A Study of the Effects of Food and Cobicistat on Plixorafenib Pharmacokinetics in Healthy Participants.

Exclusion Criteria

• •1. The participant has a history of clinically significant drug allergy or anaphylaxis, including known hypersensitivity to any components of plixorafenib or cobicistat.
• •2. The participant has a history of any condition(s) or gastrointestinal surgeries, including gallbladder procedures, which might affect drug absorption, metabolism, or excretion.
• •3. The participant has clinical evidence or a history of clinically significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurologic, or other chronic disease as judged by the investigator.
• •4. The participant has a history of psychiatric disease, a suicidal attempt, hospitalization for psychiatric disease, a period of disability due to a psychiatric disease, or administers treatment to control the condition. Psychiatric disease includes major depression, bipolar disorder, or psychosis for ≥3 months.
• •5. The participant has a history or other evidence of illness, test abnormalities, or any other conditions which would make the participant, in the opinion of the investigator, unsuitable for the study.
• •6. The participant has any history of alcoholism or drug abuse, or excessive alcohol consumption (regular alcohol intake \>21 units per week for male participants and \>14 units of alcohol per week for female participants) (1 unit is equal to approximately ½ pint \[200 mL\] of beer, 1 small glass \[100 mL\] of wine, or 1 measure \[25 mL\] of spirits) within 3 months before screening.
• •7. The participant has positive results on screen for drugs of abuse or alcohol (Section 6.2.3 \[Other analyses\]) at screening visit or Day -1.
• •8. The participant is a smoker or has used nicotine or nicotine-containing products (eg, snuff, nicotine pouch (eg ZYN), nicotine patch, nicotine chewing gum, mock cigarettes, vape cigarette alternatives, or inhalers), marijuana, and cannabinoids within 1 year before the first dose of study drug.
• •9. The participant has donated blood in the past 90 days prior to screening or has poor peripheral venous access.
• •10. The participant has a diagnosis of chronic or acute liver disease, for example, auto immune, alcoholic, or neoplastic liver disease.
• •11. The participant has positive serostatus for HIV, HCV, or HBV.
• •12. Male partners of females participants who are pregnant.
• •13. Female participant of childbearing potential who is pregnant, lactating, or planning to become pregnant within 90 days after the last dose of study drug.
• •14. The participant has received an investigational drug, biologic, or device within 3 months or 5.5 half-lives of the investigational drug (whichever is longer), before receiving study drug.
• •15. The participant has used any systemic medications, including vitamins and over the counter items, during the 14 days (or 5 times the elimination half-life of the medication, whichever is longer) before receiving study drug or will require their use during the study. Inducers and inhibitors of metabolic enzymes and/or transporters (in particular CYP3A inhibitors or inducers, P-gp, and BCRP), and herbal preparations, nutritional supplements (eg, St. John's Wort), or foods, including grapefruit juice, grapefruit/grapefruit-related citrus fruits (eg, Seville oranges, pomelos), which have been shown to produce metabolic enzyme or transporter induction or inhibition, are prohibited before 5 half-lives of the investigational drug prior to check-in (Day -1). Paracetamol ≤ 3000 mg/day will be allowed up to 2 consecutive days before dosing and during the outpatient phase of the study, as needed.
• •16. The participant has been on a diet incompatible with the on-study diet, in the opinion of the investigator or designee, within 30 days prior to the first dosing and throughout the study.
• •17. The participant is part of the clinical staff personnel or a family member of the clinical site staff.