treatment Period. | Drug: TAK-954<br>* TAK-954 infusion administered intravenously.<br>Drug: TAK-954 Placebo<br>* TAK-954 placebo-matching infusion intravenous.<br>|
| Experimental: Sequence 3<br>Period 1: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 0.5 mg, infusion, administered intravenously over 60-minutes once on Day 2. Period 2: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 1 mg, infusion, administered intravenously over 60-minutes, once on Day 2. Period 3: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. A washout period of at least 16 days will be maintained between each Treatment Period. | Drug: TAK-954<br>* TAK-954 infusion administered intravenously.<br>Drug: TAK-954 Placebo<br>* TAK-954 placebo-matching infusion intravenous.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954 |  | Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52) | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954 |  | Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52) | 
| Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954 |  | Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52) | 
| Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954 |  | Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52) | 
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 |  | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose | 
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 |  | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose | 
| Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954 |  | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose | 
| CL: Total Clearance After Intravenous Administration for TAK-954 |  | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose | 
| Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 |  | Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose | 
| Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose |  | Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose | 
| Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose |  | Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose |  | Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose | 
| Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose |  | Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose | 
| Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose |  | Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose | 
| Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose |  | Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose | 
| CLR: Renal Clearance for TAK-954 |  | Day 2 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 With First Stool of TAK-954 Within 36 Hours Post-dose on Day 2 |  | Day 2 dosing and at multiple time points (up to 36 hours) post-dose | 
| Mean Number of Stools of TAK-954 Within 36 Hours Post-dose on Day 2 |  | Day 2 dosing and at multiple time points (up to 36 hours) post-dose | 
| Instances of Stool Type of TAK-954 Based on Bristol Stool Form Scale | Number of occurrences for each stool type was reported based on their type assessed from Bristol Stool form scale. The Bristol Stool Form Scale was used to assess the stool shape using a 7-point scale. Where, Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. A score of 1 or 2 indicates constipation and a score of 6 or 7 indicates diarrhea. | Day 2 dosing and at multiple time points (up to 36 hours) post-dose | 

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