E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cushing's disease |
Enfermedad de Cushing |
|
E.1.1.1 | Medical condition in easily understood language |
Cushing's disease |
Enfermedad de Cushing |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011651 |
E.1.2 | Term | Cushing's disease |
E.1.2 | System Organ Class | 100000004860 |
|
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 pharmacokinetics (PK) of osilodrostat in children and adolescents 6 to <18 years of age with Cushing’s Disease |
Evaluar la farmacocinética (PK) de osilodrostat en niños y adolescentes de 6 a <18 años con enfermedad de Cushing. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives include assessment of the pharmacodynamics, safety and tolerability of osilodrostat |
Los objeticos secundarios incluyen evaluar la PD, seguridad y tolerabilidad de osilodrostat |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female children and adolescents from 6 to < 18 years of age with Cushing’s disease of endogenous origin who have failed surgery or are awaiting surgery or for whom surgery is not an immediate option 2. Body weight greater 30 kg 3. Confirmed diagnosis of Cushing’s disease 4. Able to swallow study drug tablets (not crushed or split) 5. Parents or legal guardians able to provide consent/assent |
1. Niños y adolescentes de ambos sexos de 6 a <18 años con enfermedad de Cushing: en quienes la cirugía ha fracasado, que están a la espera de operarse o para quienes la cirugía no es una opción inmediata. 2. Peso Corporal mayor a 30 Kg 3. Diagnostico de Enfermedad de Cushing confirmado 4. Poder tragar comprimidos del fármaco del estudio (no machacados ni partidos). 4. Progenitores o tutores legales que puedan dar su consentimiento/asentimiento. |
|
E.4 | Principal exclusion criteria |
1. Macroadenoma complicated by compressive symptoms 2. Insufficient washout period from any other medication used to lower cortisol levels 3. Use of other investigational drugs at the time of enrollment 4. History of hypersensitivity to drugs of the same or similar chemical classes as osilodrostat 5. History of malignancy of any organ system 6. Moderate to severe renal impairment 7. Serum ALT and/or AST > 3 x ULN, or total bilirubin > 1.5 x ULN 8. History of thrombosis 9. Risk factors for QTc prolongation or Torsade de Pointes 10. Hypertensive patients with uncontrolled blood pressure 11. Patients who have undergone any major surgery within 1 month 12. Patients who have undergone trans-sphenoidal pituitary surgery within 6 weeks prior to screening, unless they have clear evidence of persistent hypercortisolemia or persistent biochemical changes consistent with Cushing’s disease 13. Use of or anticipated use of systemic glucocorticoid medications 1 month prior to screening. 14. Uncontrolled hyperthyroidism 15. Diabetic patients with poorly controlled diabetes as evidenced by HbA1c > 8.5 % or not optimally treated for diabetes mellitus as judged by the investigator 16. Positive pregnancy test in females of childbearing potential 17. Female patients of childbearing potential who do not agree to use highly effective birth control methods 18. Pregnant or nursing (lactating) women. 19. Any medical condition that would, in the investigator’s judgment, prevent the patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures. |
1. Pacientes con macroadenoma complicado por síntomas compresivos 2. Período insuficiente de lavado de cualquier otro medicamento utilizado para disminuir los niveles de cortisol 3. Uso de otros fármacos en investigación en el momento del reclutamiento. 4. Antecedentes de hipersensibilidad a fármacos de la misma clase química que osilodrostat o de una clase similar. 5. Antecedentes de tumor maligno de cualquier sistema orgánico. 6. Deterioro renal de moderado a grave. 7. ALT o AST en suero >3 x LSN o bilirrubina total >1,5 x LSN. 8. Antecedentes de trombosis. 9. Factores de riesgo de prolongación del QTc o Torsade de Pointes. 10. Pacientes hipertensos con presión arterial no controlada. 11. Pacientes que se hayan sometido a una cirugía mayor durante el mes anterior. 12. Pacientes que se hayan sometido a cirugía hipofisaria transesfenoidal durante las 6 semanas anteriores a la selección, salvo que haya evidencia clara de hipercortisolemia persistente o cambios bioquímicos persistentes que concuerden con la enfermedad de Cushing. 13. Uso actual o previsto de glucocorticoides sistémicos un mes antes de la selección. 14. Hipertiroidismo no controlado. 15. Pacientes diabéticos con diabetes mal controlada indicada por una HbA1c >8,5 % o que no hayan sido tratados de manera óptima para la diabetes mellitus según el criterio del investigador. 16. Resultado positivo en una prueba de embarazo en mujeres en edad fértil). 17. Pacientes (mujeres) en edad fértil que no acepten utilizar métodos anticonceptivos altamente eficaces. 18. Mujeres embarazadas o en periodo de lactancia. 19. Cualquier enfermedad que, según el criterio del investigador, pudiera impedir la participación del paciente en este estudio clínico por motivos de seguridad o de cumplimiento de sus procedimientos. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic parameters of osilodrostat |
Parámetros farmacocinéticos de osilodrostat |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to Week 12 |
Hasta la semana 12 |
|
E.5.2 | Secondary end point(s) |
1. Proportion of patients with normal mUFC 2. mUFC absolute values and change from baseline 3. Safety and tolerability |
1. Proporción de pacientes con mUFC normal 2. Valores de mUFC absolutos y cambio repecto a la basal 3. Seguridad y tolerabilidad |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at week 6 and week 12 (or end of treatment) 2. up to week 48 3. up to week 48 |
1. En la semana 6 y semana 12 (o fin de tratamiento) 2. Hasta la semana 48 3. Hasta la semana 48 |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
Belgium |
Bulgaria |
Italy |
Slovenia |
Spain |
United Kingdom |
United States |
|
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
|
LVLS |
Último paciente última visita |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |