To Assess the Enzyme Inducing Effects of Carbamazepine on the PK of Mirdametinib in Healthy Participants

NCT07279233 | Completed Phase 1 FDA Drug

• 1 other identifier: MEK-NF1-105
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effect of carbamazepine on the blood levels of mirdametinib and how long it takes the body to eliminate mirdametinib when both drugs are administered orally in healthy participants. The study may last up to approximately 64 days for each participant.

Conditions

Healthy; Volunteer

Keywords

Drug interaction; Mirdametinib; Carbamazepine

Outcome Measures

Primary Outcomes (3)

• The geometric mean ratio of mirdametinib plasma area under the concentration-time curve from dosing extrapolated to infinity (AUCinf) of Mirdametinib

  Day 1 to Day 29

• The geometric mean ratio area under the concentration-time curve from dosing to time of last quantifiable concentration (AUClast) of Mirdametinib

  Day 1 to Day 29

• The geometric mean ratio of maximum observed concentration (Cmax) of Mirdametinib

  Day 1 to Day 22

Secondary Outcomes (11)

• Number of participants who Experience an Adverse Event

  Up to a maximum of 36 days

• AUCinf of Metabolites M15, M22, and M30

  Day 1 to Day 29

• AUClast of Metabolites M15, M22, and M30

  Day 1 to Day 29

• Cmax of Metabolites M15, M22, and M30

  Day 1 to Day 22

• Time of maximum observed concentration (Tmax) of Mirdametinib and Metabolites M15, M22, and M30

  Day 1 to Day 22

Study Arms (2)

Period 1 Mirdametinib

ACTIVE COMPARATOR

Mirdametinib 6-mg single dose given orally alone on Day 1 as three 2-mg capsules following a 10-hour fast.

Drug: Mirdametinib

Period 2 Mirdametinib and carbamazepine

EXPERIMENTAL

Mirdametinib 6-mg single dose given orally on Day 22 in Period 2 as three 2-mg capsules following a 10-hour fast in combination with carbamazepine tablets that are administered orally according to the following schedule: * Days 8 and 9: 100 mg BID with meals * Days 10 and 11: 200 mg BID with meals * Days 12 through 21: 300 mg BID with meals * Day 22: 300 mg AM fasted, with mirdametinib, and 300 mg PM with meal * Days 23 through 28: 300 mg BID with meals * Days 29 through 30: no doses (observation only)

Drug: Mirdametinib and Carbamazepine

Interventions

Mirdametinib DRUG

6-mg single dose given orally on Day 1

Period 1 Mirdametinib

Mirdametinib and Carbamazepine DRUG

Drug: Mirdametinib 6-mg single dose given orally on Day 22. Drug: Carbamazepine Carbamazepine extended-release (ER) (Carbamazepine ER will be given orally twice daily for 21 days with a titration schedule \[100 mg BID for 2 days, 200 mg BID for 2 days, and then 300 mg BID\]).

Period 2 Mirdametinib and carbamazepine

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 must sign the informed consent form (ICF) prior to any study-related procedures being performed.
• Participant is male or female and between 18 and 65 years of age (inclusive) at the time of informed consent.
• Participant has a body mass index (BMI) ≥18 and ≤32 kg/m² (inclusive) at Screening and Day -1.
• Participant is in good health in the judgment 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, hematology, coagulation, and urinalysis tests carried out at Screening and Day -1. Clinical laboratory test results within normal reference range for the population or investigative site, or results within acceptable deviations that are judged to be not clinically significant by the investigator.
• Note: Laboratory values that are out-of-range may be confirmed by a single repeat per investigator discretion.
• Participant has normal or mildly impaired renal function as estimated by the Chronic Kidney Disease Epidemiology Collaboration formula (i.e., ≥60 mL/min).
• 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 should also be used by the female partner if she is of childbearing potential.
• Female participants that are not pregnant or breastfeeding, and for whom one of the following conditions applies:
• Is a woman of non-childbearing potential.
• Is a WOCBP and agrees to use an acceptable contraceptive method from the time of signed informed consent and for at least 6 weeks after the last dose of study medication; AND
• 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 2019 \[COVID-19\] 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 HIV at Screening, they are not eligible for participation in the study.
• \. Participant has a history of any neurological conditions including movement disorders and seizures.
• \. Participant has a history of stomach or GI surgery or resection that would potentially alter absorption, metabolism, and/or excretion of PO administered drugs (exceptions include participants who underwent appendectomy or any type of hernia repair).
• \. Participant has a history of pre-existing condition interfering with normal GI anatomy or motility and potentially alter the absorption, metabolism, and/or excretion of orally administered drugs.
• \. Participants with 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 (PSA), 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 enrollment is approved by both the investigator and the sponsor's medical monitor.
• \. Participant has any evidence of glaucoma or retinal vein occlusion, visual blurring or uncorrected vision issues, or intraocular pressure (IOP) \>21 mmHg on Day -1.
• \. Participant has 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
• Heart rate \<45 or \>100 bpm after 5 minutes of rest
• Abnormal QT interval corrected by Fridericia's formula (QTcF) interval (≥450 msec) or ECG abnormalities interfering with QT/QTc interpretation
• Risk factors for torsades de pointes
• Ejection fraction \<55% 10. Participant has an acute illness, significant infection, or incomplete bladder emptying (voiding \>2 times/night).

Sponsors & Collaborators

• SpringWorks Therapeutics, Inc.: lead

Study Sites (1)

Medpace

Cincinnati, Ohio, 45227, United States

Location

MeSH Terms

Interventions

mirdametinib; Carbamazepine

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

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

Model Details: Fixed-sequence

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: December 12, 2025
• Study Start: December 15, 2025
• Primary Completion: February 27, 2026
• Study Completion: February 27, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)