Clinical trial NCT00431236 (phase 3, status: completed)
Conditions: nausea and vomiting, chemotherapy-induced
ICD codes: D61.810
Drugs: oral casopitant (gw679769), iv casopitant (gw679769), iv ondansetron hydrochloride, oral dexamethasone
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Eligibility criteria:

        Inclusion criteria:

          -  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.

          -  Males or females of at least 18 years of age.

          -  Diagnosed with a malignant solid tumor and is scheduled to receive their first course
             of cytotoxic chemotherapy with cisplatin administered as a single intravenous dose of
             ≥ 70mg/m² over 1-4 hours on study Day 1, either alone or in combination with other
             chemotherapeutic agents. For combination regimens, non-cisplatin agents of moderate to
             high emetogenic potential will be allowed, but must be administered following the
             cisplatin infusion and be completed no more than 6 hours after the initiation of the
             cisplatin infusion. Chemotherapy agents of minimal to low emetogenic potential may be
             given on Day 1 following cisplatin or on any subsequent study day. Taxanes (e.g.
             paclitaxel, docetaxel) may be administered on study Day 1 only following cisplatin.

          -  Has an ECOG Performance Status of 0, 1, or 2.

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

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

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

               -  Bilirubin ≤ 1.5 x ULN

               -  Serum Creatinine ≤1.5 mg/dL (Standard units : ≤ 132.6 µMOL/L OR

               -  Creatinine clearance ≥ 60 mL/min

        Creatinine clearance must be calculated using the Cockcroft-Gault formula:

        Clcreat (ml/min) = (140-age [yr]) x body wt [kg] 72 x serum creatinine [mg/dl] For females:
        multiply creatinine clearance by a factor of 0.85. OR Clcreat (ml/min) = (140-age [yr]) x
        body wt [kg] serum creatinine [µmol/L] K=1.05 for females K=1.23 for males

          -  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
             a 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.

        obstruction

        Exclusion criteria:

          -  Has previously received cytotoxic chemotherapy. Previous biological or hormonal
             therapy will be permitted.

          -  Is scheduled to receive cisplatin treatment on more than one day during a single cycle
             of therapy.

          -  If female, is pregnant or lactating.

          -  Has received radiation therapy to the thorax, head & neck, abdomen, or the pelvis in
             the 10 days prior to receiving the first dose of study medication and/or will receive
             radiation therapy to the thorax, head & neck, abdomen or the pelvis in the 6 days
             following the first dose of study medication.

          -  Emesis (i.e. vomiting and/or retching) experienced in the 24 hours prior to receiving
             the first dose of study medication.

          -  Clinically significant nausea (e.g. ≥25 mm on a VAS) in the 24 hours prior to
             receiving the first dose of study medication.

          -  A known central nervous system primary or malignancy metastatic to the CNS, unless
             successfully treated with excision or radiation and subsequently has been stable for
             at least 1 week prior to receiving the first dose of study medication.

          -  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.

          -  An active systemic infection or any uncontrolled disease (other than malignancy)
             which, in the opinion of the investigator, may confound the results of the study or
             pose an unwarranted risk to the subject. Subjects with a previous, but not current,
             history of alcoholism may be permitted provided that, in the investigator's opinion,
             the subject's disease state will not confound the results of the study.

          -  Receiving or planning to receive a systemic corticosteroid therapy at any dose within
             72 hours prior to the first dose of study medication, except where indicated as
             premedication for a taxane. However, topical steroids and inhaled corticosteroids with
             a steroid dose of≤10 mg prednisone daily or its equivalent are permitted.

          -  Is scheduled to receive bone marrow transplantation and/or stem cell rescue with this
             course of cisplatin therapy.

          -  Has received an investigational drug within the 30 days or five half-lives (whichever
             is longer) prior to receiving the first dose of study medication, and/or is scheduled
             to receive any investigational drug during the study.

          -  Has received moderately and/or highly emetogenic medication within the 48 hours prior
             to the first dose of study medication. (Opioid narcotics for cancer pain will be
             permitted if the subject has been on such medication for at least 7 days and has not
             experienced nausea or emesis 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 GW679769 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 or pemetrexed therapy)

               -  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

               -  domperidone

               -  mirtazapine

               -  olanzapine

               -  cannabinoids

          -  Has taken/received strong or moderate inhibitors of CYP3A4 and CYP3A5 prior to
             administration of casopitant (GW679769) investigational product

          -  Has taken/received inducers of CYP3A4 and CYP3A5 within fourteen days prior to the
             administration of casopitant investigational product

          -  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

          -  Is currently taking or plans to take any of the following CYP3A4 substrates:
             astemizole, cisapride, pimozide, terfenadine.