A Study of TAK-951 in Healthy Adults

Study Overview
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Brief Summary
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This is a study of TAK-951 for people with symptoms of nausea and vomiting. The main aims of this study in healthy adults are as follows: To check for side effects from TAK-951 when given at a slow and fast infusion rate. To learn how much TAK-951 participants can receive without getting side effects from it. To check how much TAK-951 stays in the blood over time to work out the best dose. Participants will receive a single infusion of either TAK-951 or placebo. In this study, a placebo looks like TAK-951 but does not have any medicine in it. Participants will receive either a low dose or high dose of TAK-951. The infusion will take from 1-3 hours. Participants will stay in the study clinic for about 4 days to receive the study medicine (TAK-951 or placebo) and check for side effects. They will have follow-up visits at the clinic about 2 weeks and 4 weeks after treatment.

Detailed Description
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The drug being tested in this study is called TAK-951. The study evaluated the safety, tolerability and pharmacokinetics (PK) of TAK-951 in healthy participants. The study enrolled 128 healthy participants and consisted of 2 parts: Single-rising Dose (SRD) part (13 cohorts) of sequential panel design, and Multiple-rising Dose (MRD) part (5 cohorts) of sequential panel design. Participants in each cohort were randomized to receive treatment with TAK-951 or matching placebo using SC injection, once daily on Day 1 (for SRD part) and twice daily (BID) on Days 1 through 5 (for MRD part) following a minimum fast of 8 hours. This single center trial was conducted in the United States. The overall time to participate in this study was approximately 155 days.

Official Title
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A Randomized, Double-blind, Placebo-Controlled, Three-part Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-951 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: TAK-951 Placebo
* Drug: TAK-951


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Have a body mass index (BMI) ≥18 and ≤30.0 (kg/m^2) at the Screening Visit. Exclusion Criteria: The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency antibody/antigen, at the Screening Visit. Note: Participants with positive hepatitis B virus or hepatitis C virus serology may be enrolled if quantitative polymerase chain reaction for hepatitis B virus or hepatitis C virus ribonucleic acid is negative. The participant had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks before the Screening Visit. Heavy consumption of alcohol within 3 months before screening (>7 drinks/week for women, >14 drinks/week for men, where 1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) or use of soft drugs (such as marijuana) within 3 months before screening, or hard drugs (such as cocaine and phencyclidine) within 1 year before Screening. The participant has used nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 28 days before check-in (Day -1) or cotinine test is positive at Screening or Day -1. The participant has had 3 incidences of vasovagal syncope within the last 5 years. The participant has Brugada syndrome (right bundle branch block [RBBB] pattern with ST-elevation in leads V1-V3). The participant has an average semirecumbent systolic blood pressure <90 millimeters of mercury (mm Hg) or diastolic blood pressure <60 mm Hg at Screening or admission. The participant has an average heart rate (HR) <60 or >100 beats per minute (bpm) [at Screening, at Day -1, or at predose]; athletic participants with an average HR <60 bpm can be enrolled only with medical monitor approval. The participant has orthostatic hypotension defined as a decrease in systolic blood pressure ≥20 mm Hg or a decrease in diastolic blood pressure ≥10 mm Hg after 2 minutes of standing when compared with blood pressure from the sitting position at Screening, and at Day -1. Participants with postural orthostatic tachycardia, defined as HR >120 bpm standing, will also be excluded.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Part 1 (SRD): Pooled Placebo<br>TAK-951 placebo-matching, single dose, subcutaneous (SC) injection, on Day 1 in fasted healthy participants in the single-rising dose (SRD) period. | Drug: TAK-951 Placebo<br>* TAK-951 placebo-matching SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 2: TAK-951 Dose 1<br>TAK-951 Dose 1, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 1: TAK-951 Dose 2<br>TAK-951 Dose 2, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 15: TAK-951 Dose 2<br>TAK-951 Dose 2, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 3: TAK-951 Dose 3<br>TAK-951 Dose 3, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 4: TAK-951 Dose 4<br>TAK-951 Dose 4, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 5: TAK-951 Dose 5<br>TAK-951 Dose 5, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 6: TAK-951 Dose 6<br>TAK-951 Dose 6, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 13: TAK-951 Dose 7<br>TAK-951 Dose 7, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 14: TAK-951 Dose 8<br>TAK-951 Dose 8, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 16: TAK-951 Dose 9<br>TAK-951 Dose 9, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 17: TAK-951 Dose 10<br>TAK-951 Dose 10, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 1 (SRD): Cohort 18: TAK-951 Dose 11<br>TAK-951 Dose 11, single dose, SC injection, on Day 1 in fasted healthy participants in the SRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Placebo Comparator: Part 3 (MRD): Pooled Placebo<br>TAK-951 placebo-matching, SC injection, for 5 days from Days 1 to 5 in fasted healthy participants in the multiple-rising dose (MRD) period. | Drug: TAK-951 Placebo<br>* TAK-951 placebo-matching SC injection<br>|
| Experimental: Part 3 (MRD): Cohort 10: TAK-951 Dose 1A<br>TAK-951 Dose 1A, SC injection, for 5 days from Days 1 to 5 in fasted healthy participants in the MRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 3 (MRD): Cohort 11: TAK-951 Dose 2A<br>TAK-951 Dose 2A, SC injection, for 5 days from Days 1 to 5 in fasted healthy participants in the MRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 3 (MRD): Cohort 12: TAK-951 Dose 3A<br>TAK-951 Dose 3A, SC injection, for 5 days from Days 1 to 5 in fasted healthy participants in the MRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|
| Experimental: Part 3 (MRD): Cohort 20: TAK-951 Dose 4A<br>TAK-951 Dose 4A, SC injection, for 5 days from Days 1 to 5 in fasted healthy participants in the MRD period. | Drug: TAK-951<br>* TAK-951 SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1 and 3: Percentage of Participants With Clinically Significant Physical Examination Findings | Physical examination included the examination of the abdomen; extremities; head, eyes, ears, nose (HEENT); neurological; skin and mucosae; thorax. | From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days) | 
| Parts 1 and 3: Percentage of Participants With Markedly Abnormal Values of Vital Signs Parameters | The criteria for markedly abnormal values of vital signs' parameters were: Pulse Rate (beats/minute) <50 and >120; Systolic Blood Pressure [millimeters of mercury (mmHg)] <85 and >180; Diastolic Blood Pressure (mmHg) <50 and >110; Temperature [degrees Celsius (C)] <35.6 and >37.7. Only categories with atleast one participant with events are reported. | From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days) | 
| Parts 1 and 3: Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters | The criteria for markedly abnormal values of 12-lead ECG parameters were: ECG Mean Heart Rate (beats/min) <50 beats per minute and >120 beats per minute; PR Interval, Aggregate [milliseconds (msec)] <=80 msec and >=200 msec; QRS Duration, Aggregate (msec) <=80 msec and >=120 msec; QT Interval with Fridericia Correction Method (QTcF) Interval, Aggregate (msec) >=500 msec or >=30 msec change from Baseline and >=450 msec. Only categories with atleast one participant with event are reported. | From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days) | 
| Parts 1 and 3: Percentage of Participants With Markedly Abnormal Values of Laboratory Parameters | The laboratory parameters of chemistry, and hematology were assessed. Clinical laboratory tests included serum chemistry, hematology, and urinalysis. MAV criteria: Alanine aminotransferase(U/L) >3xupper limit of normal(ULN); Albumin<2.5g/dL,<25g/L; Alkaline phosphatase (U/L)>3 x ULN; Aspartate aminotransferase (U/L)>3 x ULN; Bilirubin>1.5mg/dL, >34.2 µmol/L; Calcium<8.0 mg/dL,LLN-<2.0mmol/L, >1.0mmol/L; Carbon dioxide <8.0 (mmol/L); Chloride<75 mmol/L,>126 mmol/L; Creatinine>177µmol/L; Gamma glutamyl transferase (U/L)>2.0 mg/dL, >3.0 x ULN; Glucose<3 mmol/L,>10 mmol/L; Potassium<3.0 mmol/L >5.5 mmol/L; Protein(g/L)<0.8 x LLN >1.2 x ULN; Sodium<130mmol/L >150mmol/L; Urea nitrogen >10.7; Erythrocytes 10^12erythrocytes/L) <0.8 x LLN,>1.2 x ULN; Hematocrit(%) <0.8 x LLN,>1.2xULN; Hemoglobin(g/L)<0.8 x LLN, >1.2 x ULN; Leukocytes(10^9 leukocytes/L)<0.5 x LLN >1.5 x ULN; platelets(10^9 platelets/L)<75->600. Only categories with atleast one participant with event are reported. | From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days) | 
| Parts 1 and 3: Percentage of Participants With Treatment-Emergent Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. | From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days) | 
| Parts 1 and 3: Percentage of Participants With Positive Immunogenicity (ADA) Status |  | From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-951 |  | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Part 1 | 
| Part 1: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-951 |  | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Part 1 | 
| Part 3: Cmax: Maximum Observed Plasma Concentration for TAK-951 on Day 1 |  | Pre-dose and at multiple time points (up to 24 hours) post-dose on Day 1 in Part 3 | 
| Part 3: AUCτ: Area Under the Plasma Concentration-time Curve During a Dosing Interval Tau (τ), From Time of First Daily Dose to 8 Hours for TAK-951 on Day 1 |  | Pre-dose and at multiple time points (up to 24 hours) post-dose on Day 1 in Part 3 | 

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