MEK162 in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function

NCT02050815 | Terminated Phase 1

• 1 other identifier: CMEK162A2104
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a phase I, multi-center, open-label, single oral dose, parallel group study to assess the PK and safety of MEK162 in subjects with impaired hepatic function and healthy subjects with normal hepatic function. Subjects will be assigned by hepatic function defined by elevation of serum total bilirubin and serum AST as determined at the screening and baseline visits. The study population will be healthy male and postmenopausal or sterile female subjects who meet all of the inclusion and none of the exclusion criteria. A minimum of 24 evaluable subjects (6 subjects per group) will be enrolled. The groups are: Group 1-healthy volunteers, Group 2-Mild hepatic impairment, Group 3-Moderate hepatic impairment and Group 4-Severe hepatic impairment. Once approved for enrollment, participants will be confined to the facility for 5 days, given a single dose of MEK162 and monitored for safety assessments, labs and PK will be assessed.

Conditions

Hepatic Impairment

Keywords

MEK162; Hepatic impairment; Healthy subjects

Outcome Measures

Primary Outcomes (4)

• PK parameters assessed by Tmax

  Blood pharmacokinetic samples will be collects at various timepoints to assess the MEK162 concentration levels. MEK162 concentrations and preliminary PK parameters will be analyzed in the two groups to determine if a dose adjustment is required in patients with moderate hepatic impairment

  pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120

• PK parameters assessed by Cmax

  Blood pharmacokinetic samples will be collects at various timepoints to assess the MEK162 concentration levels. MEK162 concentrations and preliminary PK parameters will be analyzed in the two groups to determine if a dose adjustment is required in patients with moderate hepatic impairment

  pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120

• PK parameters assessed by AUCinf

  Blood pharmacokinetic samples will be collects at various timepoints to assess the MEK162 concentration levels. MEK162 concentrations and preliminary PK parameters will be analyzed in the two groups to determine if a dose adjustment is required in patients with moderate hepatic impairment

  pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120

• PK parameters assessed by AUC0last

  Blood pharmacokinetic samples will be collects at various timepoints to assess the MEK162 concentration levels. MEK162 concentrations and preliminary PK parameters will be analyzed in the two groups to determine if a dose adjustment is required in patients with moderate hepatic impairment

  pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120

Secondary Outcomes (2)

• Relationship between PK parameters versus hepatic function laboratory parameters

  Screening, Baseline, Day 2, Day 6 (Day of discharge)

• Number of subjects with adverse events as a measure of safety and tolerability

  Screening, Baseline, Day 2, Day 6 (Day of discharge)

Study Arms (1)

MEK162

EXPERIMENTAL

A minimum of 24 subjects (6 subjects per group) will be enrolled. Enrollment into Group 1 (control group with normal hepatic function) should be similar to the enrollment into Group 2, 3 and 4 with respect to age, gender, and body weight. Enrollment into Group 1 will remain open until the enrollment into the mild, moderate, and severe impairment groups are complete with matching controls for comparison. Serum level of total bilirubin and AST will be used to determine which group the hepatic impaired patient will be allocated l. Dosing of the different treatment groups will be staggered. Initially, 6 subjects in Group 1 (normal hepatic function) and 6 subjects in Group 2 will receive a single oral dose of MEK162 on Day 1.

Drug: MEK162

Interventions

MEK162 DRUG

MEK162

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to any screening procedures
• Male or female (postmenopausal or sterilized)
• Subject body weight at least 45 kg and a body mass index (BMI) in the range of 18 to 35.0 kg/m2
• Subjects with normal hepatic function must have total bilirubin ≤ upper limit of normal (≤ ULN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) ≤ ULN, serum creatinine ≤ ULN, serum amylase and lipase ≤ ULN
• Absolute neutrophil count (ANC) \> 1000 cell/mm3
• Hb \> 9 mg/dl,
• Platelet count \> 30,000/mm3
• Serum creatinine ≤ 1.8 mg/dl
• Otherwise considered healthy and free of significant medical disorders unrelated to the subject's hepatic disorder

You may not qualify if:

• Women of child-bearing potential
• Pregnant or nursing (lactating) women
• Subjects with impaired cardiovascular function or clinically significant cardiovascular diseases
• Uncontrolled arterial hypertension despite medical treatment
• History or current evidence of retinal vein occlusion (RVO) or current risk factors of RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes),
• History of Gilbert's syndrome
• Immuno-compromised subjects (including known history/seropositivity of HIV)
• Any surgical or medical condition (other than hepatic impairment) or receiving any pharmacological treatment which might significantly alter the absorption or metabolism of drugs or which may jeopardize the subject in case of participation in the study
• Antecedent of malignancy with the following exceptions: adequately treated basal cell or squamous cell carcinoma of the skin
• Subjects who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• Subjects who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
• History of clinically significant drug allergy
• Prior therapy with a MEK-inhibitor
• Use of an investigational drug within 30 days of screening
• Current smoker or has used tobacco products or products containing nicotine within 7 days prior to dosing of study drug

Sponsors & Collaborators

• Array Biopharma, now a wholly owned subsidiary of Pfizer: lead

Study Sites (5)

DaVita Clinical Research-Denver

Lakewood, Colorado, 80228, United States

Location

Clinical Pharmacology of Miami (CPMI)

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Kansas City Research Institute, LLC

Kansas City, Missouri, 64131, United States

Location

Related Publications (1)

• Piscitelli J, Hahn E, Wollenberg L, Chavira R, Del Frari L, Reddy MB. Pharmacokinetics of Binimetinib in Participants with Hepatic Impairment. Clin Pharmacokinet. 2025 Aug;64(8):1217-1230. doi: 10.1007/s40262-025-01509-0. Epub 2025 Jun 23.

  PMID: 40549341 DERIVED

MeSH Terms

Interventions

binimetinib

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2014
• First Posted: January 31, 2014
• Study Start: March 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 26, 2016
• Last Updated: September 17, 2020

Record last verified: 2020-09

Locations

US (5)