E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-obstructive hypertrophic cardiomyopathy |
miocardiopatía hipertrófica no obstructiva |
|
E.1.1.1 | Medical condition in easily understood language |
non-obstructive hypertrophic cardiomyopathy, a genetic condition that affects the heart |
miocardiopatía hipertrófica no obstructiva, una afección genética que afecta el corazón. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020871 |
E.1.2 | Term | Hypertrophic cardiomyopathy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of LCZ696 on cardiopulmonary exercise test (CPET) parameters in patients with non-obstructive HCM |
Evaluar la eficacia de LCZ696 en los parámetros de la prueba de esfuerzo cardiopulmonar (PECP) en pacientes con MCH no obstructiva |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of LCZ696 in patients with non-obstructive HCM |
Evaluar la seguridad y tolerabilidad de LCZ696 en pacientes con MCH no obstructiva |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosed with Hypertrophic Cardiomyopathy with a left ventricular wall thickness greater than or equal to 13mm as determined by the echocardiogram obtained during the screening/baseline period • Left ventricular ejection fraction (LVEF) greater than or equal to 50% as determined by echocardiogram obtained during the screening/baseline period • Symptoms consistent with New York Heart Association (NYHA) Class II-III heart failure by physician assessment, or asymptomatic/NYHA Class I patients with: o NT-proBNP blood sample levels above 250 pg/ml and o peak VO2 of <80% of predicted based on age and gender as determined by cardiopulmonary exercise testing |
• Diagnóstico de miocardiopatía hipertrófica (ventrículo izquierdo hipertrofiado y no dilatado sin causa sistémica aparente) con un grosor de la pared ventricular izquierda de >/= 13 mm mediante el ecocardiograma obtenido durante el periodo de selección/basal • Fracción de Eyección del Ventriculo Izquierdo (FEVI) del >/=50 % en el ecocardiograma obtenido durante el periodo de selección/basal. • Síntomas compatibles con una insuficiencia cardíaca de clase II-III de la New York Heart Association (NYHA) en la evaluación del médico, o pacientes asintomáticos/clase I de la NYHA con: oNT-proBNP por encima de 250 pg/ml y o VO2 pico <80 % del valor teórico según la edad y el sexo. |
|
E.4 | Principal exclusion criteria |
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for ≥7 days after stopping study drug • Patients with a resting or provokable left ventricular outflow tract gradient of greater than or equal to 30mm Hg • Septal reduction procedure within 3 months of the screening/baseline visit • History of atrial fibrillation or placement of ICD for secondary prevention • Patients with a peak VO2 on the screening/baseline cardiopulmonary exercise test of >80% of predicted based on age and gender • Patients who require treatment with ACE inhibitors, angiotensin receptor blockers (ARBs), or renin inhibitors • Known infiltrative or storage disorder such as Fabry disease, or amyloidosis • Known or suspected symptomatic coronary artery diseases or evidence of prior myocardial infarction • Systolic blood pressure of <100 mmHg or symptomatic hypotension during the screening/baseline period or treatment run-in period • Contraindication to ARB administration or prior history of angioedema • Persistent uncontrolled hypertension Other protocol-defined inclusion/exclusion criteria may apply |
• Mujeres en edad fértil, definidas como todas las mujeres fisiológicamente capaces de quedar embarazadas, a menos que estén utilizando métodos anticonceptivos altamente efectivos durante la dosificación y durante >/=7 días después de suspender el fármaco del estudio. • Pacientes con un gradiente del tracto de salida del ventrículo izquierdo en reposo o provocable >30 mmHg • Procedimiento de reducción septal durante los 3 meses anteriores a la visita de selección/basal. • Antecedentes de fibrilación auricular o colocación de ICD para prevención secundaria. •Pacientes con un VO2 pico en la prueba de esfuerzo cardiopulmonar de la selección/basal >80 % del valor teórico según la edad y el sexo. • Pacientes que necesiten tratamiento con inhibidores de la ECA, antagonistas de los receptores de la angiotensina (ARAII) o inhibidores de la renina. • Trastorno infiltrativo o por depósito como enfermedad de Fabry, o amiloidosis • Enfermedades coronarias sintomáticas conocidas o sospechadas o evidencia de infarto de miocardio previo • Presión arterial sistólica <100 mmHg o hipotensión sintomática durante el periodo de selección/basal o el periodo de tratamiento de preinclusión. •Contraindicación a la administración de ARAII, o antecedentes de angioedema. •Hipertensión no controlada persistente Se pueden aplicar otros criterios de inclusión / exclusión definidos por el protocolo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in peak VO2 as measured by cardiopulmonary exercise test (CPET) |
Cambio desde el valor basal en el VO2 máximo medido por la prueba de ejercicio cardiopulmonar (CPET) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to 50 weeks |
Basal a 50 semanas |
|
E.5.2 | Secondary end point(s) |
Adverse events (AEs), vital signs, ECGs, physical examinations and safety labs |
Efectos adversos (AE), signos vitales, ECG, exámenes físicos y laboratorios de seguridad. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Over numerous visits until end of study |
Durante numerosas visitas hasta el final del estudio |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability |
Tolerabilidad |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Finland |
Germany |
Greece |
Korea, Republic of |
Spain |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Study completion is defined as when the last patient finishes their EOS/Study Completion visit and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision. |
La finalización del estudio se define cuando el último paciente finaliza su visita EOS / Finalización del estudio y cualquier evaluación repetida asociada con esta visita ha sido documentada y seguida adecuadamente por el investigador o, en el caso de una decisión de finalización temprana del estudio, la fecha de esa decisión. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 13 |