Effect of Hepatic Impairment on the Pharmacokinetics of Mirdametinib

NCT06997276 | Recruiting Phase 1 FDA Drug

• 1 other identifier: MEK-NF-103
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

The purposes of this study are to determine:

• The pharmacokinetics (the amount of study drug in your blood and how long it takes the body to get rid of it) of the study drug and its metabolites (substances produced as the body breaks down the study drug) in participants with moderate or severe liver function impairment compared to participants with normal liver function (also known as a healthy volunteer). Pharmacokinetics (or PK) is the study of how your body absorbs, breaks down, and removes a study drug.
• How well the study drug is tolerated and any side effects that may occur in participants with moderate or severe liver function impairment compared to participants with normal liver function. This study is for research purposes only and is not intended to treat any medical condition.

Conditions

Healthy; Hepatic Impairment

Outcome Measures

Primary Outcomes (4)

• Maximum plasma concentration (Cmax) of mirdametinib

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168-hours post dose.

• Time of maximum observed concentration (Tmax) of mirdametinib

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168-hours post dose.

• Area under the concentration-time curve from dosing extrapolated to infinity (AUC0-inf) of mirdametinib

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168-hours post dose.

• Area under the concentration-time curve from dosing to time of last quantifiable concentration (AUClast) of mirdametinib

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168-hours post dose.

Secondary Outcomes (5)

• Safety and Tolerability of mirdametinib

  Assessments: AEs at Screening up to 32 days post-dose. Clinical laboratory tests at Screening, D-1, and D8/end of treatment (ET). ECGs at Screening, D-1, or D8/ET. Vital signs at Screening, D-1, D1, and D8/ET. PEs at Screening, D-1, and Day8/ET.

• Maximum plasma concentration (Cmax) of PD-0315209

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168-hours post dose.

• Time of maximum observed concentration (Tmax) of PD-0315209

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168-hours post dose.

• Area under the concentration-time curve from dosing extrapolated to infinity (AUC0-inf) of PD-0315209

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168-hours post dose.

• Area under the concentration-time curve from dosing to time of last quantifiable concentration (AUClast) of PD-0315209

  Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168-hours post dose.

Study Arms (3)

Moderate Hepatic Impairment

OTHER

Drug: Mirdametinib (MEK Inhibitor)

Healthy Match Participants

OTHER

Drug: Mirdametinib (MEK Inhibitor)

Severe Hepatic Impairment

OTHER

Drug: Mirdametinib (MEK Inhibitor)

Interventions

Mirdametinib (MEK Inhibitor) DRUG

Mirdametinib will be administered as a single, oral, 4 mg dose in the morning on Day 1 for each study participant enrolled in the study.

Also known as: PD-0325901

Healthy Match Participants; Moderate Hepatic Impairment; Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant understands the study procedures, is willing to comply with all study requirements and restrictions and agrees to participate in the study by providing written informed consent, prior to any study-related procedures being performed.
• Participant is between 18 and 80 years of age (inclusive) at the time of informed consent.
• Participant has a body mass index (BMI) ≥18 kg/m2 and ≤32 kg/m2 (inclusive) at Screening and Day -1 and a total body weight \>50 kg.
• Male participants that agree to the following during the treatment periods and for at least 90 days after the last dose of study treatment:
• 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 Appendix 4 of the protocol should also be used by the female partner if she is of childbearing potential. Refer to Appendix 4 of the protocol for definition of WOCBP.
• Female participants that are not pregnant or breastfeeding, and for whom one of the following conditions applies:
• Refrain from donating or preserving eggs for at least 90 days after the last dose of study treatment PLUS either
• Is a woman of non-childbearing potential, as defined in Appendix 4 OR
• Is a WOCBP and agrees to use an acceptable contraceptive method as described in Appendix 4 from the time of informed consent and for at least 90 days after the last dose of study treatment; AND
• WOCBP and post-menopausal women must have a negative serum pregnancy test at Screening and on CRU admission on Day -1 unless confirmed as surgically sterile.
• Participant has sufficiently good venous access in at least one arm to confidently enable serial blood sampling.
• Participant has chronic (\>180 days), stable hepatic insufficiency, with no acute episodes of illness or liver injury within 28 days prior to Screening due to deterioration in hepatic function and must remain stable through the Screening Period.
• Aside from hepatic impairment, the participant must, in the opinion of the Investigator, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and screening laboratory evaluations.

You may not qualify if:

• Participant is deemed unsuitable for this study in the opinion of the Investigator for any additional reason, condition, or prior therapy.
• 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 with the past 14 days prior to Day 1.
• Chronic infection with Hepatitis B or C (\>180 days) may be eligible as judged by the Investigator in consultation with the Sponsor's medical monitor. If a participant tests positive for 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 PO administered drugs (exceptions include participants who underwent appendectomy, cholecystectomy, or any type of hernia repair).
• Participant has a history of pre-existing condition (apart from hepatic impairment) 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 the 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 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 symptom or treatment that has started or persisted within 14 days prior to study treatment administration unless mild in severity and enrollment is approved by both Investigator and Sponsor's medical monitor.
• Participant has a history of postural hypotension, unexplained syncope, or a Day -1 blood pressure (BP) that is less than 90 mmHg systolic or 40 mmHg diastolic.
• Participant has intraocular pressure (IOP) \>21 mmHg or any evidence of glaucoma or retinal vein occlusion at Screening or Day -1.
• Participant has a known hypersensitivity or intolerance to any of the study treatments, or excipients thereof, or a history of drug or other allergy that, in the opinion of the Investigator or Sponsor medical monitor, contraindicates their participation.
• Participant has received any P-glycoprotein or breast cancer resistance protein inhibitors within 14 days or 5 half-lives (whichever is longer) prior to Day 1. See Appendix 5 for examples of these agents.
• Participant has a history of excessive intake of alcohol, defined as an average daily intake of greater than 3 units, or an average weekly intake of greater than 14 units (one unit is equivalent to one can or bottle (250 mL) of beer, or one measure (35 mL) of spirits, or one glass (100 mL) of wine) in the last 6 months prior to Screening.
• Participant has consumed food containing poppy seeds within 72 hours of Screening and Day -1 as outlined in Section 5.3.1.
• Participant has donated blood or had a loss of more than 450 mL of blood within 60 days or donation of plasma within 7 days prior to Screening.

Sponsors & Collaborators

• SpringWorks Therapeutics, Inc.: lead

Study Sites (3)

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

RECRUITING

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

RECRUITING

American Research Corporation (Texas Liver Institute)

San Antonio, Texas, 78215, United States

RECRUITING

MeSH Terms

Interventions

mirdametinib

Central Study Contacts

US Medical Information

CONTACT

888-275-7376; eMediUSA@emdserono.com

Study Design

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

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: May 30, 2025
• Study Start: May 7, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)