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

NCT07840612 | Not Yet Recruiting Phase 1

• 2 other identifiers: MEK-NF1-1062026-526403-30-00
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-centre, open-label, fixed-sequence, 2-period study in healthy participants. The total study duration for each participant will be up to approximately 56 days, including a 28-day screening period, a 19-day assessment period (including Period 1 and Period 2), and a follow-up (FU) visit approximately 7 days after clinical research unit (CRU) discharge.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Geometric Mean Ratios of Mirdametinib Pharmacokinetic Plasma Concentration in Presence and Absence of Probenecid

  Day 1 up to Day 26

Secondary Outcomes (4)

• Number of Participants with Adverse Events (AEs)

  Screening up to Day 26

• Number of Participants with Clinically Significant Findings in Clinical Laboratory Tests, 12-lead Electrocardiograms (ECGs), Vital Signs, Ophthalmic and Physical Examinations

  Screening up to Day 26

• Pharmacokinetic Plasma Concentration of Mirdametinib Alone and Following Probenecid

  Day 1 up to Day 26

• Pharmacokinetic Plasma Concentration of Mirdametinib Metabolites Alone and Following Probenecid

  Day 1 up to Day 26

Study Arms (2)

Mirdametinib

EXPERIMENTAL

Drug: Mirdametinib

Mirdametinib and Probenecid

EXPERIMENTAL

Drug: Mirdametinib; Drug: Probenecid

Interventions

Mirdametinib DRUG

Mirdametinib capsules administered orally.

Mirdametinib; Mirdametinib and Probenecid

Probenecid DRUG

Probenecid tablets administered orally.

Mirdametinib and Probenecid

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Research Site

Darmstadt, Germany

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Interventions

mirdametinib; Probenecid

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Central Study Contacts

Communication Center

CONTACT

+49 6151 72 5200; service@emdgroup.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2026
• First Posted: September 25, 2026
• Study Start: September 25, 2026
• Primary Completion (Estimated): November 17, 2026
• Study Completion (Estimated): November 17, 2026
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)