Granisetron Transdermal Patch for Prevention of Postoperative Nausea and Vomiting

Patients will be recruited from the surgical population undergoing preoperative evaluation in
Anesthesiology Preoperative Evaluation Clinic at Hershey Med. Ctr. (~15,000 per year).
Selected patients (ASA 1-3, N=60) with history of severe PONV after one or more of previous
general anesthesia, and scheduled to undergo surgical procedures with general anesthesia will
be enrolled into IRB approved protocol. The patch will be placed by the patient at home 24 -
48 hours before surgery as directed by the doctor. The subsequent standardized general
anesthesia protocol for elective surgery will include general endotracheal anesthesia with
sevofluran, including standard intraoperative PONV prophylaxis (IV dexamethasone and IV
ondansetron, each 4 mg). Postoperative evaluation will include recording of incidence and
severity of PONV at the time of discharge from PACU (acute PONV), at 24 hr, 48 hrs, 72 and
120 hrs (delayed or post discharge PONV).

7.2.1 Visit 1 - Anesthesia Preoperative Evaluation Clinic and recruitment and drug
dispensation Patient is seen in clinic and identified as having a history of serious PONV, in
particular delayed or post discharge PONV. Study will be explained to the patient and consent
obtained. The investigational pharmacy will be notified that a study patient has been
enrolled and they will prepare the patches for distribution to the patient.

A member of the research team will obtain the assigned patches from the investigational
pharmacy and deliver to the anesthesia provider (member of the research team).

The provider will then demonstrate to the patient how to apply the patch and the patient can
practice using a placebo patch to show that the correct placement. Patient will then take the
actual patch home with them.

7.2.2 Visit 2 - approximately 24-48 hours preoperatively (patient's home) Patient will apply
the patch to their upper arm 24-48 hours before scheduled surgical procedure, as instructed
during their pre-op anesthesia visit. The patch will then remain in place until 120 hours
after surgical procedure. No backup patch will be provided so the patients with the
accidently missing patch will need to call their primary surgical service for the standard
antiemetic medication.

7.2.3 Visit 3- Day of Surgery Patient will arrive for surgery. A member of the research team
will meet them in the SDU and record the time that the patch was applied, and if it has been
placed correctly, intact and still in place. Any potential side effects (systemic or local)
will be recorded at that time. The subsequent standardized general anesthesia protocol for
elective surgery will include general endotracheal anesthesia with sevofluran (no nitrous
oxide), muscle relaxants (with reversal), intraoperative IV opioid analgesics, including
standard PONV prophylaxis (dexamethasone and ondansetron IV 4 mg).

Early postoperative evaluation will include recording of incidence and severity of PONV at
the time of discharge from PACU (acute PONV). The incidence of vomiting or retching will
recorded by the nursing staff. Patients with symptoms requiring a rescue antiemetic—nausea
score ≥4 on an 11-point Numeric Rating Scale (NRS), retching or vomiting, or patient
request—within 6 hours of PACU admission will be given the rescue medication (Benadryl or
promethazine). The NRS was an 11-point linear scale on which patients rated their nausea,
with 0 meaning no nausea and 10 meaning the worst possible nausea.

The subsequent evaluations will be performed either at the patient's bed (if in the hospital)
or by phone call at 24 hr, 48 hrs, 72 and 120 hrs (delayed or post discharge PONV). The
patient will be supplied with a diary to record the information that will be requested on the
follow-up phone calls.

The primary efficacy endpoint will be complete response (CR), defined as no emetic episode
and no rescue medication; the proportions of patients with no emesis and no additional rescue
medication in the 120 hours following the completion of surgical procedure and the change
from baseline nausea score using the NRS. Treatment-emergent adverse events (TEAEs),
regardless of suspected causal relationship to the study medication, will be also recorded
throughout and continued until 5 days after surgery.

7.3 Duration of Participation Patient will remain in the study until all time points have
been met (maximum 5 days following surgery or 120 hours). At the end of the study the patient
will remove and dispose the remaining patch.

Inclusion Criteria:

- Patients that are between the ages of 18 and 89

- Scheduled to undergo surgical procedures with general anesthesia

- Seen in the anesthesia clinic at least 24 hours before surgery

- History of severe PONV after previous general anesthesia

- Surgical procedures with anticipated duration > 1 hour and no more than 5 hours

- American Society of Anesthesiologists (ASA) physical status I to III

Exclusion Criteria:

- Allergy to granisetron or other 5HT3RA drugs

- Previous allergic reactions to any drug skin patches

- Recent (less than 1 month) or current chemo- or radiotherapy

- Any nausea, vomiting, or retching within 24 hours prior to anesthesia

- Any type of eye surgeries

- History or diagnosis of gastrointestinal obstruction or ileus

- History of serotonin syndrome

- Unable to sign consent