Intravenous And Oral Casopitant (GW679769) For The Prevention Of Chemotherapy Induced Nausea And Vomiting

Exclusion Criteria

• •Has previously received cytotoxic chemotherapy. A history of previous biological or hormonal therapy will be permitted.
• •Is a female subject who is pregnant or lactating.
• •Has received radiation therapy to the brain, abdomen, or pelvis in the ten days prior to the first dose of study medication or casopitant investigational product and/or will receive radiation therapy to the brain, abdomen, or the pelvis in the six days following the first dose of study medication (ZOFRAN and dexamethasone) or casopitant investigational product.
• •Is scheduled to receive taxane therapy during cycle 1. Note that subjects will be permitted to receive taxane therapy in conjunction with one of the allowed MEC regimens during subsequent cycles.
• •Has experienced emesis (i.e., vomiting and/or retching) or clinically significant nausea in the 24 hours preceding the first dose of study medication or casopitant investigational product.
• •Has a known central nervous system primary or metastatic malignancy, unless successfully treated with excision or radiation and has been medically stable for at least 1 week prior to receiving the first dose of study medication or casopitant investigational product.
• •Has history of documented peptic ulcer disease (via endoscopy or x-ray), active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, or any uncontrolled medical condition (other than malignancy) which in the opinion of the Investigator may confound the results of the study, represent another potential etiology for emesis and nausea (other than CINV) or pose an unwarranted risk to the subject.
• •Has a known hypersensitivity or contraindication to ZOFRAN, another 5-HT3 receptor antagonist, dexamethasone, or any component of casopitant.
• •Has previously received an NK-1 receptor antagonist.
• •Received an investigational drug in the previous 30 days or is scheduled to receive any investigational drug other than casopitant during the study period.
• •Has taken/received any medication of moderate or high emetogenic potential within the 48 hours prior to the first dose of study medication or casopitant investigational product. Opioid narcotics for cancer pain will be permitted if the subject has been on a stable dose and has not experienced emesis or nausea from the narcotics.
• •Has taken/received any medication with known or potential antiemetic activity within the 24-hour period prior to receiving study drug. This includes, but is not limited to:
• •* 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron). Palonestron is not permitted within 7 days prior to administration of investigational product.
• •* benzamide / benzamide derivatives (e.g., metoclopramide, alizapride)
• •* benzodiazepines (except if the subject is receiving such medication for sleep or anxiety and has been on a stable dose for at least seven days prior to the first dose of casopitant investigational product; however, lorazepam is prohibited 24 hours prior to receiving study drug regardless of reason for use)
• •* phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine)
• •* butyrophenone (e.g., haloperidol, droperidol)
• •* corticosteroids (e.g., dexamethasone, methylprednisolone; with the exception of topical steroids for skin disorders, inhaled steroids for respiratory disorders, and prophylactic treatment for taxane therapy during subsequent cycles)
• •* anticholinergics (e.g., scopolamine, with the exception of inhaled anticholingerics for respiratory disorders e.g., ipratropium bromide)
• •* antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine), except for prophylactic use for taxane therapy during cycle 2-4
• •* domperidone
• •* cannabinoids
• •* mirtazpine
• •* olanzapine
• •Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 for a specified period prior to administration of casopitant investigational product (see Section 8.2.1 "Inhibitors of CYP3A4 and CYP3A5")
• •Has taken/received inducers of CYP3A4 and CYP3A5 within fourteen days prior to the administration of casopitant investigational product. (see Section 8.2.2 "Inducers of CYP3A4 and CYP3A5")
• •Is taking the anti-diabetic agent repaglinide or the diuretic torsemide. Investigators are advised to exercise caution if including patients taking the anti-diabetic agents rosiglitazone or pioglitazone, or antimalarial agents such as chloroquine and amodiaquine, as the metabolite of casopitant is a potential inhibitor of CYP2C8 (See Section 8.2.3 "Substrates for CYP2C8" and Section 8.4 "Necessary Caution with CYP2C8 Substrates").
• •Is currently taking or plans to take the any of the following CYP3A4 substrates: astemizole, cisapride, pimozide, terfenadine.