E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonsense Mutation Cystic Fibrosis |
Fibrosis quística mediada por mutación terminadora |
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E.1.1.1 | Medical condition in easily understood language |
Genetic disease characterized by difficult breathing. Other symptoms include dysfunction of the pancreas, liver, bile duct and intestine, as well as reduced fertility. |
Enfermedad genética caracterizada por dificultad para respirar. Otros síntomas son disfunción del páncreas, hígado, vías biliares e intestino, así como reducción de la fertilidad. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the ability of ataluren to improve pulmonary function relative to placebo as assessed by forced expiratory volume in 1 second (FEV1). |
Evaluar la capacidad de ataluren para mejorar la función respiratoria con respecto a placebo, evaluada mediante el FEV1. |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of ataluren on: -Pulmonary symptoms -Health-related Quality of Life (HRQL) -General well-being |
Determinar el efecto de ataluren sobre: - Síntomas respiratorios - Calidad de vida relacionada con la salud (CVRS) - Bienestar general |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. 2. Age > or = 6 years. 3. Body weight > or = 16 kg. 4. Sweat chloride >60 mEq/L. 5. Documentation of the presence of a nonsense mutation in at least 1 allele of the CFTR gene, as determined by genotyping performed at a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization. 6. Verification that a blood sample has been drawn for sequencing of the CFTR gene. 7. Ability to perform a valid, reproducible spirometry test using the study-specific spirometer with demonstration of an FEV1 ?40% and <90% of predicted for age, gender, and height. 8. Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening %-predicted FEV1 value. 9. Resting oxygen saturation (as measured by pulse oximetry) ?92% on room air. 10. Confirmed screening laboratory values within the central laboratory ranges specified in Table 2 of the protocol. 11. In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 60-day follow-up period. 12. Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions. |
1. Constancia de un documento de consentimiento/asentimiento informado firmado y fechado en el que se indique que el paciente (o su progenitor o tutor legal) ha sido informado de todos los aspectos pertinentes del ensayo. 2. Edad > o = 6 años. 3. Peso corporal >o = 16 kg. 4. Cloruro en el sudor >60 mEq/l. 5. Constancia de la presencia de una mutación terminadora en al menos un alelo del gen de CFTR, según lo determinado mediante genotipificación realizada en un laboratorio acreditado por el College of American Pathologists (CAP), o al amparo de la Clinical Laboratory Improvement Act/Amendment (CLIA), o por una organización equivalente. 6. Verificación de que se ha extraído una muestra de sangre para secuenciar el gen de CFTR. 7. Capacidad de realizar una espirometría válida y reproducible con el espirómetro específico del estudio, con demostración de un FEV1 ?40 % y< 90 % del valor teórico para la edad, sexo y estatura. 8. Demostración en la visita 2 de un porcentaje del FEV1 respecto al valor teórico válido que no difiera en más de un 15 % del valor de selección. 9. Saturación de oxígeno en reposo (medida mediante pulsioximetría) ?92 % con aire ambiente. 10. Valores analíticos de selección confirmados dentro de los intervalos del laboratorio central especificados en la tabla 2 del protocolo. 11. En pacientes que sean sexualmente activos, disposición a abstenerse de mantener relaciones sexuales o a utilizar un método anticonceptivo de barrera o médico durante la administración del fármaco del estudio y el período de seguimiento de 60 días. 12. Disposición y capacidad de cumplir las visitas programadas, el plan de administración del fármaco, los procedimientos del estudio, las pruebas analíticas y las restricciones del estudio. |
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E.4 | Principal exclusion criteria |
1. Known hypersensitivity to any of the ingredients or excipients of the study drug (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate). 2. Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF). 3. Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to screening. 4. Chronic use of inhaled aminoglycosides (eg, tobramycin) or use of inhaled aminoglycosides within 4 months prior to screening. 5. Exposure to another investigational drug within 4 weeks prior to screening. 6. Ongoing participation in any other therapeutic clinical trial. 7. Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening. 8. Treatment with intravenous antibiotics within 3 weeks prior to screening. 9. Ongoing immunosuppressive therapy (other than corticosteroids). 10. Ongoing warfarin, phenytoin, or tolbutamide therapy. 11. History of solid organ or hematological transplantation. 12. Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening. 13. Known portal hypertension. 14. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test. 15. Pregnancy or breast-feeding. 16. Current smoker or a smoking history of > or = 10 pack-years (number of cigarette packs/day × number of years smoked). 17. Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator´s opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results. |
1. Hipersensibilidad conocida a cualquiera de los componentes o excipientes del fármaco del estudio (polidextrosa, polietilenglicol 3350, poloxámero 407, manitol 25C, crospovidona XL10, hidroxietilcelulosa, vainilla, sílice coloidal o estearato de magnesio). 2. Participación previa en el ensayo de fase 3 de ataluren (PTC124-GD-009-CF). 3. Cualquier modificación (inicio, cambio de tipo de fármaco, modificación de la dosis, modificación de la pauta, interrupción, suspensión o reinicio) de un régimen crónico de tratamiento o profilaxis para la FQ o para procesos relacionados con la FQ en las 4 semanas previas a la selección. 4. Uso crónico de aminoglucósidos inhalados (por ejemplo, tobramicina) o uso de aminoglucósidos inhalados en los 4 meses previos a la selección. 5. Exposición a otro fármaco en investigación en las 4 semanas previas a la selección. 6. Participación activa en cualquier otro ensayo clínico terapéutico. 7. Constancia de una exacerbación respiratoria o infección aguda de las vías respiratorias superiores o inferiores (incluidas enfermedades víricas) en las 3 semanas previas a la selección. 8. Tratamiento con antibióticos intravenosos en las 3 semanas previas a la selección. 9. Tratamiento en curso con inmunodepresores (excepto corticoides). 10. Tratamiento en curso con warfarina, fenitoína o tolbutamida. 11. Antecedentes de trasplante de órgano sólido o hematológico. 12. Complicaciones importantes de una neumopatía (como hemoptisis masiva, neumotórax o derrame pleural) en las 8 semanas previas a la selección. 13. Hipertensión portal conocida. 14. Positividad para el antígeno de superficie del virus de la hepatitis B, anticuerpos contra el virus de la hepatitis C o el virus de la inmunodeficiencia humana (VIH). 15. Embarazo o lactancia. 16. Fumador activo o antecedentes de tabaquismo > o = 10 cajetillas-año (número de cajetillas/día x número de años de fumador). 17. Trastornos (por ejemplo, enfermedades concomitantes, alcoholismo, abuso de sustancias, trastorno psiquiátrico), antecedentes médicos, signos físicos, datos electrocardiográficos o anomalías analíticas previos o presentes que, en opinión del investigador, podrían afectar negativamente a la seguridad del paciente, hacer improbable la finalización del tratamiento o seguimiento o confundir la evaluación de los resultados del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in FEV1 as measured by spirometry |
Variación del FEV1 , determinado mediante espirometría |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, Week 1 to Week 48, 4-Week Post-Treatment follow-up |
Selección, Semana 1 a la Semana 48, seguimiento de 4 semanas post-tratamiento |
|
E.5.2 | Secondary end point(s) |
1. Rate of pulmonary exacerbations 2. Respiratory HRQL as assessed by the Cystic Fibrosis Questionnaire - Revised (CFQ-R) respiratory domain 3. Body weight and body mass index (BMI) |
1. Tasa de exacerbaciones respiratorias 2. CVRS respiratoria evaluada mediante el dominio respiratorio del cuestionario CFQ-R (Cuestionario de fibrosis quística-revisado) 3. Peso corporal e índice de masa corporal (IMC) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: Week 1 to Week 48 2: Screening, Week 1 to Week 48 3: Screening, Week 1 to Week 48, 4-Week Post-Treatment follow-up |
1: Semana 1 a la semana 48 2: Selección, semana 1 a la semana 48 3: Selección, semana 1 a la semana 48, seguimiento de 4 semanas post-tratamiento |
|
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 | Yes |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Israel |
Russian Federation |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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Last visit of the last patient excluding the long-term follow-up |
Última visita del último paciente excluyendo el seguimiento a largo plazo |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |