- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02050815
MEK162 in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function (MEK162)
A Phase I, Multicenter, Open-label, Single-dose Study to Assess the Pharmacokinetics of MEK162 in Subjects With Mild, Moderate and Severe Hepatic Impairment
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Colorado
-
Lakewood, Colorado, United States, 80228
- DaVita Clinical Research-Denver
-
-
Florida
-
Miami, Florida, United States, 33014
- Clinical Pharmacology of Miami (CPMI)
-
Orlando, Florida, United States, 32809
- Orlando Clinical Research Center
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55404
- Davita Clinical Research
-
-
Missouri
-
Kansas City, Missouri, United States, 64131
- Kansas City Research Institute, LLC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MEK162
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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
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
|
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
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
|
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
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
|
pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relationship between PK parameters versus hepatic function laboratory parameters
Time Frame: Screening, Baseline, Day 2, Day 6 (Day of discharge)
|
To explore the relationship between hepatic liver function and PK.
Pharmacokinetic parameters will be correlated to hepatic lab parameters.
|
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)
|
Adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) grade (severity) and frequency, and other safety data
|
Screening, Baseline, Day 2, Day 6 (Day of discharge)
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CMEK162A2104
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hepatic Impairment
-
PfizerRecruitingHealthy Volunteers | Moderate Hepatic Impairment | Severe Hepatic ImpairmentUnited States
-
GlycoMimetics IncorporatedCompletedModerate Hepatic Impairment | Normal Hepatic FunctionUnited States
-
Astellas Pharma Europe B.V.Medivation, Inc.CompletedSevere Hepatic Impairment | Normal Hepatic FunctionBulgaria
-
Agios Pharmaceuticals, Inc.CompletedModerate Hepatic ImpairmentUnited States
-
Merck Sharp & Dohme LLCCompletedModerate Hepatic ImpairmentUnited States
-
EQRx International, Inc.CompletedSevere Hepatic ImpairmentUnited States
-
PfizerCompleted
-
TakedaCompletedSevere Hepatic ImpairmentUnited States
-
Bausch Health Americas, Inc.TerminatedSevere Hepatic ImpairmentUnited States
-
ShireCompleted
Clinical Trials on MEK162
-
PfizerCompletedBRAF or NRAS Mutant Metastatic MelanomaUnited States, Netherlands, Italy, Germany, Switzerland
-
Array Biopharma, now a wholly owned subsidiary...CompletedAdvanced Solid TumorJapan
-
Array Biopharma, now a wholly owned subsidiary...WithdrawnCardiomegalyUnited States, United Kingdom
-
PfizerCompletedSolid Tumor and Hematologic MalignanciesUnited States
-
PfizerCompletedLocally Advanced or Metastatic NRAS Mutant MelanomaUnited States, Australia, Germany, Italy, Netherlands
-
Array Biopharma, now a wholly owned subsidiary...CompletedAdvanced Solid Tumors | Selected Solid TumorsUnited States, Germany, Canada, Spain, Netherlands, Singapore, Switzerland
-
Array Biopharma, now a wholly owned subsidiary...CompletedAdvanced Solid TumorsUnited States, Spain, Canada, Norway, Switzerland
-
Array BioPharmaCompletedAML | Advanced and Selected Solid Tumors | High Risk and Very High Risk MDSUnited States, Australia, Italy, Spain, France, Switzerland, United Kingdom
-
Array Biopharma, now a wholly owned subsidiary...TerminatedUveal MelanomaUnited States, France, Germany, Netherlands, Spain, United Kingdom
-
PfizerCompletedSolid Tumors Harboring a BRAF V600 MutationUnited States, France, Italy, Singapore, Australia, Spain, Switzerland, Canada, Belgium