E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Opioid-induced Constipation in Subjects with Non-malignant Chronic Pain Receiving Opioid Therapy |
estreñimiento inducido por opiáceos en pacientes con dolor crónico de origen no oncológico que están recibiendo tratamiento con opiáceos. |
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E.1.1.1 | Medical condition in easily understood language |
Opioid-induced Constipation |
estreñimiento inducido por opiáceos |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071128 |
E.1.2 | Term | Opioid induced constipation |
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 |
To evaluate the efficacy of naldemedine compared to placebo without concomitant laxative treatment in subjects with non-malignant chronic pain receiving a stable opioid regimen for ?1 month and having OIC |
Evaluar la eficacia de la naldemedina, en comparación con el placebo y en ausencia de un tratamiento laxante concomitante, en pacientes con dolor crónico de origen no oncológico, que estén recibiendo un tratamiento estable con opiáceos durante ? 1 mes y padezcan estreñimiento inducido por opiáceos (EIO). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of naldemedine on the frequency of Spontaneous Bowel Movements (SBMs) and SBMs without straining. To evaluate the safety and tolerability of naldemedine |
Evaluar la eficacia de la naldemedina en la frecuencia de las deposiciones espontáneas (DE) y las DE sin tenesmo.
Evaluar la seguridad y la tolerabilidad de la naldemedina. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects aged 18 to 80 years inclusive at the time of informed consent 2. Subjects must have non-malignant chronic pain treated with opioids for at least 3 months and must have OIC 3. Subjects must be treated with a stable opioid regimen at a total daily dose on average of ? 30 mg equivalents of oral morphine sulfate for at least 1 month prior to Screening 4. Subjects must not be currently using laxatives or must be willing to discontinue laxative use at Screening and must be willing to use only the rescue laxatives provided throughout the study duration 5. Subjects must meet criteria based on the Bowel Movement and Constipation Assessment (BMCA) Diary |
1. Pacientes con edades comprendidas entre 18 y 80 años hasta el momento del consentimiento informado. 2. Los pacientes deben padecer dolor crónico de origen no oncológico, tratado con opiáceos durante un mínimo de 3 meses, además de EIO. 3. Los pacientes deben estar en tratamiento estable con opiáceos, con una dosis diaria total media ? 30 mg de equivalentes al sulfato de morfina, durante un mínimo de 1 mes antes del screening. 4. Los pacientes no deberán estar usando laxantes o deben estar dispuestos a interrumpir el uso de laxantes en el momento del screening y deben estar dispuestos a usar únicamente los laxantes de rescate que se entreguen durante la duración del estudio. 5. Los pacientes deben cumplir los criterios basados en el diario de evaluación de las deposiciones y el estreñimiento (Bowel Movement and Constipation Assessment, BMCA) |
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E.4 | Principal exclusion criteria |
1. Evidence of significant structural abnormalities of the gastrointestinal tract (GI) 2. Evidence of active medical diseases affecting bowel transit 3. History or presence of pelvic disorders that may be a cause of constipation 4. Surgery (except for minor procedures) within 60 days of Screening 5. History of chronic constipation prior to starting analgesic medication or any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation (e.g., mechanical gastrointestinal obstruction) 6. Subjects who have never taken laxatives for the treatment of OIC 7. History of active treatment for cancer within the last 2 years (except for basal cell or squamous cell carcinoma of the skin that have been successfully resected) or tamoxifen [Nolvadex®] and raloxifene [Evista®] when being used for prevention of breast cancer |
1. Hechos indicativos de anomalías estructurales importantes del tubo digestivo (TD). 2. Pruebas de enfermedades activas que afecten al tránsito intestinal, 3. Antecedentes o presencia de alteraciones pélvicas que puedan ser las causantes del estreñimiento. 4. Haber sido sometido a una intervención quirúrgica (excepto las intervenciones menores) en los 60 días previos al screening 5. Antecedentes de estreñimiento crónico antes del comienzo del tratamiento farmacológico analgésico o cualquier posible causa de enteropatía que no se deba a los opiáceos y que pudiera ser una causa principal del estreñimiento (p. ej., obstrucción intestinal mecánica). 6. Pacientes que nunca hayan tomado laxantes para el tratamiento del EIO. 7. 9. Antecedentes de tratamiento oncológico activo en los últimos 2 años (a excepción del carcinoma basocelular o espinocelular de la piel que haya sido reseccionado satisfactoriamente) o tratamiento con tamoxifeno (Nolvadex®) y raloxifeno (Evista®) como tratamiento preventivo del cáncer de mama. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the proportion of responders. A positive response week will be defined as ? 3 SBMs per week and an increase from baseline of ? 1 SBM per week for that week. Any number of SBMs rated on the Bristol Stool Scale as 1 within a 2 hour period will be counted as a single SBM. |
El criterio de valoración principal de la eficacia será el porcentaje de pacientes que respondan al tratamiento. Una semana con respuesta positiva se define como ? 3 DE a la semana y un aumento de ? 1 DE por semana en esa semana desde el inicio. Cualquier número de DE puntuadas en la Escala de Bristol (escala de valoración de las características de las heces) con un 1 en un período de 2 horas se contabilizará como una sola DE. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1- Mean change in the frequency of SBMs per week from baseline to the first four weeks of the Treatment Period 2- Mean change in the frequency of SBMs per week without straining from baseline to the last two weeks of the Treatment Period 3- Mean change in the frequency of SBMs per week from baseline to each two weeks of the Treatment Period |
? Variación media de la frecuencia de DE por semana, desde el inicio hasta las primeras cuatro semanas del período de tratamiento. ? Variación media de la frecuencia de DE por semana, en ausencia de tenesmo, desde el inicio hasta las últimas dos semanas del período de tratamiento. ? Variación media de la frecuencia de DE por semana, desde el inicio hasta cada una de las dos semanas del período de tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Week 4 2- Last two weeks of the Treatment Period 3- Every two weeks |
1- semana 4 2- las ultimas dos semanas del periodo de tratamiento 3- cada dos semanas |
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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) | 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 | 3 |
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 | 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 |
Germany |
Austria |
Poland |
Czech Republic |
Spain |
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 Last Subject (LVLS) |
Ultima visita del ultimo paciente. |
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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |