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

Inclusion Criteria

• The participant is able to provide written informed consent.
• Healthy male or non-pregnant, non-lactating female participants aged 18 to 55 years, inclusive, with a BMI of 18 kg/m2 or greater, but less than 30 kg/m2. The participant is considered by the investigator to be in good general health status as determined by physical examination, vital signs, temperature, medical history, no clinically significant abnormalities at investigator's discretion in laboratory and urine analyses, and with normal organ function as defined below:
• Normal renal function: creatinine clearance ≥ 90 mL/min.
• Normal liver enzymes and bilirubin (≤ ULN).
• ECG, with QTcF interval ≤ 450 msec; at screening.
• Healthy female participants must be:
• Documented to be surgically sterile (surgical methods inclusive of hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) or postmenopausal (amenorrhea for ≥24 months without an alternative medical cause and FSH ≥30 mIU/mL).

OR

• Using contraception, including 1 highly effective nonhormonal methods (eg, intrauterine device) in combination with a barrier contraception (eg, male or female condoms, diaphragm, spermicide, etc.) from start of plixorafenib administration until 30 days after the last plixorafenib administration, and having a negative serum or urine β-hCG pregnancy test (with a sensitivity of at least 25 mIU/mL) at screening and check in.
• Male participants with female partners of childbearing potential must be sterile (confirmed by documented azoospermia 90 days after the procedure) or agree to use (from check-in until 90 days after discharge) one of the following approved methods of contraception: male condom with spermicide; sterile sexual partner (males must still agree to use condom with their surgically sterile female partner if unable to provide documentation of partner's sterility); or practice abstinence (abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the participant, periodic abstinence won't be allowed); or use of an intrauterine device with spermicide by female sexual partner; a female condom with spermicide; a contraceptive sponge with spermicide; an intravaginal system; a diaphragm with spermicide; a cervical cap with spermicide; or oral, implantable, transdermal, or injectable contraceptives.
• Male participants must refrain from sperm donation and female participants must refrain from egg donation from check-in until 90 days after discharge from the study.
• The participant agrees to comply with all protocol requirements for the duration of the study.

Exclusion Criteria

• The participant has a history of clinically significant drug allergy or anaphylaxis, including known hypersensitivity to any components of plixorafenib or cobicistat.
• The participant has a history of any condition(s) or gastrointestinal surgeries, including gallbladder procedures, which might affect drug absorption, metabolism, or excretion.
• 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.
• 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.
• 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.
• 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 un