E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prader-Willi Syndrome |
Prader-Willi Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Prader-Willi Syndrome |
Prader-Willi Syndrome |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 | 10036476 |
E.1.2 | Term | Prader-Willi syndrome |
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 |
Core Period
Phase 2b
To demonstrate the efficacy of a 3-month treatment with livoletide as compared to placebo for reducing caregiver-observed food-related behavior as assessed by the Hyperphagia Questionnaire for Clinical Trials (HQ-CT).
Phase 3
To demonstrate the efficacy of a 6-month treatment with livoletide as compared to placebo for reducing caregiver-observed food-related behavior as assessed by HQ-CT. |
Perido Central
Fase 2b
Demostrar la eficacia de un tratamiento de 3 meses de duración con livoletida, en comparación con el placebo, para la reducción de la conducta alimentaria observada por el cuidador, evaluada mediante el Cuestionario de hiperfagia para ensayos clínicos (CH-EC).
Fase 3
Demostrar la eficacia de un tratamiento de 6 meses de duración con livoletida, en comparación con el placebo, para la reducción de la conducta alimentaria observada por el cuidador, evaluada mediante el CH-EC. |
|
E.2.2 | Secondary objectives of the trial |
Core Period
Phase 2b
To demonstrate the efficacy of 3-month treatment with livoletide as compared to placebo for:
− Reducing total body fat mass in overweight/obese patients with PWS;
− Reducing waist circumference (WC) in overweight/obese patients with PWS;
− Reducing body weight (BW) in overweight/obese patients with PWS.
Phase 3
To demonstrate the efficacy of 6-month treatment with livoletide as compared to placebo for:
− Reducing total body fat mass in overweight/obese patients with PWS;
− Reducing WC in overweight/obese patients with PWS;
− Reducing BW in overweight/obese patients with PWS.
Extension period:
- Maintenance of effects
- Pharmacokinetics |
Perido Central
Fase 2b
• Demostrar la eficacia del tratamiento de 3 meses de duración con livoletida, en comparación con el placebo en:
- La reducción de la masa corporal grasa total en pacientes obesos o con sobrepeso que padezcan el SPW.
- La reducción de la circunferencia de la cintura (CC) en pacientes obesos o con sobrepeso que padezcan el SPW.
- La reducción del peso corporal (PC) en pacientes obesos o con sobrepeso que padezcan el SPW.
Fase 3
Demostrar la eficacia del tratamiento de 6 meses de duración con livoletida, en comparación con el placebo en:
- La reducción de la masa corporal grasa total en pacientes obesos o con sobrepeso que padezcan el SPW.
- La reducción de la CC en pacientes obesos o con sobrepeso que padezcan el SPW.
- La reducción del PC en pacientes obesos o con sobrepeso que padezcan el SPW.
Periodo de extension
Mantenimiento de efectos
Farmacocinetica |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Phase 2b and Phase 3 Core
1. Diagnosis of PWS confirmed by deoxyribonucleic acid (DNA) methylation test.
2. Male and female patients 8 to 65 years of age, inclusive.
3. Have evidence of increased appetite or Hyperphagia
Phase 2b and 3 Extension
Patients must have participated in the core period. |
Fase 2b y Fase 3 Central
Diagnóstico del SPW, confirmado mediante el análisis de metilación del ácido desoxirribonucleico (ADN)
Pacientes de ambos sexos, de 8 a 65 años de edad (inclusive).
Presentar signos de aumento del apetito o hiperfagia
Fase 2b y Fase 3 Extension
Para poder participar en el período de extensión, los pacientes tendrán que haber finalizado el período central. |
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E.4 | Principal exclusion criteria |
Core Period
Phase 2b
1. History of chronic liver disease, such as cirrhosis or chronic hepatitis due to any cause, or suspected alcohol abuse.
2. History of significant cardiovascular disease including history of congestive heart failure CHF, New York Heart Association [NYHA] Class 3 or 4), angina pectoris, or
myocardial infarction (MI) within 6 months prior to screening.
3. Type 1 diabetes mellitus.
4. Glycated hemoglobin (HbA1c) >10%.
5. History of frequent hypoglycaemia.
Phase 3
A patient who enrolled in the Phase 2b part is not eligible for recruitment in the Phase 3 part. |
Perido Central
Fase 2b
1. Antecedentes de hepatopatía crónica, como cirrosis o hepatitis crónica debidas a cualquier causa o si existe la sospecha de alcoholemia.
2. Antecedentes de enfermedad cardiovascular importante, lo que incluye antecedentes de insuficiencia cardíaca congestiva (ICC de clase 3 o 4 según la asociación de cardiología de Nueva York [NYHA, New York Heart Association]), angina de pecho o infarto de miocardio (IM) en los 6 meses previos al screening.
3. Diabetes mellitus de tipo 1.
4. Glucohemoglobina (HbA1c) >10 %.
5. Antecedentes de hipoglucemia frecuente.
6.
“Please review Protocol”
Fase 3
Un paciente que sea incluido en la etapa de la fase IIb no es apto para participar en el reclutamiento de la etapa de la fase III. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Core Period
Phase 2b
• Change from baseline to the end of the 3-month Core Period in HQ-CT total score.
Phase 3
• Change from baseline to the end of the 6-month Core Period in HQ-CT total score. |
Periodo Central
Fase 2b
Variación desde el momento basal hasta el final del período central de 3 meses de la puntuación CH-EC total.
Fase 3
Variación desde el momento basal hasta el final del período central de 6 meses de la puntuación CH-EC total. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 2b - 3 months
Phase 3 - 6 months |
Fase 2b- 3 meses
Fase 3- 6 meses |
|
E.5.2 | Secondary end point(s) |
Core Period
Phase 2b
• Percentage change from baseline to the end of the 3-month Core Period in total body fat mass in overweight/obese patients with PWS;
• Change from baseline to the end of the 3-month Core Period in waist circumference in overweight/obese patients with PWS;
• Percentage change from baseline to the end of the 3-month Core Period in body weight in overweight/obese patients with PWS
Phase 3
• Percentage change from baseline to the end of the 6-month Core Period in total body fat mass in overweight/obese patients with PWS;
• Change from baseline to the end of the 6-month Core Period in waist circumference in overweight/obese patients with PWS;
• Percentage change from baseline to the end of the 6-month Core Period in body weight in overweight/obese patients with PWS. |
Periodo Central
Fase 2b
• Variación porcentual desde el momento basal hasta el final del período central de 3 meses de la masa corporal grasa total en pacientes obesos o con sobrepeso que padezcan el SPW.
• Variación desde el momento basal hasta el final del período central de 3 meses de la CC en pacientes obesos o con sobrepeso que padezcan el SPW.
• Variación porcentual desde el momento basal hasta el final del período central de 3 meses del PC en pacientes obesos o con sobrepeso que padezcan el SPW.
Fase 3
• Variación porcentual desde el momento basal hasta el final del período central de 6 meses de la masa corporal grasa total en pacientes obesos o con sobrepeso que padezcan el SPW.
• Variación desde el momento basal hasta el final del período central de 6 meses de la CC en pacientes obesos o con sobrepeso que padezcan el SPW.
• Variación porcentual desde el momento basal hasta el final del período central de 6 meses del PC en pacientes obesos o con sobrepeso que padezcan el SPW. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase 2b - 3 months
Phase 3 - 6 months |
Fase 2b- 3 meses
Fase 3- 6 meses |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 |
E.6.9 Dose response is applicable to Phase 2b only |
E.6.9 Respuesta de la dosis es applicable solo en la Fase 2b |
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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) | 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 | 3 |
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 |
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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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The end of study is defined as the last visit of the last patient (LPLV) in the trial globally. |
Fin del studio es definido como la última visita del ultimo paciente (LPLV) en el studio global. |
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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 | 24 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 24 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |