Pilot Study to Assess Palonosetron Versus Ondansetron as Rescue Medication in Subjects That Develop Postoperative Nausea and Vomiting (PONV) in the Postanesthesia Care Unit (PACU)

Study Overview
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Brief Summary
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The purpose of this study is to investigate palonosetron versus ondansetron as rescue medication in subjects that develop postoperative nausea and vomiting (PONV) in the Postanaesthesia Care Unit (PACU).

Detailed Description
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Postoperative nausea and vomiting (PONV) is a frequent complication of surgery, which can lead to subject discomfort and dissatisfaction as well as considerable subsequent medical and economic consequences. In this multi-center, open-label, parallel, randomized, pilot study, outpatient surgical patients who experience post-operative nausea or vomiting in the PACU will be stratified by gender and randomly assigned to either palonosetron HCl 0.075 mg IV or ondansetron 4 mg IV in a minimization random allocation. Male or female outpatients, scheduled for elective laparoscopic abdominal or gynecological surgery under general endotracheal anesthesia will be enrolled. All subjects will be asked to attend 2 visits to the study center: Screening (Days -14 to -1) Treatment (Day 1, the day of the surgical procedure and randomization) Subjects treated will receive a follow-up telephone call by the Study Coordinator on Study Day 4 or 5 to review the subject diary for completion, to review adverse events, and concomitant medications, prior to the subject returning the completed diary to the site. At the Screening visit, subjects who provide their informed consent will undergo a clinical assessment. Demographic and baseline characteristics, including entrance criteria determination, medical history, history of PONV and/or currently prone to motion sickness, smoking status, prior and concomitant medication, physical examination, and vital signs will be documented. On the day of surgery, all subjects who meet the eligibility criteria will be prophylactically treated prior to anesthesia with ondansetron 4 mg IV, as preoperative antiemetic treatment. As clinically indicated for rescue therapy, subjects experiencing a nausea severity score ≥4 on the 11-point NRS, vomiting, or indicating a subject request will receive blinded study medication as their first line rescue therapy for PONV while in the PACU and no more than 6 hours after PACU admission. Subjects requiring rescue medication need to be dosed within 10 minutes of identifying the need for rescue medication. In an effort to ensure that this timeline is not exceeded, the sites will be allowed to randomize the subject prior to surgery, on the day of surgery. Subjects who are randomized but do not require rescue therapy and therefore not dosed with study drug, will be considered 'Subjects randomized but not treated'. Subject diaries will be used to record the date and time of study drug administration, the reason for administering rescue medication, baseline emetic symptoms immediately prior to administration of rescue medication, the occurrence of emetic episodes, the severity and duration of nausea, and subject functioning evaluations for nausea and emesis assessed according to the modified Osoba questionnaire (Martin et. al. 2003). The baseline assessment that is performed just prior to administering the rescue medication must indicate that at least one of the following conditions was met: the subject had a nausea severity score ≥4 on the 11-point (0-10) NRS vomiting subject request: subject request must be approved by site staff and must be based on either nausea or emesis symptoms

Official Title
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A Multi-Center, Open-Label, 2-Arm, Randomized, Stratified, Parallel, Pilot Study to Assess Palonosetron vs. Ondansetron as Rescue Medication in Subjects That Develop Postoperative Nausea and Vomiting (PONV) in the Postanesthesia Care Unit (PACU)

Conditions
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Postoperative Nausea and Vomiting

Intervention / Treatment
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* Drug: Ondansetron
* Drug: Palonosetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female >=18 years of age. American Society of Anesthesiologists (ASA) physical status 1 to 3. Presence of at least 2 of the following PONV risk factors: female gender history of PONV and/or currently prone to motion sickness (if the subjects cannot remember their last experience of motion sickness or if they suffered from it as a child, then they will not be classified as prone) non-smoking status (never smoked or quit >=12 months ago) Outpatient undergoing elective laparoscopic gynecological or abdominal surgery Surgery for which anesthesia is expected to last at least 30 minutes General endotracheal anesthesia conducted as outlined in the anesthetic procedures section of the protocol If a subject has a known hepatic, renal or cardiovascular impairment, he/she may be enrolled in this study at the discretion of the Investigator If a subject has or may develop prolongation of cardiac conduction intervals, particularly QTc, he/she may be enrolled at the discretion of the Investigator. If a subject is female of childbearing potential, she must be using reliable contraceptive measures and have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours prior to surgery on Day 1. Reliable contraceptive measures include implants, injectables, combined oral contraceptives, some intrauterine devices, vasectomized partner or sexual abstinence. Non-childbearing potential is defined as post-menopausal for at least 2 years or documented surgical sterilization or hysterectomy at least 3 months before study start. Exclusion Criteria: Inability to understand or cooperate with the study procedures as determined by the Investigator. Women who are pregnant, nursing or planning to become pregnant, are not using effective birth control, or that have had a positive serum pregnancy test within 72 hours prior to surgery on Day 1. A cancer patient who has had chemotherapy within 4 weeks prior to study entry (Screening visit). Any kind of emetogenic radiotherapy within 8 weeks prior to study entry (Screening visit). Has received any investigational drugs within 30 days before study entry. Having taken any drug with potential antiemetic efficacy within 24 hours prior to anesthetic procedures. Any vomiting, retching, or nausea in the 24 hours preceding the administration of anesthesia . Body mass index (BMI) > 40. Known or suspected current history of alcohol abuse or drug abuse. Known hypersensitivity/contraindication to 5-HT3 antagonists or study drug excipients. Epileptic patients. Any condition, which in the opinion of the Investigator would make the subject ineligible for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Ondansetron<br>* Subjects will receive ondansetron 4 mg intravenously (IV) and will be followed for 72 hours. Ondansetron is a selective 5-HT3 receptor antagonist. It is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin and prevention of postoperative nausea and/or vomiting.<br>* Other names: Zofran;|
| Active Comparator: 2<br> | Drug: Palonosetron<br>* Subjects will receive palonosetron HCl 0.075 mg IV and will be followed for 72 hours. Palonosetron hydrochloride (Aloxi®) is a potent and selective 5-HT3 receptor antagonist for the prevention of acute nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy, the prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy, and the prevention of postoperative nausea and vomiting for up to 24 hours following surgery.<br>* Other names: Aloxi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Control | Complete control was defined as participants with no emetic episode, no rescue medication, and no more than 3 on the nausea numeric rating scale (NRS) severity score. The 11-point NRS scale (ranging from 0-10), where 0 means no nausea, 2 or 3 was mild nausea, around 5 was moderate nausea, 7 and higher was severe nausea and 10 means the worst possible nausea. Higher scores were considered as worse outcome. | Up to 72 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response | Complete response was defined as participants with no emetic episode and no use of rescue medication. An emetic episodic is defined as any number of retches (unproductive emesis) in a single 5-minute period; 1 or a sequence of vomits in a close succession not relieved by a period of relaxation of at least 2 minutes; or retching of less than (<) 5 minutes duration combined with a single vomit. | Up to 72 hours postdose | 
| Percentage of Participants Who Did Not Experience Any Episode of Emesis |  | Up to 72 hours postdose | 
| Percentage of Participants Who Did Not Receive Any Rescue Medication Post-surgical Procedure |  | Up to 72 hours postdose | 
| Change From Baseline in Nausea Severity Score | Severity of nausea was assessed at specific time points using an 11-point NRS scale (ranging from 0-10) for evaluation of nausea severity. On the 0-10 rating scale, 0 means no nausea, 2 or 3 was mild nausea, around 5 was moderate nausea, 7 and higher was severe nausea and 10 means the worst possible nausea. Higher scores were considered as worse outcome. | Baseline up to 72 hours postdose | 
| Modified Osoba Nausea and Emesis Module Questionnaire Score | Modified Osoba nausea and emesis module questionnaire was used to assess the impact of nausea and emesis on functional interference at 24, 48 and 72 hours postdose. The modified Osoba questionnaire included specific questions regarding the interference of nausea and emesis in daily activities (appetite, sleep, physical activities, social life, and enjoyment of life) with respective choices. The raw score of the modified Osoba questionnaire was the arithmetic mean of the non-missing item scores, using 1 for the answer not at all, 2 for the answer a little, 3 for the answer quite a bit, and 4 for the answer very much. Raw score range from 5-20 and the total score was computed by linearly transformed the raw score to final score range as 0 to 100 by calculating ([RS-1]/range)*100, with RS being the raw score and range being 3 in this case of answers scored from 1 to 4. Lower scores indicate better quality of life. | 24, 48 and 72 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PONV, rescue