Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients.
BACKGROUND
In recent years, there has been an increased interest in using a multimodal approach with combined agents to treat postoperative nausea and vomiting. This study evaluated whether the addition of an oral dose of the neurokinin-1 receptor antagonist casopitant improved the antiemetic efficacy of an intravenous dose of ondansetron hydrochloride.


METHODS
The authors enrolled 702 premenopausal or perimenopausal, nonsmoking, female patients aged 18-55 yr with a history of postoperative nausea and vomiting and/or motion sickness undergoing a laparoscopic or laparotomic gynecologic surgical procedure or laparoscopic cholecystectomy with general anesthesia. Subjects were randomized to one of five treatment arms: standard ondansetron 4 mg with casopitant at 0, 50, 100, or 150 mg, or 0 mg ondansetron with casopitant at 150 mg (the latter arm was considered an exploratory study group and was included in the safety analysis but not in the efficacy analysis).


RESULTS
A significantly greater proportion of patients in all of the active casopitant plus ondansetron groups achieved a complete response (i.e., no vomiting, retching, rescue medication, or premature withdrawal) during the first 24 h postoperatively versus those in the ondansetron-alone group (59-62% vs. 40%, respectively; P = 0.0006). All active doses seemed to be well tolerated; headache, dizziness, and constipation were the most frequently reported adverse events.


CONCLUSIONS
Compared with ondansetron alone, the casopitant and ondansetron combination results in superior emesis prevention during the first 24 h postoperatively in female patients with known risk factors for postoperative nausea and vomiting.
Lotus Clinical Research Inc, Huntington Hospital, Pasadena, California 91105, USA. neil@lotuscr.com
Neil K
NK
Singla
Sonia K
SK
Singla
Frances
F
Chung
Demetrios J
DJ
Kutsogiannis
Linda
L
Blackburn
Stephen R
SR
Lane
Jeremey
J
Levin
Brendan
B
Johnson
Joseph V
JV
Pergolizzi
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000768:Anesthesia, General / Q000379:methods; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects; D017081:Cholecystectomy, Laparoscopic; D003248:Constipation / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D013509:Gynecologic Surgical Procedures; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control*; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult; D014508:Urea
D000932:Antiemetics; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron; D010879:Piperazines; D010880:Piperidines; C531951:casopitant; D014508:Urea