Hepatic ImpairmentPhase 1MEK162NCT02050815
MEK162 in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function
A Phase 1 study testing MEK162 in people with Hepatic Impairment, run by Array Biopharma, now a wholly owned subsidiary of Pfizer at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- MEK162
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2014to 26 Aug 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- Additional inclusion criteria for subjects with abnormal liver function determined by elevation of serum total bilirubin are:
- Absolute neutrophil count (ANC) > 1000 cell/mm3
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- 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
Who cannot join
- 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
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- 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
- Consumption of alcohol within 3 days prior to dosing or during the study
- Additional exclusion criteria for subjects with normal hepatic function:
- Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as ALT, AST, GGT, alkaline phosphatase, or serum bilirubin. ALT and AST beyond the normal range before inclusion Presence of impaired renal function as indicated by abnormal creatinine (creatinine clearance < 80 mL/min) values and/or serum creatinine ≥1.8 mg/dL- A positive Hepatitis B or Hepatitis C test result
- Additional exclusion criteria for subjects with elevation of serum bilirubin > UNL:
- Symptoms or history of encephalopathy (Grade II or worse) within 4 weeks of study entry
- Clinical evidence of severe ascites requiring intervention
- International normalized ratio (INR) >2.5
- Any evidence of progressive liver disease within the last 3 weeks prior to the screening visit) as indicated by worsening of clinical manifestations (i.e.: ascites, encephalopathy) and/or laboratories abnormalities (liver transaminases, alkaline phosphatase and GGT or a ≥ 50% worsening of serum bilirubin or prothrombin time)
- History of surgical portosystemic shunt with complications (i.e. hepatic encephalopathy, heart failure)
- Active bleeding during the last 28 days prior to dosing including variceal bleeding
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Kansas City Research Institute, LLC
Kansas City, Missouri, 64131
DaVita Clinical Research-Denver
Lakewood, Colorado, 80228
Clinical Pharmacology of Miami (CPMI)
Miami, Florida, 33014
DaVita Clinical Research
Minneapolis, Minnesota, 55404
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
Official title: A Phase I, Multicenter, Open-label, Single-dose Study to Assess the Pharmacokinetics of MEK162 in Subjects With Mild, Moderate and Severe Hepatic Impairment
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
- Being tested
- MEK162
- Keywords
- MEK162, Hepatic impairment, Healthy subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEK162Drug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: MEK162 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
To explore the relationship between hepatic liver function and PK. Pharmacokinetic parameters will be correlated to hepatic lab parameters.
Measured: Screening, Baseline, Day 2, Day 6 (Day of discharge)
Number of subjects with adverse events as a measure of safety and tolerability
Adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) grade (severity) and frequency, and other safety data
Measured: Screening, Baseline, Day 2, Day 6 (Day of discharge)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2014 (estimated)
- Study startMar 2014
- Primary completion1 Aug 2016
- Study completion26 Aug 2016
Why it stopped: The Sponsor is terminating the study because the primary objective was achieved after 5 of the 6 subjects were assessed in the final cohort.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Array Biopharma, now a wholly owned subsidiary of Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02050815
- Sponsor's protocol ID
- CMEK162A2104
- Acronym
- MEK162
- Status last verified
- Sep 2020
- First submitted
- 16 Jan 2014
- Last updated
- 17 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 40549341
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multicenter, Open-label, Single-dose Study to Assess the Pharmacokinetics of MEK162 in Subjects With Mild, Moderate and Severe Hepatic Impairment
- ClinicalTrials.gov ID
- NCT02050815
- Acronym / sponsor ID
- MEK162 / CMEK162A2104
- Conditions
- Hepatic Impairment
- Keywords
- MEK162, Hepatic impairment, Healthy subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor is terminating the study because the primary objective was achieved after 5 of the 6 subjects were assessed in the final cohort.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Array Biopharma, now a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
- Study start
- Mar 2014
- Primary completion
- 1 Aug 2016 (actual)
- Study completion
- 26 Aug 2016 (actual)
- First posted
- 31 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MEK162 | Experimental | Drug: MEK162A 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
- Additional inclusion criteria for subjects with abnormal liver function determined by elevation of serum total bilirubin are:
Key exclusion criteria (25 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEK162 | Drug | MEK162 |
Primary outcome
PK parameters assessed by Tmax
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120
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
PK parameters assessed by Cmax
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120
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
PK parameters assessed by AUCinf
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120
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
PK parameters assessed by AUC0last
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120
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
2 secondary outcomes
Relationship between PK parameters versus hepatic function laboratory parameters
Time frame: Screening, Baseline, Day 2, Day 6 (Day of discharge)
Number of subjects with adverse events as a measure of safety and tolerability
Time frame: Screening, Baseline, Day 2, Day 6 (Day of discharge)
Results and safety
The study was stopped early (reason given: The Sponsor is terminating the study because the primary objective was achieved after 5 of the 6 subjects were assessed in the final cohort.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2020.
- Derived from this study: PubMed 40549341Piscitelli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MEK162 in people with Hepatic Impairment, run by Array Biopharma, now a wholly owned subsidiary of Pfizer at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The Sponsor is terminating the study because the primary objective was achieved after 5 of the 6 subjects were assessed in the final cohort.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK parameters assessed by Tmax (time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02050815, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2020.