Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEK162 in Noonan Syndrome Hypertrophic Cardiomyopathy

NCT01556568 | Withdrawn Phase 2

• 2 other identifiers: CMEK162Y22012011-003392-10
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of the study is to determine whether the ability of MEK162 to antagonize MEK activation in NS HCM patients, who usually have upstream mutations in the Ras-Raf-Mek-Erk pathway that lead to MEK activation, would be beneficial over a 6 month treatment period in hypertrophy regression.

Conditions

Cardiomegaly

Keywords

Noonan Syndrome, hypertrophic cardiomyopathy.

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Left ventricular mass (LVM)

  Change in LVM after 3 months and 6 months of treatment using magnetic resonance imaging.

  Baseline to 3 months and 6 months

Secondary Outcomes (15)

• Change from baseline in Cardiac energetics state at 3 months and 6 months

  Baseline to 3 months and 6 months

• Number of patients with adverse events, serious adverse events and death

  6 months

• Pharmacokinetics of MEK162 and metabolite (AR00426032): The trough plasma concentration (Ctrough) just prior to drug administration

  Days 1, 8, 15, 28, 56, 84, 140 and 182

• Pharmacokinetics of MEK162 and metabolite (AR00426032): maximum drug exposure of MEK162 and its metabolite (AR00426032) in plasma

  Day 1 and Day 8

• Pharmacokinetics of MEK162 and metabolite (AR00426032): time to reach peak concentration (Tmax) in plasma

  Day 1 and Day 8

Study Arms (1)

MEK162

EXPERIMENTAL

Patients will be treated with MEK162 only and will be uptitrated or down titrated based on safety and tolerability observed.

Drug: MEK162

Interventions

MEK162 DRUG

MEK162

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female Noonan syndrome patients with confirmed cardiac hypertrophy, age 18 to 65 years of age included, and in general good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
• Cardiac hypertrophy is defined by left ventricular wall thickness greater than or equal to 12 mm by echocardiography or MRI, or the change in wall thickness is accompanied by an associated increase in left ventricular mass which is defined by echo or MRI as greater than 134 g/m2 and 110 g/m2 in men and women, respectively.
• Subjects must weigh at least 45 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 34 kg/m2.

You may not qualify if:

• Primary Long QT syndrome or a history of significant ECG abnormalities judged by the investigators to be inappropriate for participation in the current study.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
• Sexually active males must use a condom during intercourse while taking the drug during treatment, for 5 half lives after stopping treatment and should not father a child in this period.
• Use of any prescription drugs other than beta-blockers, diuretics, CCB, amiodarone, disopyramide, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing. If needed, (i.e. an incidental and limited need) paracetamol or acetaminophen is acceptable, but must be documented in the Concomitant medications/Significant non-drug therapies page of the eCRF.

Sponsors & Collaborators

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

Study Sites (2)

Pfizer Investigative Site

Boston, Massachusetts, 02115, United States

Location

Pfizer Investigative Site

London, W1G 8PH, United Kingdom

Location

MeSH Terms

Conditions

Cardiomegaly; Noonan Syndrome; Cardiomyopathy, Hypertrophic

Interventions

binimetinib

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Cardiomyopathies; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2012
• First Posted: March 16, 2012
• Study Start: February 1, 2012
• Primary Completion: May 1, 2017
• Last Updated: October 6, 2020

Record last verified: 2020-10

Locations

US (1); GB (1)