Clinical trial NCT00366834 (phase 3, status: completed)
Conditions: vomiting, nausea, nausea and vomiting, chemotherapy-induced
ICD codes: R11.10, R11.12, R11.14, R11.11, K91.0, O21.2, O21.8, R11.0, R11.11, R11.2, D61.810
Drugs: casopitant (gw679769) oral tablets, casopitant (gw679769) intravenous, dexamethasone intravenous, ondansetron oral tablets, placebo
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Eligibility criteria:

        Inclusion criteria:

          -  A subject will be considered eligible for inclusion in this study only if all of the
             following criteria apply:

          -  Subject understands the nature and purpose of this study and the study procedures and
             has signed an informed consent form for this study to indicate this understanding.

          -  At least 18 years of age.

          -  Is scheduled to receive their first course of an anthracycline and cyclophosphamide
             containing moderately emetogenic chemotherapy regimen for the treatment of a solid
             malignant tumor as outlined in Section 8.1.1.

          -  Has an ECOG performance status of 0, 1, or 2.

          -  Hematologic and metabolic status must be adequate for receiving a moderately
             emetogenic regimen and meet the following criteria:

               -  Total Neutrophils ≥ 1500/mm³(Standard units : ≥1.5 x 10^9/L)

               -  Platelets ≥ 100,000/mm³ (Standard units: ≥100.0 x 10^9/L)

               -  Bilirubin ≤ 1.5 x ULN

               -  Liver enzymes must be below the following limits:

                    -  Without known liver metastases: Aspartate aminotransferase (AST) and/or
                       alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal.

                    -  With known liver metastases: AST and/or ALT ≤ 5.0 x upper limit of normal.

          -  Is willing and able to complete daily components of the subject diary for each study
             cycle.

          -  Women of childbearing potential; must commit to consistent and correct use of an
             acceptable method of birth control; GSK acceptable contraceptive methods, when used
             consistently and in accordance with both the product label and the instructions of a
             physician, are as follows:

               1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant,
                  including any female who is post-menopausal. For purposes of this study,
                  postmenopausal is defined as one year without menses)

               2. child-bearing potential: must have a negative serum pregnancy test result or
                  negative urine dipstick pregnancy test within 24 hours prior to the first dose of
                  investigational product of Cycle 1, Day 1 and agrees to one of the following:

                    -  male partner who is sterile prior to the female subject's entry into the
                       study and is the sole sexual partner for that female subject

                    -  oral contraceptives (e.g., oral, injectable, or implantable) with
                       double-barrier method of contraception consisting of spermicide with either
                       condom or diaphragm for a period after the trial to account for potential
                       drug interaction (minimum of six weeks)

                    -  double-barrier method of contraception consisting of spermicide with either
                       condom or diaphragm

                    -  intra-uterine device (IUD) with a documented failure rate of less than 1%
                       per year

                    -  complete abstinence from intercourse for two weeks before exposure to the
                       investigational product throughout the clinical trial, and for a period
                       after the trial to account for elimination of the drug (minimum of three
                       days),

                    -  if subjects indicate they will remain abstinent during the period described
                       above, they must agree to follow GSK guidelines for the consistent and
                       correct use of an acceptable method of birth control should they become
                       sexually active.

        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.