Trial Outcomes & Findings for A Study of TAK-951 to Stop Adults Getting Nausea and Vomiting After Planned Surgery (NCT NCT04557189)

Results Overview

Percentage of participants with complete response, defined as no emesis (vomiting or retching) and no need for rescue therapy (indicated if vomiting/retching and/or nausea score ≥4 or upon participant's request) were reported. The severity of nausea was scored using a self-reported, 11-point numerical Verbal Rating Scale (VRS), where 0 represents no nausea and 10 represents the worst nausea possible. Significant nausea was defined as a VRS score ≥4. Percentages are rounded off to whole number at the nearest single decimal.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

89 participants

Primary outcome timeframe

6 hours post-surgery (Day 1)

Results posted on

2023-04-21

Participant Flow

Participants took part in the study at 7 sites in the United States from 20 October 2020 to 21 March 2022. Participants with a diagnosis of postoperative nausea and vomiting (PONV) were enrolled in 1:1 ratio.

Participants received prophylaxis either with ondansetron before induction followed by TAK-951 placebo or prophylaxis with ondansetron placebo before induction followed by TAK-951 4 mg. Due to dosing error, of the 39 participants in the TAK-951 4 mg SC group, 18 participants received an unintended mis-dose of TAK-951 redacted mg. Data for these participants were collected and reported separately only for the outcome measures reporting data for the safety, pharmacokinetic, and immunogenicity set.

Participant milestones

Participant milestones
Measure	Ondansetron 4 mg IV Participants received prophylaxis with ondansetron 4 mg, intravenously (IV) immediately before induction and TAK-951 placebo subcutaneously (SC) approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Overall Study STARTED	44	45
Overall Study Full Analysis Set (FAS)	41	39
Overall Study Pharmacokinetic (PK) Set	0	21
Overall Study Immunogenicity Set	0	21
Overall Study Unintended Mis-dose Due to Dosing Error	0	18
Overall Study COMPLETED	38	36
Overall Study NOT COMPLETED	6	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Ondansetron 4 mg IV Participants received prophylaxis with ondansetron 4 mg, intravenously (IV) immediately before induction and TAK-951 placebo subcutaneously (SC) approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Overall Study Adverse Event	0	1
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	2	1
Overall Study Reason not Specified	3	6

Baseline Characteristics

A Study of TAK-951 to Stop Adults Getting Nausea and Vomiting After Planned Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	Total n=80 Participants Total of all reporting groups
Age, Continuous	46.0 years STANDARD_DEVIATION 10.32 • n=5 Participants	45.1 years STANDARD_DEVIATION 10.57 • n=7 Participants	45.6 years STANDARD_DEVIATION 10.39 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	38 Participants n=7 Participants	76 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	29 Participants n=7 Participants	62 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	27 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	41 Participants n=5 Participants	39 Participants n=7 Participants	80 Participants n=5 Participants
Weight	93.85 kg STANDARD_DEVIATION 27.439 • n=5 Participants	87.61 kg STANDARD_DEVIATION 22.258 • n=7 Participants	90.81 kg STANDARD_DEVIATION 25.087 • n=5 Participants
Height	164.57 cm STANDARD_DEVIATION 8.448 • n=5 Participants	164.32 cm STANDARD_DEVIATION 9.499 • n=7 Participants	164.44 cm STANDARD_DEVIATION 8.919 • n=5 Participants
Body Mass Index (BMI)	34.41 kg/m^2 STANDARD_DEVIATION 8.909 • n=5 Participants	32.47 kg/m^2 STANDARD_DEVIATION 7.574 • n=7 Participants	33.47 kg/m^2 STANDARD_DEVIATION 8.290 • n=5 Participants

PRIMARY outcome

Timeframe: 6 hours post-surgery (Day 1)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery.

Percentage of participants with complete response, defined as no emesis (vomiting or retching) and no need for rescue therapy (indicated if vomiting/retching and/or nausea score ≥4 or upon participant's request) were reported. The severity of nausea was scored using a self-reported, 11-point numerical Verbal Rating Scale (VRS), where 0 represents no nausea and 10 represents the worst nausea possible. Significant nausea was defined as a VRS score ≥4. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Complete Response in the Immediate Postoperative Period	48.8 percentage of participants Interval 0.335 to 0.641	71.8 percentage of participants Interval 0.577 to 0.859	—

SECONDARY outcome

Timeframe: Within 24 hours post-surgery (up to Day 2)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery.

Percentage of participants with complete response, defined as no emesis (vomiting or retching) and no need for rescue therapy (indicated if vomiting/retching and/or nausea score ≥4 or upon participant's request) were reported. The severity of nausea was scored using a self-reported, 11-point numerical Verbal Rating Scale (VRS), where 0 represents no nausea and 10 represents the worst nausea possible. Significant nausea was defined as a VRS score ≥4. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Complete Response Within 24 Hours Post-Surgery	41.5 percentage of participants Interval 0.264 to 0.565	59.0 percentage of participants Interval 0.435 to 0.744	—

SECONDARY outcome

Timeframe: Within 6 hours post-surgery (Day 1)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery.

Percentage of participants with emesis, defined as vomiting (the forceful discharge of even the smallest amount of stomach contents) or retching (the same muscular movements as vomiting but without expulsion of stomach contents) were reported. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Emesis in the First 6 Hours Post-Surgery	17.1 percentage of participants Interval 0.056 to 0.286	7.7 percentage of participants Interval 0.016 to 0.209	—

SECONDARY outcome

Timeframe: Within 24 hours post-surgery (up to Day 2)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery.

Percentage of participants with emesis, defined as vomiting (the forceful discharge of even the smallest amount of stomach contents) or retching (the same muscular movements as vomiting but without expulsion of stomach contents) were reported. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Emesis Within 24 Hours Post-Surgery	24.4 percentage of participants Interval 0.112 to 0.375	10.3 percentage of participants Interval 0.029 to 0.242	—

SECONDARY outcome

Timeframe: Within 6 hours post-surgery (Day 1)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery.

Percentage of participants without nausea, defined as urge to vomit without the presence of expulsive muscular movements were reported. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Absence of Nausea in the First 6 Hours Post-Surgery	41.5 percentage of participants Interval 0.264 to 0.565	59.0 percentage of participants Interval 0.435 to 0.744	—

SECONDARY outcome

Timeframe: Within 24 hours post-surgery (up to Day 2)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery.

Percentage of participants without nausea, defined as urge to vomit without the presence of expulsive muscular movements were reported. CMH method was used for analysis. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Absence of Nausea in the First 24 Hours Post-Surgery	34.1 percentage of participants Interval 0.196 to 0.487	48.7 percentage of participants Interval 0.33 to 0.644	—

SECONDARY outcome

Timeframe: Within 24 hours post-surgery (up to Day 2)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery.

Percentage of participants to whom rescue therapy was given as per local standard of care guidelines were reported. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants Requiring Rescue Therapy for Breakthrough PONV Within 24 Hours Post-Surgery	56.1 percentage of participants Interval 0.409 to 0.713	33.3 percentage of participants Interval 0.185 to 0.481	—

SECONDARY outcome

Timeframe: Within 24 hours post-surgery (up to Day 2)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery. Overall number analyzed are the number of participants with events.

Duration between end of wound closure to first emetic event i.e., vomiting or retching was reported. If a participant did not have an emetic event within 24 hours post-surgery, they were censored at 24 hours post-surgery. Cox proportional hazard model was used for analysis.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=10 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=4 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Time From End of Surgery to First Emetic Event	NA hours Median time to first event and full range are not estimable due to too few events within the 24 hours observation window.	NA hours Median time to first event and full range are not estimable due to too few events within the 24 hours observation window.	—

SECONDARY outcome

Timeframe: 30 minutes; 1, 2, 6, and 24 hours post-surgery (up to Day 2)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery. Overall number of participants analyzed are the participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.

VRS was used to score postoperative nausea on 11-point numerical scale. The score ranges from 0-10, where 0 represents 'no nausea' and 10 represents 'worst nausea possible'. Higher score represents worsening of disease. Mixed-effects model for repeated measures (MMRM) was used for analysis. Least square mean (LSM) estimates extracted from MMRM are presented in the data table for each time point.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=18 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=26 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Peak Nausea Verbal Rating Scale (VRS) Score 30 Minutes Post Surgery	0.159 score on a scale Standard Error 0.227	0.347 score on a scale Standard Error 0.184	—
Peak Nausea Verbal Rating Scale (VRS) Score 1 Hour Post Surgery	0.099 score on a scale Standard Error 0.254	0.500 score on a scale Standard Error 0.204	—
Peak Nausea Verbal Rating Scale (VRS) Score 2 Hours Post Surgery	0.043 score on a scale Standard Error 0.201	0.308 score on a scale Standard Error 0.162	—
Peak Nausea Verbal Rating Scale (VRS) Score 6 Hours Post Surgery	-0.020 score on a scale Standard Error 0.073	0.077 score on a scale Standard Error 0.059	—
Peak Nausea Verbal Rating Scale (VRS) Score 24 Hours Post Surgery	0.203 score on a scale Standard Error 0.142	0.000 score on a scale Standard Error 0.117	—

SECONDARY outcome

Timeframe: Within 24 hours post-surgery (up to Day 2)

Population: FAS included all participants who were randomized to treatment and received both doses of double-blind study drug before and during surgery.

Percentage of participants with total response, defined as no emesis, no nausea (VRS score \<1), and no need for rescue therapy were reported. VRS was used to score postoperative nausea on 11-point numerical scale, where 0 represents 'no nausea' and 10 represents 'worst nausea possible'. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=39 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Total Response	34.1 percentage of participants Interval 0.196 to 0.487	48.7 percentage of participants Interval 0.33 to 0.644	—

SECONDARY outcome

Timeframe: 1-3, 4-6, 7-9, 10-18, and 22-26 hours post-dose (up to Day 2)

Population: PK Set included all participants who received study drug and had at least 1 evaluable PK sample. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified timepoint. The data for this outcome measure was collected and reported separately for the participants who received the unintended mis-dose of TAK-951 redacted mg.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=20 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=18 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
TAK-951 Plasma Concentrations 22-26 Hours Post Dose	672.63 picograms per milliliter(pg/mL) Standard Deviation 699.161	—	—
TAK-951 Plasma Concentrations 1-3 Hours Post Dose	24734.50 picograms per milliliter(pg/mL) Standard Deviation 14782.359	58229.41 picograms per milliliter(pg/mL) Standard Deviation 42971.281	—
TAK-951 Plasma Concentrations 4-6 Hours Post Dose	18456.11 picograms per milliliter(pg/mL) Standard Deviation 13906.450	36950.00 picograms per milliliter(pg/mL) Standard Deviation 26649.650	—
TAK-951 Plasma Concentrations 7-9 Hours Post Dose	10568.31 picograms per milliliter(pg/mL) Standard Deviation 8140.684	17741.76 picograms per milliliter(pg/mL) Standard Deviation 9705.848	—
TAK-951 Plasma Concentrations 10-18 Hours Post Dose	4478.22 picograms per milliliter(pg/mL) Standard Deviation 2433.185	—	—

SECONDARY outcome

Timeframe: From first administration of study drug up to Day 14

Population: Safety Analysis Set (SAF) included all participants who were randomized to treatment and received both doses of double-blind study drug. The data for this outcome measure was collected and reported separately for the participants who received the unintended mis-dose of TAK-951 redacted mg.

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. A TEAE is defined as an AE with an onset that occurs after receiving study drug. Percentages are rounded off to whole number at the nearest single decimal.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=21 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC n=18 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Any Treatment Emergent Adverse Event (TEAE)	87.8 percentage of participants	71.4 percentage of participants	88.9 percentage of participants

SECONDARY outcome

Timeframe: From first administration of study drug up to Day 14

Population: SAF included all participants who were randomized to treatment and received both doses of double-blind study drug. The data for this outcome measure was collected and reported separately for the participants who received the unintended mis-dose of TAK-951 redacted mg.

Vital signs included heart rate, respiratory rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP), body temperature and BMI. Percentage of participants with markedly abnormal vital sign values were reported. Percentages are rounded off to whole number at the nearest single decimal. Only categories with at least 1 participant with data are reported.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=21 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC n=18 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Markedly Abnormal Vital Signs DBP (mmHg): High: >90	43.9 percentage of participants	14.3 percentage of participants	38.9 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Signs BMI (kg/m^2): High: >25.0	90.2 percentage of participants	85.7 percentage of participants	88.9 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Signs Heart Rate (beats per minute [beats/min]): Low: <60	36.6 percentage of participants	19.0 percentage of participants	22.2 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Signs Heart Rate (beats/min): High: >100	14.6 percentage of participants	66.7 percentage of participants	72.2 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Signs Respiratory Rate (breaths per minute [breaths/min]): Low: <12	46.3 percentage of participants	19.0 percentage of participants	55.6 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Signs Respiratory Rate (breaths/min): High: >16	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Signs SBP (millimeters of mercury [mmHg]): Low: <85	7.3 percentage of participants	9.5 percentage of participants	16.7 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Signs SBP (mmHg): High: >140	70.7 percentage of participants	42.9 percentage of participants	77.8 percentage of participants
Percentage of Participants With Markedly Abnormal Vital Signs DBP (mmHg): Low: <50	22.0 percentage of participants	33.3 percentage of participants	55.6 percentage of participants

SECONDARY outcome

Timeframe: From first administration of study drug up to Day 14

Population: SAF included all participants who were randomized to treatment and received both doses of double-blind study drug. The data for this outcome measure was collected and reported separately for the participants who received the unintended mis-dose of TAK-951 redacted mg. Overall number analyzed is the number of participants with data available for analyses. Clinical significance is based on PI determination.

Percentage of participants with clinically significant ECG interpretation were reported. Percentages are rounded off to whole number at the nearest single decimal. A combined ECG interpretation was derived using ECG heart rate, PR interval, RR interval, QRS duration, QT interval, and QT interval with Fridericia correction method (QTcF).

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=20 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC n=18 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Clinically Significant Electrocardiogram (ECG)	2.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: From first administration of study drug up to Day 14

Population: SAF included all participants who were randomized to treatment and received both doses of double-blind study drug. Number analyzed is the number of participants with data available for analysis for the specified category. The data for this outcome measure was collected and reported separately for the participants who received the unintended mis-dose of TAK-951 redacted mg.

Laboratory parameters included hematology and serum chemistry. Percentage of participants with markedly abnormal clinical laboratory values were reported. Percentages are rounded off to whole number at the nearest single decimal. Only categories with at least 1 participant with data are reported.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=41 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=21 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC n=18 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Erythrocytes (10^12 per liter [10^12/L]): Low: <0.8*Lower Limit of Normal (LLN)	14.6 percentage of participants	14.3 percentage of participants	27.8 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Hemoglobin (grams per liter [g/L]): Low: <0.8*LLN	14.6 percentage of participants	23.8 percentage of participants	11.1 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Hematocrit (percent [%]): Low: <0.8*LLN	12.2 percentage of participants	23.8 percentage of participants	11.1 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Aspartate Aminotransferase (units per liter[U/L]): High: >3*Upper Limit of Normal (ULN)	0.0 percentage of participants	4.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Alanine Aminotransferase (U/L): High: >3*ULN	0.0 percentage of participants	4.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Albumin (g/L): Low: <25	0.0 percentage of participants	4.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Protein (g/L): Low: <0.8*LLN	2.4 percentage of participants	4.8 percentage of participants	16.7 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Gamma Glutamyl Transferase (U/L): High: >3*ULN	0.0 percentage of participants	5.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Glucose (millimoles per liter [mmol/L]): Low: <3	0.0 percentage of participants	4.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Glucose (millimoles per liter [mmol/L]): High: >10	4.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Markedly Abnormal Clinical Laboratory Values Potassium (mmol/L): High: >5.5	2.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Within 6 hours post-surgery (Day 1)

Population: Immunogenicity Set included all participants who received at least 1 dose of study drug, had an ADA status assessment at baseline, and at least 1 postbaseline sample. Overall number analyzed is the number of participants with non-missing data for this outcome measure i.e., responders. The data for this outcome measure was collected and reported separately for the participants who received the unintended mis-dose of TAK-951 redacted mg.

Percentage of participants with ADA results as: ADA negative, ADA positive were reported. Participants with ADA positive status are defined as those who had confirmed positive ADA status in baseline or at least 1 postbaseline assessments. Participants with ADA negative status are defined as those who did not have positive ADA response at baseline and in all postbaseline assessments.

Outcome measures

Outcome measures
Measure	Ondansetron 4 mg IV n=14 Participants Participants received prophylaxis with ondansetron 4 mg, IV immediately before induction and TAK-951 placebo SC approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 4 mg SC n=14 Participants Participants received prophylaxis with ondansetron placebo IV immediately before induction and TAK 951 4 mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).	TAK-951 Redacted mg SC Participants received prophylaxis with ondansetron placebo IV immediately before induction and unintended mis-dose of TAK 951 redacted mg, SC, approximately 30 to 45 minutes before the end of surgery (wound closure).
Percentage of Participants With TAK-951 Antidrug Antibodies (ADA) Any Antidrug Antibody Positive	0.0 percentage of participants	0.0 percentage of participants	—
Percentage of Participants With TAK-951 Antidrug Antibodies (ADA) Any Antidrug Antibody Negative	100.0 percentage of participants	100.0 percentage of participants	—

Adverse Events

Ondansetron 4 mg IV

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

TAK-951 4 mg SC

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

TAK-951 Redacted mg SC

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER