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)

Condition(s) targeted: Postoperative Nausea and Vomiting

Intervention: ondansetron (Drug); palonosetron (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Eisai Inc.

Official(s) and/or principal investigator(s):
David Cox, Study Director, Affiliation: Eisai Inc.

Overall contact:
Eisai Medical Services, Phone: 1-888-422-4743

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 postanesthesia care unit (PACU).

Official title: 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)

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Proportion of subjects with Complete Control (CC)

Secondary outcome:

Proportion of subjects with a Complete Response (CR)

Proportion of subjects with no emesis

Proportion of subjects with no rescue medication

Change from baseline nausea score using an 11-point Numeric Rating Scale (NRS). Impact of nausea and emesis on Functional Interference.

Detailed description: 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:

1. Screening (Days - 14 to -1)

2. 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:

1. the subject had a nausea severity score ≥4 on the 11-point (0-10) NRS

2. vomiting

3. subject request: subject request must be approved by site staff and must be based on either nausea or emesis symptoms

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria

1. Male or female ≥18 years of age.

2. American Society of Anesthesiologists (ASA) physical status 1 to 3.

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)

4. Outpatient undergoing elective laparoscopic gynecological or abdominal surgery.

5. Surgery for which anesthesia is expected to last at least 30 minutes.

6. General endotracheal anesthesia conducted as outlined in the anesthetic procedures section of the protocol.

7. 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.

8. 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.

9. 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:

1. Inability to understand or cooperate with the study procedures as determined by the Investigator.

2. 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.

3. A cancer patient who has had chemotherapy within 4 weeks prior to study entry (Screening visit).

4. Any kind of emetogenic radiotherapy within 8 weeks prior to study entry (Screening visit).

5. Has received any investigational drugs within 30 days before study entry.

6. Having taken any drug with potential antiemetic efficacy within 24 hours prior to anesthetic procedures.

7. Any vomiting, retching, or nausea in the 24 hours preceding the administration of anesthesia.

8. Body mass index (BMI) > 40.

9. Known or suspected current history of alcohol abuse or drug abuse.

10. Known hypersensitivity/contraindication to 5-HT3 antagonists or study drug excipients.

11. Epileptic patients.

12. Any condition, which in the opinion of the Investigator would make the subject ineligible for participation in the study.

Eisai Medical Services, Phone: 1-888-422-4743

Precision Trials, Phoenix, Arizona 85032, United States; Recruiting

Accurate Clinical Trials, Inc, Laguna Hills, California 92653, United States; Recruiting

University of California San Francisco, San Francisco, California 94115, United States; Not yet recruiting

Stanford University, Stanford, California 94305, United States; Not yet recruiting

University of Miami- Jackson Memorial Hospital, Miami, Florida 33136, United States; Not yet recruiting

Advanced Surgical Associates, Miami, Florida 33133, United States; Not yet recruiting

University of Kansas Medical Center, Kansas City, Kansas 66160, United States; Not yet recruiting

Duke University Medical Center, Durham, North Carolina 27710, United States; Not yet recruiting

Ohio State University Medical Center, Columbus, Ohio 43210, United States; Not yet recruiting

Scott and White Hospital, Temple, Texas 76508, United States; Recruiting

Starting date: July 2009
Last updated: August 27, 2009