A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam in Patients With ALK-positive Advanced Tumors

Exclusion Criteria

• •Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate), midazolam and warfarin as described in the local product information.
• •History of carcinomatous meningitis.
• •Presence or history of a malignant disease other than an ALK-positive advanced tumor that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
• •Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
• •Unstable angina within 6 months prior to screening.
• •Myocardial infarction within 6 months prior to screening.
• •History of documented congestive heart failure (New York Heart Association functional classification III-IV).
• •Uncontrolled hypertension defined by a Systolic Blood Pressure ≥ 160 mmHg and/or Diastolic Blood Pressure ≥ 100 mmHg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication (s) was allowed prior to screening.
• •Ventricular arrhythmias.
• •Supraventricular and nodal arrhythmias not controlled with medication.
• •Other cardiac arrhythmia not controlled with medication.
• •Corrected QT (QTcF) \> 470 ms using Fridericia's correction on the screening electrocardiogram (ECG) (as mean of triplicate ECGs).
• •Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mmHg, with or without anti-hypertensive medication.
• •Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).
• •Other Protocol defined Inclusion/Exclusion may applied.