A Study to Assess the Effects of Probenecid on the Pharmacokinetics of Mirdametinib and Its Metabolites in Healthy Participants

Inclusion criteria

• Participant has a body mass index greater than or equal to (>=) 18 and less than or equal to (<=) 30 kilograms per meter square (kg/m^²) (inclusive) at Screening.
• Participant is in good health in the judgement of the investigator on the basis of a medical evaluation performed at Screening, Day -1, and predose on Day 1, and the results of clinical chemistry, haematology, and urinalysis tests carried out at Screening and Day -1.
• Participant has alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels less than (<) 1.5*the upper limit of normal (ULN) at Screening.
• Participant has normal renal function as defined in the protocol.
• Participant must have no clinically significant values outside the normal reference range of laboratory parameters for creatine phosphokinase (CPK), alkaline phosphatase (ALP), as well as leukocytes, neutrophils, and hemoglobin in the opinion of the investigator.
• Participant has sufficiently good venous access in at least 1 arm to confidently enable serial blood sampling.
• Male participants who agree to the following during study and for at least 90 days after the last dose of study medication:

• Refrain from donating or preserving sperm, PLUS either
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR
• Must agree to use a male condom when having sexual intercourse with women of childbearing potential (WOCBP). An additional form of contraception as described in the protocol should also be used by the female partner if she is of childbearing potential. Refer to protocol for definition of WOCBP.
• Female participants that are not pregnant or breastfeeding, and for whom one of the following conditions applies:

a. Is a woman of non-childbearing potential, as defined in the protocol, OR

• Is a WOCBP and agrees to use a highly effective contraceptive method as described in the protocol from the time of signed informed consent and for at least 6 months after the last dose of study medication (noting that a barrier method must be used in addition to systemically acting hormonal contraceptives); AND a. All female participants must have a negative serum pregnancy test at Screening and CRU admission (Day -1).

Exclusion criteria

• Participant has clinically significant infections (e.g., coronavirus disease [COVID] or influenza) within 90 days prior to Day 1, as judged by the investigator, or evidence of any infection within 14 days prior to Day 1. If a participant tests positive (reactive) for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at Screening, they are not eligible for participation in the study.
• Participant has a history of stomach or gastrointestinal (GI) surgery or resection that would potentially alter absorption, metabolism, and/or excretion of oral (PO) drugs (exceptions include participants who underwent appendectomy or any type of hernia repair).
• Participant has a history of a pre-existing condition interfering with normal GI anatomy or motility and potentially altering the absorption, metabolism, and/or excretion of PO drugs.
• Participant has Gilbert's syndrome.
• Participant has a history of inflammatory bowel disease, peptic ulceration, or pancreatitis within 180 days prior to Day 1.
• Participant has a history of cancer, except if judged to be in full remission for at least 5 years at the time of informed consent (except basal cell skin cancer, resected prostate cancer with an undetectable prostate-specific antigen test, undetectable cervical cancer, or squamous cell skin cancer with history of curative treatment and no recurrence for at least 3 years prior to Screening), as judged by the investigator.
• Participant has an acute illness with symptoms or treatment that has started or persisted within 14 days prior to Day 1 unless mild in severity and enrolment is approved by both the investigator and the sponsor's medical monitor.
• Participant has any evidence of glaucoma or retinal pathology at Screening or an intraocular pressure (IOP) >21 millimeters of mercury [mmHg] at Day -1.
• Participant has any cardiovascular abnormalities including:

• History of postural hypotension, unexplained syncope, or abnormal autonomic tone.
• Blood pressure <90/50 mmHg or >=140/90 mmHg after 5 minutes of rest.
• Pulse rate <50 or >90 bpm after 5 minutes of rest.
• Abnormal QT interval corrected by Fridericia's formula (QTcF) interval (>=450 milliseconds [msec]) or ECG abnormalities interfering with QT/QTc interpretation, QRS complex >=120 msec, risk factors for torsades de pointes, or any other clinically relevant abnormalities as judged by investigator.
• History of congestive heart failure.
• Ejection fraction <55%.
• Participant has an acute urinary infection or incomplete bladder emptying (voiding >2 times/night).
• Participant has substance use concerns:

• Positive alcohol, cotinine, or drug screen test.
• Consumption of an average weekly alcohol intake of >14 units/week for men or >7 units/week for women. One unit (12 grams [g]) of alcohol equals one-half pint (285 milliliters [mL]) of beer or lager, 1 glass (125 mL) of wine, or one-sixth gill (25 mL) of spirits
• Tobacco or nicotine use within 3 months prior to Screening
• Excessive consumption of xanthine-containing food or beverages (>400 milligrams per day [mg/day]).

a. Unwillingness to avoid xanthine-containing products 72 hours before dosing until after collection of the final PK sample

• Participant has taken, received, or consumed:

• Any prescription medications, over-the-counter medications, supplements, or herbal products, with exception of paracetamol/acetaminophen hormonal contraception, within 14 days or 5 half-lives if known (whichever is longer) prior to Day 1.
• Vaccines within 14 days prior to Day 1; live vaccines within 28 days prior to Day 1.
• Investigational products within 28 days or 5 half-lives (whichever is longer), or >3 new investigational entities within 12 months prior to Day 1
• Red wine, fruit or fruit juices (including, but not limited to, grapefruit, grapefruit juice, pomelos, or other exotic citrus fruits or grapefruit hybrids), or any nutrients known to modulate drug metabolising enzyme/transporters activity (including, but not limited to, cranberries or star fruits) within 72 hours of Day 1 as outlined in the protocol.
• Participant has donated blood (>450 mL) within 60 days, donated plasma within 7 days, or received blood products within 60 days prior to Screening.
• Participant is unwilling to avoid strenuous activity, sunbathing, or contact sports during the study.
• Participant has specific contraindications to the study medications:

• Known hypersensitivity to probenecid, mirdametinib, or related compounds, including ingredients.
• History of anaphylaxis or any other significant allergic reactions.
• History or presence of any clinically significant haematologic condition.
• Other contraindications including cross reactivities listed in the probenecid SmPC
• Participant is deemed unsuitable for this study in the opinion of the investigator for any additional reason.