Phase II Proof-of-concept Study of APD421

Inclusion criteria

• Male or female patients ≥ 18 years of age
• Ability and willingness to give written informed consent
• Patients scheduled to receive, on day 1 of their chemotherapy, a first cisplatin chemotherapy infusion at a dose of 50 mg/m2 or greater
• Karnofsky performance score ≥ 60%
• Adequate cardiac, hepatic and renal function

• QTc interval < 500 ms
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 5 x upper limit normal (ULN)
• Bilirubin < 3 x ULN
• Creatinine < 2 x ULN
• Adequate haematological function

• Haemoglobin ≥ 9 g/dL
• White blood count ≥ 3.0 x 109/L
• Platelet count ≥ 100 x 109/L
• For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (e.g., abstinence from sexual intercourse, surgical sterilisation (of subject or partner) or a double-barrier method of contraception such as either an intra-uterine device (IUD) or an occlusive cap with spermicide, in conjunction with partner's use of a condom) during the study and for a period of at least 48 hours afterwards.

Exclusion criteria

• Patients scheduled to receive, prior to or in the 24 hours after cisplatin, any chemotherapeutic agent with a high or moderate emetic risk, see Appendix 4.
• Patients scheduled to receive paclitaxel or docetaxel
• Patients undergoing abdominal or pelvic irradiation within 48 hours prior to screening or scheduled to receive abdominal or pelvic irradiation between screening and 24 hours after cisplatin administration
• Patients receiving APD421 for any indication within the last 2 weeks
• Patients who are allergic to APD421 or any of the excipients of APD421
• Patients with a pre-existing vestibular disorder
• Patients being treated with regular anti-emetic therapy including corticosteroids
• Patients receiving inhaled corticosteroids, unless started more than one month prior to the expected date of study entry
• Patients being treated with medications which could induce torsades de pointes, including Class Ia antiarrhythmic agents such as quinidine, disopyramide, procainamide; Class III antiarrhythmic agents such as amiodarone and sotalol; and other medications such as bepridil, cisapride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin
• Patients being treated with xxx
• Patients receiving benzodiazepines, unless on a stable dose for at least one month prior to the expected date of study entry
• Patients with pre-existing nausea or vomiting in the 24 hours before receiving cisplatin chemotherapy, e.g. anticipatory emesis
• Patients who are pregnant or breast feeding
• Patients with a history of alcohol abuse
• Patients with pre-existing, clinically significant cardiac arrhythmia
• Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study
• Patients who have participated in another study within the previous 28 days