E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Erosive Esophagitis in paediatric subjects aged 1 to 11 years |
Esofagite erosiva in soggetti pediatrici di età compresa tra 1 e 11 anni |
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E.1.1.1 | Medical condition in easily understood language |
Inflammation/swelling/irritation of the esophagus in children |
Infiammazione / gonfiore / irritazione all'esofago nei bambini |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063657 |
E.1.2 | Term | Erosive esophagitis |
E.1.2 | System Organ Class | 100000004856 |
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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 |
1) To assess the safety and effectiveness of treatment with QD oral administration of dexlansoprazole 30 or 60 mg for 8 to 12 weeks in pediatric subjects aged 1 to 11 years, inclusive, with EE.
2) To assess the safety and effectiveness of dexlansoprazole 15 or 30 mg compared to placebo in maintenance of healed EE for 16 weeks. |
1) Valutare sicurezza ed efficacia del trattamento con dexlansoprazolo somministrato QD per via orale alla dose di 30 o 60 mg per 8-12 settimane in soggetti pediatrici di età compresa tra 1 e 11 anni inclusi, affetti da EE.
2) Valutare sicurezza ed efficacia di dexlansoprazolo 15 o 30 mg rispetto al placebo nel mantenimento dell’EE cicatrizzata per 16 settimane.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Subjects who have a medical history of GERD symptoms for at least 3 months prior to Screening and history of at least 1 failed attempted withdrawal of prior PPI or acid suppressive therapy with return of symptoms upon withdrawal.
2) Reported symptoms of hurting or burning in the stomach, chest, or throat on at least 3 of any 7 consecutive days as recorded in the electronic daily diary (eDiary) during Screening.
3) The subject has endoscopic evidence of EE (HD Grade >2) based on an endoscopy performed during the Screening Period or within 1 week prior to signing informed consent and assent (as applicable). |
1) Soggetti con anamnesi di sintomi di GERD presenti da almeno 3 mesi al momento dello screening e con anamnesi di almeno 1 tentativo fallito di sospensione della precedente terapia con IPP o antiacidi caratterizzato dalla ripresentazione dei sintomi alla sospensione.
2) Sintomi riferiti di dolore o bruciore di stomaco, torace o gola accusati per almeno 3 giorni su 7 consecutivi, secondo quanto registrato nel diario elettronico giornaliero durante lo screening.
3) Il soggetto presenta evidenza endoscopica di EE (di grado HD >2) in base alla valutazione endoscopica effettuata durante il periodo di screening o nella settimana precedente la firma del consenso informato e dell’assenso (secondo il caso).
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E.4 | Principal exclusion criteria |
1) Subjects who have a history of hypersensitivity or allergies to dexlansoprazole or any component of dexlansoprazole or antacid or any PPI (including lansoprazole, omeprazole, rabeprazole, pantoprazole, or esomeprazole).
2) Subjects with evidence of cardiovascular, pulmonary, central nervous system, hepatic, hematopoietic, renal, metabolic, endocrine or gastrointestinal disease, or serious allergy, asthma, or allergic skin rash that suggests clinically significant, uncontrolled underlying disease or condition (other than the disease being studied), which may impact the ability of the subject to participate or potentially confound the study results or clinically significant finding from physical examinations or clinical laboratory results as deemed by the investigator.
3) Subjects with known history ofBarrett’s esophagus with dysplastic changes in the esophagus. Subjects with history of the following; eosinophilic esophagitis (EoE) or histologic findings suggestive of EoE (>15 eosinophils per high-powered field [HPF]), a history of celiac disease or tests positive for tissue transglutaminase antibody (tTG) antibody or confirmed disease by histology, inflammatory bowel disease, or irritable bowel syndrome.
4) Subjects with active gastric or duodenal ulcers within 4 weeks prior to Day -1.
5) Subjects who are required to take prescription or nonprescription medications as listed in Excluded Medications and Treatment Section of the protocol.
6) Subjects who test positive for Helicobacter pylori (H. pylori.) However, subjects who are positive and have received therapeutically approved eradication therapy within the past 6 months will be allowed to participate. |
1) Soggetti con anamnesi di ipersensibilità o allergie al dexlansoprazolo o a uno qualsiasi dei componenti del dexlansoprazolo oppure agli antiacidi o agli IPP (inclusi lansoprazolo, omeprazolo, rabeprazolo, pantoprazolo o esomeprazolo).
2) Soggetti con evidenza di patologie del sistema cardiovascolare, nervoso centrale, epatico, emopoietico, renale, metabolico, endocrino o gastrointestinale, oppure grave allergia, asma o eruzione cutanea allergica che indichi una patologia o un’affezione sottostante clinicamente significativa e non controllata (diversa dalla malattia in studio), che potrebbe pregiudicare la capacità del soggetto di partecipare allo studio o che potrebbe potenzialmente confondere i risultati dello studio, oppure esiti clinicamente significativi all’esame obiettivo o nei risultati di laboratorio, secondo il parere dello sperimentatore.
3) Soggetti con nota anamnesi di esofago di Barrett con alterazioni displastiche dell’esofago. Soggetti con anamnesi di una delle seguenti patologie: esofagite eosinofila (EE) o reperti istologici indicanti EE (>15 eosinofili per campo ad alto ingrandimento [High Power Field, HPF]), antecedenti di malattia celiaca o risultati positivi al test per gli anticorpi anti-transglutaminasi tissutali (Tissue Transglutaminase, tTG) o malattia confermata istologicamente, malattia infiammatoria intestinale o sindrome dell’intestino irritabile.
4) Soggetti con ulcere gastriche o duodenali attive nelle 4 settimane precedenti il giorno -1.
5) Soggetti che necessitano di assumere farmaci su prescrizione o da banco che sono elencati nel paragrafo Farmaci e trattamenti esclusi del protocollo.
6) Soggetti che risultano positivi al test dell’Helicobacter pylori (H. pylori.) Potranno però partecipare i soggetti positivi che hanno ricevuto una terapia di eradicazione terapeuticamente approvata negli ultimi 6 mesi.
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Percentage of subjects with healing of EE by Week 12 as assessed by endoscopy.
2) Percentage of subjects who maintained healed EE for 16 weeks among the subjects who were healed by Week 12 as assessed by endoscopy. |
• Percentuale di giorni senza dolore o bruciore allo stomaco, al torace o alla gola durante le 12 settimane di trattamento.
• La percentuale di soggetti che mantengono l’EE cicatrizzata per 16 settimane tra i soggetti che avevano fatto rilevare una cicatrizzazione entro la settimana 12, secondo valutazione endoscopica.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 8 for initial assessment
Week 12 as maximum duration of healing phase of the trial
Week 24 or 28 during maintenance phase (depending on when healing phase is considered complete) |
Settimana 8 per la valutazione iniziale
Settimana 12 come durata massima di fase di cicatrizzazione dello studio
Settimana 24 o 28 durante la fase di mantenimento (in base a quando la fase di cicatrizzazione è considerata completa)
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E.5.2 | Secondary end point(s) |
1) Percentage of days without hurting or burning in the stomach, chest or throat over the first 8 or 12 weeks of treatment.
2) Percentage of days without hurting or burning in the stomach, chest or throat over Weeks 8 to 24 or Weeks 12 to 28 among subjects who were healed by Week 12. |
1) La percentuale di giorni senza dolore o bruciore a stomaco, torace o gola nelle prime 8-12 settimane di trattamento.
2) La percentuale di giorni senza dolore o bruciore a stomaco, torace o gola durante le settimane dalla 8 alla 24 o dalla 12 alla 28 tra i soggetti con cicatrizzazione rilevata entro la settimana 12.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 8 for initial assessment
Week 12 as maximum duration of healing phase of the trial
Week 24 or 28 during maintenance phase (depending on when healing phase is considered complete) |
Settimana 8 per la valutazione iniziale
Settimana 12 come durata massima di fase di cicatrizzazione dello studio
Settimana 24 o 28 durante la fase di mantenimento (in base a quando la fase di cicatrizzazione è considerata completa)
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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 | 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) | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Dosi comparative dello stesso IMP nella fase di cicatrizzazione e uso di placebo nella fase di mante |
Compartive doses of same IMP during healing phase and use of placebo in maintenance phase |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Belgium |
Brazil |
Israel |
Italy |
Mexico |
Poland |
Portugal |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 24 |