E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Endometriosis Associated Pain |
Dolore associato all’endometriosi da Moderato a Intenso |
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E.1.1.1 | Medical condition in easily understood language |
Endometriosis Associated Pain |
Dolore associato all’endometriosi |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014788 |
E.1.2 | Term | Endometriosis related pain |
E.1.2 | System Organ Class | 100000004872 |
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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 |
The primary objective of this 6-month extension study is to evaluate the continued safety, efficacy and tolerability of the 150 mg QD and 200 mg BID doses of elagolix (ABT-620) for up to 12 months in the management of moderate to severe endometriosis-associated pain. Safety and tolerability will include assessments of BMD via dual-energy x-ray absorptiometry (DXA) including effects of long term treatment and post-treatment recovery during an up to 12-month Post-Treatment Period and evaluation of endometrial health via transvaginal ultrasound (TVU). |
L’obiettivo primario di questo studio di estensione della durata di 6 mesi è valutare la sicurezza e la tollerabilità a lungo termine della dose di 150 mg una volta al giorno (QD) e 200 mg due volte al giorno (BID) di elagolix (ABT-620) per un periodo fino a 12 mesi, nella gestione del dolore associato all’endometriosi da moderato a intenso. La sicurezza e la tollerabilità comprenderanno valutazioni della densità minerale ossea (DMO) tramite assorbimetria a raggi X a doppia energia (DEXA), inclusi gli effetti del trattamento a lungo termine e il recupero post-trattamento, per un periodo post-trattamento di durata fino a 12 mesi e una valutazione dello stato di salute dell’endometrio tramite ecografia transvaginale (TVU) |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the population PK and PD of elagolix. |
Un obiettivo supplementare dello studio è valutare la farmacocinetica di popolazione e la farmacodinamica di elagol |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject has voluntarily signed and dated the informed consent form (ICF), approved by an Institutional Review Board/Ethics Committee (IRB/EC) prior to initiation of any study-specific procedures.
2. Subject has completed the 6-Month Treatment Period in pivotal study M12-671.
3. Subject must agree to use two forms of non-hormonal contraception (dual contraception) consistently during the Treatment and the Post-Treatment Follow-Up Periods (through Month 6).
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1.Il soggetto ha volontariamente firmato e datato il modulo di consenso informato (MCI), approvato da una Commissione di Revisione dell’Istituzione/Comitato Etico (IRB/CE), prima dell’inizio di qualsiasi procedura specifica dello studio.
2.Il soggetto ha completato il Periodo di trattamento di 6 mesi nello studio pivotal M12-671.
3.Il soggetto deve impegnarsi a utilizzare due forme di contraccettivi non ormonali (doppia contraccezione) costantemente durante il Periodo di trattamento e il Periodo di follow-up post-trattamento (fino al termine del Mese 6)
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E.4 | Principal exclusion criteria |
1. Pivotal study M12-671 Month 6 TVU or other diagnostic procedure shows clinically significant gynecological condition
2. Subject has BMD loss ≥ 8% in the spine, femoral neck or total hip as specified per the algorithm for Management of Bone Loss at Month 6 of the Treatment Period in pivotal Study M12-671.
3. Subject met criteria for removal from therapy in pivotal Study M12-671.
4. Subject plans to become pregnant in the next 18 months.
5. Subject will be unable or unwilling to comply with study-related assessments and procedures
6. Subject has a newly diagnosed or clinically significant medical condition that requires intervention OR an unstable medical condition that makes the subject an unsuitable candidate for the study in the opinion of the investigator. |
1.L’ecografia transvaginale (TVU) eseguita al Mese 6 dello studio pivotal M12-671 o un’altra procedura diagnostica evidenzia una patologia ginecologica clinicamente significativa.
2.Il soggetto ha una perdita di DMO 8% nella colonna vertebrale, nel collo del femore o nell’anca totale, specificata secondo l’algoritmo per la gestione della perdita ossea, al Mese 6 del Periodo di trattamento nello studio pivotal M12-671.
3.Il soggetto soddisfa i criteri per l’interruzione della terapia nello studio pivotal M12-671.
4.Il soggetto prevede di iniziare una gravidanza nei 18 mesi successivi.
5.A giudizio dello sperimentatore, il soggetto non è in grado o non è disposto ad attenersi alle valutazioni e alle procedure correlate allo studio, inclusi la compilazione del diario elettronico e l’uso costante della doppia contraccezione non ormonale per tutto il periodo richiesto.
6.Il soggetto ha una condizione medica di nuova diagnosi o clinicamente significativa che richiede intervento OPPURE una condizione medica instabile che rende il soggetto non idoneo allo studio, a giudizio dello sperimentatore
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of responders at each month based upon the mutually-exclusive scales for daily assessment of DYS and NMPP measured by the Daily Assessment of Endometriosis Pain (modified Biberoglu and Behrman [B&B] scales using the e-Diary); use of analgesic medication for endometriosis-associated pain will be included in the responder definition. |
Percentuale di responder a ciascun mese sulla base delle scale mutuamente escludibili per la valutazione giornaliera della DYS e dell’NMPP, misurate mediante la Valutazione giornaliera del dolore da endometriosi (scale di Biberoglu e Behrman [B&B] modificate, utilizzando il diario elettronico); l’uso di farmaci analgesici per il dolore associato all’endometriosi sarà incluso nella definizione di responder. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, Month 1-Month 6 in the treatment periood and Month 1-Month6 in the Post-Treatment Follow-Up Period. |
Giorno 1, Mese 1-Mese 6 nel periodo di trattamento e Mese 1-Mese 6 nel periodo di follow up post tratt |
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E.5.2 | Secondary end point(s) |
• Proportion of responders at each month for dyspareunia as assessed by the e-Diary.
• Change from baseline to each month in DYS, as assessed by the e-Diary.
• Change from baseline to each month in NMPP, as assessed by the e-Diary.
• Change from baseline to each month in dyspareunia, as assessed by the e-Diary.
• Change from baseline to each month in analgesic use to treat endometriosis-related pain, as assessed by the e-Diary.
• Results of Endometriosis Health Profile-30(EHP-30) domain of pain at each assessed visit.
• Results of EHP-30 domain of sexual relationship at each assessed visit
• Change from baseline to each assessed visit in Health Related Productivity Questionnaire (HRPQ) scores.
• Endometriosis related number of non-study health visits, number of days in hospital and type of procedures performed based on Health Resource Utilization Questionnaire (HRUQ).
• Change from baseline to each month in Numeric Rating Scale (NRS) scores, as assessed by the e-Diary.
• Response at each month to the Patient Global Impression of Change (PGIC) questionnaire.
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Percentuale di responder a ciascun mese per la dispareunia, valutata mediante il diario elettronico.
• Variazione dal basale a ciascun mese della DYS, valutata mediante il diario elettronico.
• Variazione dal basale a ciascun mese dell’NMPP, valutata mediante il diario elettronico.
• Variazione dal basale a ciascun mese della dispareunia, valutata mediante il diario elettronico.
• Variazione dal basale a ciascun mese dell’uso di analgesici per il trattamento del dolore da endometriosi, valutata mediante il diario elettronico.
• Risultati del questionario EHP-30 (Endometriosis Health Profile-30) per il fattore Dolore in ciascuna visita valutata.
• Risultati del questionario EHP-30 per il fattore Rapporto Sessuale in ciascuna visita valutata.
• Variazione dal basale a ciascuna visita valutata dei punteggi del questionario HRPQ (Health Related Productivity Questionnaire).
• Numero di visite mediche non di studio correlate all’endometriosi, numero di giorni di degenza ospedaliera e tipo di procedure eseguite sulla base del questionario HRUQ (Health Resource Utilization Questionnaire).
• Variazione dal basale a ciascun mese dei punteggi NRS (Numeric Rating Scale), valutata mediante il diario elettronico.
• Risposta a ciascun mese al questionario PGIC (Patient Global Impression of Change).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment Period until Month 6/PD. During the Post-Treatment Follow-Up Period, daily assessments will be recorded in the e Diary through Follow-Up Month 6. |
Periodo di trattamento fino al mese 6/Interruzione Anticipata. Durante il periodo di follow up Post- trattamento, le valutazioni giornaliere saranno registrate nel diario elettronico durate il Mese 6 di Follow up. |
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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 | Yes |
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 | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
due dosi di elagolix: 150 mg una volta al giorno e 200 mg due volte al giorno |
Two doses of elagolix: 150 mg daily, 200 mg twice a day |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 74 |
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 |
Italy |
Austria |
New Zealand |
Argentina |
Australia |
Brazil |
Czech Republic |
Hungary |
Spain |
Poland |
Russian Federation |
South Africa |
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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Last visit of the last subject |
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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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |