E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
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 investigate the effect of treatment on GH and IGF-1 concentrations. |
Investigar el efecto del tratamiento en las concentraciones de GH e IGF-1 |
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E.2.2 | Secondary objectives of the trial |
- To investigate the biochemical response of ITF2984, defined as a reduction in (random) GH < 1.0 mcg/l and/or normalization of IGF-1. - To investigate the biochemical response of ITF2984, defined as a reduction of GH to no more than 2.5 mcg/l and/or normalization of IGF-1. - To evaluate variation of signs and symptoms of acromegaly at the end of each month of treatment in comparison with basal status. - To investigate the pharmacokinetic (PK) profile of ITF2984 and Octreotide - To compare the effects on GH and IGF1 circulating levels of different doses of ITF2984 - To compare the effects on GH and IGF1 circulating levels of ITF2984 and Octreotide |
- Investigar la respuesta bioquímica de ITF2984, definida como una reducción de GH (aleatoria) <1,0 mcg/l y/o normalización de IGF-1. - Investigar la respuesta bioquímica de ITF2984, definida como una reducción de GH a no más de 2,5 mcg/l y/o normalización de IGF-1. - Evaluar la variación en los signos y síntomas de la acromegalia al final de cada mes de tratamiento en comparación con la situación basal. - Investigar el perfil farmacocinético (FC) de ITF2984 y octreótido. - Comparar los efectos de diferentes dosis de ITF2984 en los niveles circulantes de GH e IGF1. - Comparar los efectos de ITF2984 y octreótido en los niveles circulantes de GH e IGF1. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed written informed consent. - Patients with active acromegaly due to a pituitary adenoma. Active acromegaly should be confirmed by 2h five point mean GH level higher than 5 mcg/liter, lack of suppression of GH nadir to less than 1 mcg/liter after oral glucose tolerance test, and elevated IGF-1 for age and sex-matched controls. - Patients aged between 18 to 80 years old inclusive. - Patients treated with previous surgery and/or medical therapy or previously untreated (de novo). For patients who had previously received medical therapy for acromegaly a washout periods before study entry of 3 months for long-acting formulation of somatostatin analogs and 2 weeks for octreotide sc must be foreseen. Partial responder means a significant decrease (>50%), without achievement of control of GH and/or IGF-1 levels and/or >20 % tumor shrinkage after at least 6 months of SRL therapy. - Patients with GH level and IGF-1 level for age and sex-matched controls out of range at baseline. |
- Documento de consentimiento informado por escrito firmado. - Pacientes con acromegalia activa debido a un adenoma hipofisario. Se debe confirmar la acromegalia activa por medio de los niveles medios de GH de cinco determinaciones en un periodo de 2 horas superiores a 5 mcg/litro, falta de inhibición del nivel mínimo de GH a menos de 1 mcg/litro después del test de tolerancia a la glucosa oral, e IGF-1 elevado para los controles emparejados por edad y sexo. - Pacientes con edades comprendidas entre 18 y 80 años inclusive. - Pacientes tratados con cirugía y/o tratamiento médico previos o no tratados previamente (de novo). En el caso de los pacientes que habían recibido tratamiento médico previo para la acromegalia se debe prever un periodo de reposo farmacológico antes de entrar en el estudio de 3 meses en el caso de los análogos de la somatostatina de acción prolongada y 2 semanas en el caso de la octreótido SC. Respondedor parcial significa una disminución importante (>50 %), sin alcanzar el control de los niveles de GH y/o IGF-1 y/o una reducción del tumor >20 % tras al menos 6 meses de tratamiento con ligandos de los receptores de la somatostatina. - Pacientes con niveles de GH e IGF-1 para controles emparejados por edad y sexo fuera del intervalo al inicio. |
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E.4 | Principal exclusion criteria |
- Patients undergone pituitary surgery within the prior 6 months. - Patients who have received pituitary radiotherapy (within last 10 years). - Patients with compression of the optic chiasm causing any visual field defect. - Patients who require a surgical intervention for relief of any sign or symptom associated with tumor compression. - Patients with uncontrolled diabetes defined as having a fasting glucose > 150 mg/dL (8.3 mmol/L) or HbA1c ? 8% (Patients can be rescreened after diabetes is brought under adequate control). - Patients with significant cardiovascular morbidity within the three months preceding enrollment. - Symptomatic cholelithiasis, gallstone or chronic liver disease. - Clinically significant GI, renal or hepatic disease (in the opinion of investigator). - AST and/or ALT>2ULN. - Active HBV and/or active HCV infection. - Patients who have a history of alcohol or drug abuse in the six-month period prior to the enrollment visit. - Known hypothyroidism or hypocortisolism not adequately treated with a stable dose of thyroid or steroid hormone replacement therapy for at least the previous 3 months. - Known hypersensitivity to any of the study medications, or components thereof or a history of drug or other allergy that in the opinion of the Investigator contraindicates their participation. - Female patients who are pregnant or lactating, and female patient who are of childbearing potential or male patient with female partners of childbearing potential who do not accept the contraception requirements reported in the protocol. - Patients who have participated in any clinical investigation with an Investigational drug within 3 months before study entry. - Current or recent (< 2 months) therapy with pegvisomant or cabergoline. |
- Pacientes que se han sometido a cirugía hipofisaria en los 6 meses anteriores. - Pacientes que han recibido radioterapia hipofisaria (en los últimos 10 años). - Pacientes con compresión del quiasmo óptico que cause cualquier defecto del campo visual. - Pacientes que requieren una intervención quirúrgica para el alivio de cualquier signo o síntoma asociado a la compresión del tumor. - Pacientes con diabetes no controlada definida como una glucosa en ayunas >150 mg/dl (8,3 mmol/l) o HbA1c ?8 %. (Se puede volver a seleccionar a los pacientes una vez que la diabetes esté adecuadamente controlada). - Pacientes con morbilidad cardiovascular significativa en los tres meses anteriores a la inclusión. - Colelitiasis, cálculo biliar o enfermedad hepática crónica sintomáticos. - Enfermedad GI, renal o hepática clínicamente significativa (en opinión del investigador). - ASAT y/o ALAT >2 veces el límite superior de la normalidad. - Infección activa por el VHB y/o VHC. - Pacientes con antecedentes de alcoholismo o drogadicción en los 6 meses anteriores a la visita de inclusión. - Hipotiroidismo o hipocortisolismo conocidos no tratados adecuadamente con una dosis estable de terapia restitutiva de hormona tiroidea o esteroidea durante al menos los 3 meses previos. - Hipersensibilidad conocida a alguno de los medicamentos del estudio o componentes de los mismos o historia de alergias al medicamento u otras alergias que en opinión del investigador contraindiquen la participación. - Mujeres embarazadas o en periodo de lactancia, y mujeres en edad fértil u hombres cuyas parejas estén en edad fértil que no acepten los requisitos relativos a los anticonceptivos descritos en el protocolo (más información en la sección 4.3.2). - Pacientes que han participado en cualquier investigación clínica con un medicamento en investigación en los 3 meses anteriores a entrar en el estudio. - Tratamiento actual o reciente (<2 meses) con pegvisomant o cabergolina. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change of GH and/or IGF-1 levels at the end of each month of treatment. |
- Cambio en los niveles de GH y/o IGF-1 al final de cada mes de tratamiento. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of each month of treatment |
al final de cada mes de tratamiento |
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E.5.2 | Secondary end point(s) |
- Number and percentage of patients with reduction of GH < 1.0 mcg/l and/or normalization of IGF-1 at the end of each month of treatment. - Number and percentage of patients with reduction in GH <2.5 mcg/l and/or normalization of IGF-1 at the end of each month of treatment. - Number and percentage of patients with improvement of signs and symptoms of acromegaly at the end of each month of treatment. |
- Número y porcentaje de pacientes con reducción de GH <1,0 mcg/l y/o normalización de IGF-1 al final de cada mes de tratamiento. - Número y porcentaje de pacientes con reducción de GH <2,5 mcg/l y/o normalización de IGF-1 al final de cada mes de tratamiento. - Número y porcentaje de pacientes con mejoría de los signos y síntomas de la acromegalia al final de cada mes de tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of each month of treatment |
al final de cada mes de tratamiento |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | |
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 |