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

NCT04557189 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: TAK-951-2001
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 7

Brief Summary

Some adults are at a higher risk of feeling sick (nausea) or being sick (vomiting) after they have surgery. In this study, these adults will have planned surgery. The main aim of this study is to learn if TAK-951 stops these adults from getting nausea or vomiting after surgery. This will be compared with another medicine called ondansetron. Another aim is to check for side effects from the study medicines. Before surgery, the study doctor will check who can take part in this study. Those who can take part will be picked for either Treatment Group A or Treatment Group B by chance.

• Treatment Group A: Just before surgery, participants will receive a placebo slowly through a vein (infusion). Just before the end of the surgery, they will receive TAK-951 as an injection under the skin.
• Treatment Group B: Just before surgery, participants will receive ondansetron slowly through a vein (infusion). Just before the end of the surgery, they will receive a placebo as an injection under the skin. In this study, a placebo will look like TAK-951 but will not have any medicine in it. Participants will not know which study medicines they received, or in which order, nor will their study doctors or surgeons. This is to help make sure the results are more reliable. Participants will stay in the hospital for 24 hours after their surgery so that the study doctors can check for nausea and vomiting. The study doctors will also check for side effects from the study medicines. Participants will visit the hospital for a check-up 14 days later.

Conditions

Postoperative Nausea and Vomiting (PONV)

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Complete Response in the Immediate Postoperative Period

  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.

  6 hours post-surgery (Day 1)

Secondary Outcomes (15)

• Percentage of Participants With Complete Response Within 24 Hours Post-Surgery

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

• Percentage of Participants With Emesis in the First 6 Hours Post-Surgery

  Within 6 hours post-surgery (Day 1)

• Percentage of Participants With Emesis Within 24 Hours Post-Surgery

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

• Percentage of Participants With Absence of Nausea in the First 6 Hours Post-Surgery

  Within 6 hours post-surgery (Day 1)

• Percentage of Participants With Absence of Nausea in the First 24 Hours Post-Surgery

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

Study Arms (2)

Ondansetron 4 mg IV

EXPERIMENTAL

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).

Drug: Ondansetron; Drug: TAK-951 Placebo

TAK-951 4 mg SC

EXPERIMENTAL

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).

Drug: TAK-951; Drug: Ondansetron Placebo

Interventions

TAK-951 DRUG

TAK-951 SC injection

TAK-951 4 mg SC

Ondansetron DRUG

Ondansetron IV injection

Ondansetron 4 mg IV

Ondansetron Placebo DRUG

Ondansetron placebo-matching IV injection

TAK-951 4 mg SC

TAK-951 Placebo DRUG

TAK-951 placebo-matching SC injection

Ondansetron 4 mg IV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants undergoing elective surgery under general anesthesia, expected to last for at least 1 hour from induction of anesthesia to wound closure.
• Participants are expected to require or have agreed to stay, at least 1 overnight in the hospital.
• Participants American Society of Anesthesiologists (ASA) physical status is ASA I-III.
• Participants with 3 or more Apfel risk factors defined as:
• Female sex.
• Nonsmoking status (never smoked or stopped smoking ≥12 months ago).
• History of PONV or motion sickness.
• Planned use of postoperative opioid analgesics.

You may not qualify if:

• Participants who are expected to remain intubated post-anesthesia.
• Participants who experience nausea or vomiting within 24 hours before surgery or are diagnosed with gastroparesis, cyclic vomiting syndrome, or other condition associated with acute or chronic nausea and vomiting.
• Participants who have received, or are expected to receive, any excluded drug preoperatively within 24 hours before induction, during surgery, or within 24 hours after surgery.
• Participants scheduled to receive neuraxial anesthesia (e.g., epidural, spinal, or caudal anesthesia), regional blocks, or total IV anesthesia, and/or planned to receive different drugs for premedication, induction, maintenance, or reversal of anesthesia than those specified in the protocol.
• Participants who have an allergy or contraindication to the recommended and available rescue therapy for the treatment of PONV.
• Circumstance that, in the investigator's opinion, make participation in this clinical study inappropriate.
• Participants who have a direct family history of premature sudden death or channelopathy, personal history of Brugada syndrome (right bundle branch block pattern with ST elevation in leads V1-V3), long QT, short QT, arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy or catecholaminergic polymorphic ventricular tachycardia (VT).
• Participants who have had 3 incidents of vasovagal syncope within the last 5 years.
• Participants with an average heart rate (HR) \<55 or \>100 bpm or systolic blood pressure (SBP) \<90 mm Hg or Diastolic blood pressure (DBP) \<60 mm Hg during screening or prior to randomization on the day of surgery.
• Participants with a clinically significant ECG abnormality indicative of acute cardiac instability as determined by the investigator at screening, including more than first-degree atrioventricular block, nonsustained or sustained VT, or ECG changes consistent with acute myocardial ischemia or infarction.
• Participants with a history of acute myocardial ischemia within the last 12 months.
• Participants receiving beta-blockers chronically or between screening and surgery that cannot be safely withheld on the day of surgery in the investigator's judgment. Participants receiving certain other cardiovascular medications, such as vasodilators for hypertension, chronically or between screening and surgery that in the investigator's judgment cannot be adequately managed in the perioperative setting considering the potential vasodilatory effects of TAK-951 and anesthesia standard of care. The investigators must consult with the medical monitor regarding the eligibility of participants who are receiving beta-blockers, vasodilators, and other classes of medications that act on HR or BP.
• Participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 times the upper limit of normal (ULN) or total bilirubin \>1.5 times the ULN.

Sponsors & Collaborators

• Takeda: lead

Study Sites (7)

Helen Keller Hospital

Sheffield, Alabama, 35660, United States

Location

Lotus Clinical Research Inc

Pasadena, California, 91105, United States

Location

Phoenix Clinical Research

Tamarac, Florida, 33321, United States

Location

Stony Brook Medicine - Hospital

Stony Brook, New York, 11794, United States

Location

First Street Hospital - Research

Bellaire, Texas, 77401, United States

Location

Legent Orthopedic Hospital

Carrollton, Texas, 75006, United States

Location

Altus Houston Hospital - Hospital

Houston, Texas, 77072, United States

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Postoperative Nausea and Vomiting

Interventions

Ondansetron

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nausea; Signs and Symptoms, Digestive; Signs and Symptoms; Vomiting

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: September 21, 2020
• Study Start: October 20, 2020
• Primary Completion: March 7, 2022
• Study Completion: March 21, 2022
• Last Updated: April 21, 2023
• Results First Posted: April 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (7)