E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Acromegaly is typically caused by a growth hormone (GH) secreting tumor in the pituitary. |
L'Acromegalia è tipicamente causata da un tumore nell'ipofisi che causa la produzione di un ormone della crescita (GH) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
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 effect of paltusotine versus placebo on IGF 1 response |
Valutare l'effetto di paltusotina rispetto al placebo sulla risposta dell' IGF-1 |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of paltusotine versus placebo on IGF 1 level To evaluate the effect of paltusotine versus placebo on GH response To evaluate the effect of paltusotine versus placebo on acromegaly symptoms. |
Valutare l'effetto di paltusotina rispetto al placebo sul livello di IGF 1 Valutare l'effetto di paltusotina rispetto al placebo sulla risposta del GH Valutare l'effetto di paltusotina rispetto al placebo sui sintomi di acromegalia |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects greater than or equal to 18 years of age 2. Confirmed diagnosis of acromegaly and controlled (as measured by IGF-1 less than or equal to 1.0×ULN) via stable dose of protocol defined somatostatin receptor ligand therapy. 3. Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, or using effective method(s) of birth control. 4. Willing to provide signed informed consent. |
1- Soggetti maschili e femminili con eta' maggiore o uguale a 18 anni 2-Confermata diagnosi di acromegalia e controllata (misurata da IGF-1 minore o uguale a 1.0×ULN) tramite una dose stabile di terapia con ligando del recettore della somatostatina definita dal protocollo. 3- I soggetti di sesso femminile non devono essere in gravidanza e non devono allattare, essere chirurgicamente sterili, in post-menopausa o devono utilizzare metodi efficaci di controllo delle nascite. 4- Disponibilità a firmare il consenso informato |
|
E.4 | Principal exclusion criteria |
1. Treatment naïve acromegaly subjects 2. Prior treatment with paltusotine. 3. History of pituitary radiation therapy. 4. History or presence of malignancy except adequately treated basal cell and squamous cell carcinomas of the skin within the past 5 years 5. Use of any investigational drug within the past 30 days or 5 half-lives, whichever is longer. 6. Known history of HIV, hepatitis B, or active hepatitis C. 7. History of alcohol or substance abuse in the past 12 months. 8. Cardiovascular conditions or medications associated with prolonged QT or those which predispose subjects to heart rhythm abnormalities. 9. Subjects with symptomatic cholelithiasis. 10.Subjects with clinically significant abnormal findings during the Screening Period, or any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the subject's safety or ability to complete the study 11. Subjects currently taking pasireotide LAR (within 24 weeks prior to Screening) or pegvisomant, dopamine agonists, or short acting somatostatin analogs (with 12 weeks prior to Screening). |
1.Soggetti con acromegalia naïve al trattamento 2.Precedente trattamento con paltusotina. 3.Anamnesi di radioterapia dell'ipofisi 4.Anamnesi o presenza di neoplasie maligne, ad eccezione dei carcinomi a cellule basali e squamocellulari della pelle adeguatamente trattati negli ultimi 5 anni. 5.Soggetti che hanno ricevuto un farmaco sperimentale nei ultimi 30 giorni o 5 emivite, a seconda di quale sia il periodo piu' lungo. 6.Anamnesi nota di HIV, epatite B o epatite C attiva 7.Anamnesi nota di abuso di alcol o sostanze negli ultimi 12 mesi 8. Condizioni cardiovascolari o farmaci associati a QT prolungato o quelli che predispongono i soggetti ad anomalie del ritmo cardiaco 9. Soggetti con colelitiasi sintomatica 10. Soggetti con risultati anormali clinicamente significativi durante il periodo di screening o qualsiasi altra condizione medica o risultati di laboratorio che, a parere dello sperimentatore, potrebbero mettere a rischio la sicurezza del soggetto o la capacità di completare lo studio 11.Soggetti che assumono attualmente pasireotide LAR (entro 24 settimane prima dello screening) o pegvisomant, agonisti della dopamina o analoghi della somatostatina a breve durata d'azione (con 12 settimane prima dello screening). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Proportion of subjects who maintain biochemical response in IGF 1 (less than or equal to 1.0×the upper limit of normal [ULN]) at the End of the Randomized Control Phase (EOR) |
- Percentuale di soggetti che mantengono una risposta biochimica a livello di IGF 1 (minore o uguale a 1,0 × limite superiore della norma [ULN]) alla fine della fase randomizzata e controllata (EOR) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
36 weeks for the primary endpoint. |
36 settimane per l'endpoint primario |
|
E.5.2 | Secondary end point(s) |
- Change from baseline in IGF-1, in units of ULN, to EOR - Proportion of subjects with GH <1.0 ng/mL at Week 34, out of those who had GH <1.0 ng/mL at Screening - Change from baseline in Total Acromegaly Symptoms Diary (ASD) score to EOR. |
- Variazione dalla baseline all'EOR nell'IGF-1, in unità ULN - Percentuale di soggetti con GH <1,0 ng/mL alla Settimana 34, su quelli con GH <1,0 ng/mL allo Screening -Variazione dalla baseline all'EOR nel punteggio totale del Diario dei sintomi dell'acromegalia (ASD) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
36 weeks for the secondary endpoint. |
36 settimane per l'endpoint secondario |
|
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 | No |
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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | Information not present in EudraCT |
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 |
Brazil |
Israel |
Peru |
Russian Federation |
Serbia |
United States |
Austria |
Belgium |
Bulgaria |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
United Kingdom |
Argentina |
|
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
|
Last visit of the last subject in the study |
L'ultima visita dell'ultimo soggetto nello studio |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |