E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Carcinoid Syndrome |
Sindrome da carcinoide |
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E.1.1.1 | Medical condition in easily understood language |
A complex of symptoms due to a carcinoid tumor producing too many hormones which cause multiple symptoms like diarrhea, flushing, urgent need for a bowel movement. |
Un complesso di
sintomi a causa di tumore carcinoide che produce troppi ormoni che causano molteplici
sintomi come diarrea, vampate di calore,urgente bisogno di evacuazioni intestinali
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007270 |
E.1.2 | Term | Carcinoid syndrome |
E.1.2 | System Organ Class | 10014698 - Endocrine 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 |
The primary objective of this study is to evaluate the long-term safety and tolerability of orally administered telotristat etiprate |
L'obiettivo primario di questo studio consiste nella valutazione della sicurezza e tollerabilità a lungo termine di telotristat etiprato
somministrato per via orale
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E.2.2 | Secondary objectives of the trial |
To evaluate long-term changes in patients’ quality of life (QOL) |
Valutazione dei cambiamenti a lungo termine della qualità di vita (QOL) dei pazienti |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following criteria to be considered eligible to participate in the study:
1. Ongoing participation in a Phase 2 (eg, LX1606.1-202-CS, LX1606.1-203-CS) or Phase 3 (eg, LX1606.1-301-CS, LX1606.1-303-CS) study
2. Patients of childbearing potential must agree to use an adequate method of contraception (defined as having a failure rate of <1% per year) during the study and for 12 weeks after the Follow-up visit. Adequate methods of contraception for patients or partner include condoms with spermicide gel, diaphragm with spermicide gel, coil (intrauterine device), surgical sterilization, vasectomy, oral contraceptive pill, depot progesterone injections, progesterone implant, and abstinence during the study and for 12 weeks after the Follow-up Visit.
a. Childbearing potential is defined as those who have not undergone surgical sterilization, or those who are not considered postmenopausal. Postmenopause is defined as absence of menstruation for at least 2 years. If necessary, follicle-stimulating hormone (FSH) results >50 IU/L at entry are confirmatory in the absence of a clear postmenopausal history.
3. Ability and willingness to provide written informed consent prior to participation in any study-related procedure
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Partecipazione in corso a uno studio di fase II (ad es., LX1606.1- 202-CS, LX1606.1-203-CS) o fase 3 (ad es., LX1606.1-301-CS, LX1606.1-303-CS)
Le pazienti in età fertile devono accettare di usare un metodo contraccettivo adeguato (che abbia un tasso di fallimento inferiore all’1% annuo) durante lo studio e per 12 settimane dopo la visita di follow-up. I metodi contraccettivi adeguati per pazienti o partner includono preservativi con gel spermicida, diaframma con gel spermicida, spirale (dispositivo intrauterino), sterilizzazione chirurgica, vasectomia, pillola contraccettiva orale, iniezioni di progesterone a lento rilascio, impianto di progesterone e astinenza durante lo studio e per 12 settimane dopo la visita di follow-up.
a. Per donne in età fertile s’intendono donne che non hanno subito sterilizzazione chirurgica o che non sono considerate in post-menopausa. Per post-menopausa s’intende l’assenza di mestruazioni per almeno 2 anni. Se necessario, in assenza
di una chiara anamnesi di postmenopausa, per la conferma all'ingresso saranno sufficienti livelli di ormone follicolo stimolante (FSH) >50 IU/L.
Capacità e disponibilità del paziente a fornire il proprio consenso informato per iscritto prima di partecipare a qualsiasi procedura legata allo studio.
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from participating in the study:
1. Major protocol violations or tolerability concerns in a Phase 2 (eg, LX1606.1-202-CS, LX1606.1-203-CS) or Phase 3 (eg, LX1606.1-301-CS, LX1606.1-303-CS) study
2. Positive pregnancy test
3. Presence of any clinically significant findings at entry for medical history, laboratory values, or physical examination (relative to patient population) that, in the Investigator’s or Medical Monitor’s opinion, would compromise patient safety or the outcome of the study
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Importanti violazioni del protocollo o problemi di tollerabilità in uno studio di fase II (ad es., LX1606.1-202-CS, LX1606.1-203- CS) o fase 3 (ad es., LX1606.1-301-CS, LX1606.1-303-CS)
2. Positività al test di gravidanza
3. Presenza di qualsiasi riscontro clinicamente significativo all'ingresso riguardante l’anamnesi patologica, i valori di laboratorio o l'esame obiettivo (rispetto alla popolazione di pazienti) che, secondo il parere dello sperimentatore, comprometterebbe la sicurezza del paziente o l’esito dello studio
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is to evaluate the long-term safety and tolerability of orally administered telotristat etiprate.
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L'end point primario di efficacia è di valutare la sicurezza e la tollerabilità a lungo termine di telotristat etiprato
somministrato per via orale
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|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at each visit and the final analysis will be done at the end of the study |
ad ogni visita e l'analisi finale sarà effettuata alla fine dello studio |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoint is to evaluate changes in patients’ QOL over multiple years of therapy.
Safety endpoints are as follows:
• Incidence of TEAEs, suspected adverse reaction, AEs leading to discontinuation from the study, SAEs, and deaths
• Actual and change from Baseline in clinical laboratory results
• Actual and change from Baseline in vital signs results
• Actual and change from Baseline in physical examinations
• Actual and change from Baseline in ECG findings
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Gli end point secondary di efficacia
di valutare i cambiamenti a lungo termine della qualità di vita (QOL) dei pazienti
Gli End point di sicurezza sono:
•Incidenza di TEAE, sospette reazioni avverse, Eventi avversi che
portano a interrompere lo stduio, Eventi avversi seri e la morte
•Attuale e variazione dal basale dei risultati clinici di laboratorio,
•Attuale e variazione dal basale dei segni vitali,
•Attuale e variazione dal basale degli esami obiettivi
•Attuale e variazione dal basale dei tracciati dell'ECG
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at each visit and the final analysis will be done at the end of the study |
ad ogni visita e l'analisi finale sarà effettuata alla fine dello studio |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
due differenti dosi di LX1606 |
Two different doses of LX1606 |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 |
Australia |
Belgium |
Brazil |
Canada |
France |
Germany |
Israel |
Italy |
Netherlands |
Spain |
Sweden |
United Kingdom |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |