E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Self-injurious behavior in subjects with Lesch-Nyhan Disease (LND). |
Conducta autolesiva en sujetos con el síndrome de Lesch-Nyhan (LND). |
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E.1.1.1 | Medical condition in easily understood language |
Self-injurious behavior in subjects with Lesch-Nyhan Disease (LND). |
Conducta autolesiva en sujetos con el síndrome de Lesch-Nyhan (LND). |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behaviours [F01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024245 |
E.1.2 | Term | Lesch-Nyhan 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 |
To assess the efficacy of ecopipam to reduce self-injurious behaviors (SIB) in adults and children with Lesch-Nyhan Disease (LND) in an outpatient setting. |
El objetivo principal de este estudio es evaluar la eficacia del ecopipam para reducir las conductas autolesivas (SIB) en adultos y niños con LND en un entorno de consultas externas. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of withdrawal, maintenance, and safety of ecopipam in subjects with Lesch-Nyhan Disease (LND). |
Los objetivos secundarios de este estudio son evaluar los efectos que se derivan de retirar o mantener, y la seguridad del ecopipam en sujetos con LND. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects must have classic LND as defined by (a) characteristic clinical syndrome (evidence of overproduction of uric acid, severe generalized dystonia, frequent and persistent SIB, and cognitive impairment) and (b) laboratory confirmation for mutation of the HPRT gene or severe deficiency of the associated enzyme. 2. Subjects must have a minimum combined score of 20 on the BPI SIB subscales for frequency and severity as assessed by the caregiver. 3. Subjects must have a minimum score of 4 on the Physician?s Global Impression (PGI) severity scale. 4. Subjects must be ?6 years old. 5. Subject must have a body weight greater than 10 kg. 6. Although females with LND are extremely rare, they are occasionally encountered. For a woman to be eligible she must be postmenopausal (>12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie, oral contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for the duration of their participation in the study. Women of childbearing potential must agree to use contraception for 30 days after their last dose of study drug. 7. Sexually active male subjects must use a barrier method of contraception during the study and agree to continue the use of male contraception for at least 30 days after the last dose of study drug. 8. Subject and/or legal guardian must execute a written Informed Consent and/or Assent. |
1. Los sujetos deben tener el síndrome de Lesch-Nyhan (LND) clásico según lo definido por (a) síndrome clínico característico (evidencia de hiperproducción de ácido úrico, distonía grave generalizada, SIB frecuente y persistente, y deterioro cognitivo) y (b) confirmación de laboratorio de mutación del gen HPRT o deficiencia grave de la enzima asociada. 2. Los sujetos deben tener una puntuación mínima combinada de 20 en las subescalas SIB del BPI en cuanto a la frecuencia y gravedad según lo valorado por el cuidador. 3. Los sujetos deben tener una puntuación mínima de 4 en la escala de gravedad de impresión global del médico (Physician?s Global Impression [PGI]). 4. Los sujetos deben tener ? 6 años de edad. 5. El sujeto debe tener un peso corporal mayor de 10 kg. 6. Aunque es extremadamente raro que haya mujeres con LND, ocasionalmente se encuentran. Para que una mujer sea idónea debe ser postmenopáusica (> 12 meses sin menstruaciones) o estar esterilizada quirúrgicamente (por histerectomía u ooferectomía bilateral) o debe estar utilizando métodos eficaces de contracepción (anticonceptivos orales, dispositivo intrauterino, método de doble barrera de preservativo y espermicida) y estar de acuerdo en seguir usando la contracepción durante su participación en el estudio. Las mujeres con potencial de fecundidad deben aceptar el uso de la contracepción hasta 30 días después de su última dosis del fármaco del estudio. 7. Los hombres sexualmente activos deben utilizar un método de barrera de contracepción durante el estudio y estar de acuerdo en seguir usando anticonceptivos masculinos durante al menos 30 días después de la última dosis del fármaco del estudio. 8. El sujeto o tutor legal debe completar un consentimiento o asentimiento informado por escrito. |
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E.4 | Principal exclusion criteria |
1. Subjects who have participated in a clinical trial (other than PSY101) and have received an investigational drug within 30 days prior to the start of the study. 2. Subjects who are on neuroleptics or dopamine depleting agents. 3. Subjects who are currently treated with medications for seizures 4. Subjects with impaired renal function as defined by a serum creatinine >1.5 mg/dL. 5. Subjects with medical comorbidities that may interfere with completion of the study. 6. Women of childbearing potential who are currently pregnant or lactating. |
1. Sujetos que hayan participado en un ensayo clínico (distinto al PSY101) y hayan recibido un fármaco en investigación en el periodo de 30 días antes del inicio del estudio. 2. Sujetos que reciben neurolépticos o agentes para la reducción de dopamina. 3. Sujetos que actualmente se tratan con medicamentos para convulsiones. 4. Sujetos con función renal alterada según lo definido por creatinina en suero >1.5 mg/dL. 5. Sujetos con comorbilidades médicas que puedan interferir en la finalización del estudio. 6. Mujeres con potencial de fecundidad que estén embarazadas o que amamantan. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Behavior Problems Inventory (BPI) SIB subscales for frequency and severity as assessed by the caregiver. |
El criterio principal de valoración es el inventario de conductas problemáticas o BPI (subescalas de SIB - total de frecuencia y gravedad) según la valoración del cuidador. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The caregiver will complete the BPI each week. |
El cuidador completará el BPI cada semana. |
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E.5.2 | Secondary end point(s) |
Vital signs, Caregiver Global Impression (CGI) improvement, adverse events (AEs). |
Signos vitales, mejora de CGI (impresión global del cuidador), efectos adversos. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, once during each tratment period (1-3), once during follow-up, twice during open-label treatment period, once at the end of the study. |
Momento basal, una vez durante periodo de tratamiento 1-3, una vez durante periodo de seguimiento, dos veces durante periodo de tratamiento abierto, una vez al fin del estudio. |
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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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Doble ciego con una ampliación abierta. |
Double-blind with an open-label extension. |
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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
| 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 | 3 |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |