Clinical trial NCT04557189: A Study of TAK-951 to Stop Adults Getting Nausea and Vomiting After Planned Surgery
Official title: A Randomized Double-Blind, Sponsor-Open, Double-Dummy, Proof of Concept Phase 2 Study to Evaluate the Efficacy and Safety of TAK-951 Versus Ondansetron in the Prophylaxis of Postoperative Nausea and Vomiting in High-Risk Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Nausea and Vomiting (PONV)
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-09-21
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: The drug being tested in this study is called TAK-951. TAK-951 is being tested for prophylaxis for postoperative nausea and vomiting in high-risk participants.

The study will enroll a maximum of 160 patients, to allow a sample size of up to approximately 100 participants who have received both doses of Double-blind study drug/matching placebo. Participants will be randomly assigned in a 1:1 ratio to either Treatment Group A or Treatment Group B which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* 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.

This trial will be conducted in the United States. The overall time to participate in the study from the time of surgery to completion is approximately 14 days. Participants will make multiple visits to the clinic and will be contacted by telephone after receiving their last dose of the drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Participants undergoing elective surgery under general anesthesia, expected to last for at least 1 hour from induction of anesthesia to wound closure.
2. Participants are expected to require or have agreed to stay, at least 1 overnight in the hospital.
3. Participants American Society of Anesthesiologists (ASA) physical status is ASA I-III.
4. Participants with 3 or more Apfel risk factors defined as:

   1. Female sex.
   2. Nonsmoking status (never smoked or stopped smoking ≥12 months ago).
   3. History of PONV or motion sickness.
   4. Planned use of postoperative opioid analgesics.

Exclusion Criteria:

1. Participants who are expected to remain intubated post-anesthesia.
2. 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.
3. 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.
4. 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.
5. Participants who have an allergy or contraindication to the recommended and available rescue therapy for the treatment of PONV.
6. Circumstance that, in the investigator's opinion, make participation in this clinical study inappropriate.
7. Participants found at the screening to have a QT interval with Fridericia correction method (QTcF) ≥450 msec or other factors that increase the risk of QT prolongation or arrhythmic events. Assessments showing bundle branch block and a prolonged QTcF should be discussed with the study monitor and the sponsor for potential inclusion.
8. 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).
9. Participants who have had 3 incidents of vasovagal syncope within the last 5 years.
10. 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.
11. 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.
12. Participants with a history of acute myocardial ischemia within the last 12 months.
13. 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.
14. 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.

Primary outcomes:
measure: Percentage of Participants With Complete Response in the Immediate Postoperative Period
timeFrame: 6 hours post-surgery (Day 1)
Secondary outcomes:
measure: Percentage of Participants With Complete Response Within 24 Hours Post-Surgery
timeFrame: Within 24 hours post-surgery (up to Day 2)
measure: Percentage of Participants With Emesis in the First 6 Hours Post-Surgery
timeFrame: Within 6 hours post-surgery (Day 1)
measure: Percentage of Participants With Emesis Within 24 Hours Post-Surgery
timeFrame: Within 24 hours post-surgery (up to Day 2)
measure: Percentage of Participants With Absence of Nausea in the First 6 Hours Post-Surgery
timeFrame: Within 6 hours post-surgery (Day 1)
measure: Percentage of Participants With Absence of Nausea in the First 24 Hours Post-Surgery
timeFrame: Within 24 hours post-surgery (up to Day 2)
measure: Percentage of Participants Requiring Rescue Therapy for Breakthrough PONV Within 24 Hours Post-Surgery
timeFrame: Within 24 hours post-surgery (up to Day 2)
measure: Time From End of Surgery to First Emetic Event
timeFrame: Within 24 hours post-surgery (up to Day 2)
measure: Peak Nausea Verbal Rating Scale (VRS) Score
timeFrame: 30 minutes; 1, 2, 6, and 24 hours post-surgery (up to Day 2)
measure: Percentage of Participants With Total Response
timeFrame: Within 24 hours post-surgery (up to Day 2)
measure: TAK-951 Plasma Concentrations
timeFrame: 1-3, 4-6, 7-9, 10-18, and 22-26 hours post-dose (up to Day 2)
measure: Percentage of Participants With Any Treatment Emergent Adverse Event (TEAE)
timeFrame: From first administration of study drug up to Day 14
measure: Percentage of Participants With Markedly Abnormal Vital Signs
timeFrame: From first administration of study drug up to Day 14
measure: Percentage of Participants With Clinically Significant Electrocardiogram (ECG)
timeFrame: From first administration of study drug up to Day 14
measure: Percentage of Participants With Markedly Abnormal Clinical Laboratory Values
timeFrame: From first administration of study drug up to Day 14
measure: Percentage of Participants With TAK-951 Antidrug Antibodies (ADA)
timeFrame: Within 6 hours post-surgery (Day 1)
Other outcomes:
Locations:
city: Sheffield
country: United States
facility: Helen Keller Hospital
state: Alabama
city: Pasadena
country: United States
facility: Lotus Clinical Research Inc
state: California
city: Tamarac
country: United States
facility: Phoenix Clinical Research
state: Florida
city: Stony Brook
country: United States
facility: Stony Brook Medicine - Hospital
state: New York
city: Bellaire
country: United States
facility: First Street Hospital - Research
state: Texas
city: Carrollton
country: United States
facility: Legent Orthopedic Hospital
state: Texas
city: Houston
country: United States
facility: Altus Houston Hospital - Hospital
state: Texas
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: