Dose-escalation Study to Assess Selumetinib Safety, Tolerability and PK

Exclusion Criteria

• - History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer’s ability to participate in the study
• - History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• - Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• - Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the Investigator.
• - Any positive result on screening for serum hepatitis B surface antigen (HbsAg), anti hepatitis core antibody (anti HBc Ig G [and anti HBc IgM if IgG is positive], hepatitis C antibodies (anti HCV), and HIV 1 and 2 antibodies (anti HIV 1/2).
• - Abnormal vital signs, after 10 minutes supine rest.
• - Current or past history of central serous retinopathy or retinal vein thrombosis, intraocular pressure greater than 21 mmHg or uncontrolled glaucoma.
• - Known or suspected history of drug abuse, as judged by the Investigator.
• - History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
• - Positive screen for drugs of abuse or cotinine (nicotine) or positive screen for alcohol at screening or on admission to the study centre on Day -1.
• - History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to selumetinib.
• - Excessive intake of caffeine-containing drinks or food eg, coffee, tea, chocolate, Red Bull, or cola (more than 6 units of caffeine per day).
• - Use of drugs with enzyme-inducing properties such as St John’s Wort within 3 weeks prior to the first administration of IP.
• - Use of any prescribed or non prescribed medication including antacids, analgesics other than paracetamol/acetaminophen 1 g 4 times a day for occasional use, herbal remedies, vitamins, and minerals during the 2 weeks or five half-lives of the compound, whichever is longer, prior to the first administration of IP.
• - Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first admission on Day -1.Plasma donation within 1 month of screening or any blood donation/blood loss greater than 500 mL during the 3 months prior to screening.
• - Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 3 months of the first administration of IP in this study.
• - The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest. Note: volunteers consented and screened, but not randomized in this study or a previous Phase I study, are not excluded.Previous administration of study IP in the present study.- involvement in the planning and/or conduct of the study of any RPL/third party contractor or AstraZeneca employee and their close relatives regardless of their role in accordance with their internal procedures.- judged by the Investigator that the volunteer should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.-
• - Volunteers who have previously received selumetinib.
• - Volunteers who are vegans or have medical dietary restrictions.
• - Volunteers who cannot communicate reliably with the Investigator.
• - In addition, any of the following is regarded as criteria for exclusion from the genetic research: Previous bone marrow transplant, non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection