A study to look at the effect of the study drug on heart muscle thickness, the amount of drug that ends up in the blood, and the safety and tolerability of study drug in Noonan syndrome patients.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2011-003392-10-GB
• Date of registration: 24/08/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A study to look at the effect of the study drug on heart muscle thickness, the amount of drug that ends up in the blood, and the safety and tolerability of study drug in Noonan syndrome patients.
• Scientific title: An open label study to assess safety, tolerability, pharmacokinetics and pharmacodynamics of MEK162 in Noonan syndrome hypertrophic cardiomyopathy.
• Date of first enrolment: 23/01/2012
• Target sample size: 22
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003392-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceuticals UK Ltd

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceuticals UK Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- 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, unless using highly effective contraception during the study and for 5 half lives after stopping treatment - 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 Other protocol-defined inclusion/exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Noonan syndrome hypertrophic cardiomyopathy
MedDRA version: 14.1 Level: PT Classification code 10029748 Term: Noonan syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 14.1 Level: PT Classification code 10020871 Term: Hypertrophic cardiomyopathy System Organ Class: 10007541 - Cardiac disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Code: MEK162
Pharmaceutical Form: Film-coated tablet
CAS Number: 606143-89-9
Current Sponsor code: MEK162
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Main Objective: To assess the effect of MEK162 when administered b.i.d. for 6 months, on cardiac hypertrophy in Noonan syndrome patients with confirmed hypertrophic cardiomyopathy

Primary end point(s): Left ventricular mass and left ventricular mass index

Secondary Objective: - To evaluate the safety and tolerability of MEK162 when administered b.i.d. for 6 months in Noonan syndrome patients with confirmed hypertrophic cardiomyopathy - To evaluate the pharmacokinetics of MEK162 and metabolite (AR00426032) following multiple dose administration in the target population - To assess the effect of MEK162 on cardiac energetic improvement assessed by P-31 magnetic resonance spectroscopy (MRS) in this population following 3 and 6 months of treatment. - To assess the effect of MEK162 on cardiac function and hemodynamics after 3 and 6 months of treatment

Timepoint(s) of evaluation of this end point: 6 months of treatment

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 6 months of treatment for the three secondary end points

Secondary end point(s): - PCr/ATP ratio - Safety (vital signs, ECG, blood tests, adverse events) - Pharmacokinetics

Secondary ID(s)

CMEK162Y2201

Source(s) of Monetary Support

Novartis Pharma Services AG