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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
128
TAK-951 placebo-matching SC injection
TAK-951 SC injection
California Clinical Trials Medical Group
Glendale, California, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: From the first dose of study drug up to follow-up or early termination (Up to approximately 32 days)
Part 1: Cmax: Maximum Observed Plasma Concentration for TAK-951
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose on Day 1 in Part 3
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