E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Opioid-induced constipation (OIC) |
Estreñimiento inducido por opioides (EIO) |
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E.1.1.1 | Medical condition in easily understood language |
Constipation after taking Opioid drugs |
Estreñimiento después de tomar medicamentos opioides |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010774 |
E.1.2 | Term | Constipation |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 study is to compare the efficacy of NKTR-118 12.5 and 25 mg with placebo in the treatment of patients who have OIC. |
Comparar la eficacia de NKTR-118 12,5 y 25 mg con placebo en el tratamiento de los pacientes con estreñimiento inducido por opioides (EIO). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare NKTR-118 12.5 and 25 mg with placebo on the daily signs and symptoms associated with OIC (straining, sensation of incomplete evacuation, and stool consistency), symptoms of constipation and quality of life. |
Comparar los efectos de NKTR-118 12,5 y 25 mg con placebo sobre los signos y síntomas diarios asociados a EIO (esfuerzo, sensación de evacuación incompleta y consistencia de las deposiciones), los síntomas de estreñimiento y la calidad de vida. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Provision of written informed consent prior to any study-specific procedures. Men and women who are between the ages of ?18 and <85 years. Self-reported active symptoms of OIC at screening (<3 SBMs/week and experiencing ?1 reported symptom of hard/lumpy stools, straining, or sensation of incomplete evacuation/anorectal obstruction in at least 25% of BMs over the previous 4 weeks); and Documented confirmed OIC (<3 SBMs/week on average over the 2-week OIC confirmation period. Receiving a stable maintenance opioid regimen consisting of a total daily dose of 30 mg to 1000 mg of oral morphine, or equianalgesic amount(s) of 1 or more other opiod therapies for a minimum of 4 weeks prior to screening for non-cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression. Willingness to stop all laxatives and other bowel regimens including prune juice and herbal products throughout the 2-week OIC confirmation period and the 12-week treatment period, and to use only bisacodyl as rescue medication if a BM has not occurred within at least 72 hours of the last recorded BM. |
Consentimiento informado por escrito antes de realizar ningún procedimiento específico del estudio Varones y mujeres con edades comprendidas entre 18 y < 85 años. Síntomas activos de EIO notificados por el paciente en la selección (< 3 DE/semana y presencia de 1 síntoma notificado de deposiciones duras/grumosas, esfuerzo o sensación de evacuación incompleta/obstrucción anorrectal en al menos el 25 % de las deposiciones durante las 4 semanas previas) y EIO confirmado documentado (< 3 DE/semana, por término medio, durante el período de confirmación del EIO de dos semanas. En tratamiento con un régimen de mantenimiento estable de opioides que consiste en una dosis diaria total de entre 30 y 1.000 mg de morfina oral o una cantidad equianalgésica de uno o más de otros tratamientos opioideos durante un mínimo de 4 semanas antes de la selección por dolor no oncológico sin cambios previstos en las necesidades de dosis de opioides durante el período previsto del estudio como consecuencia de progresión de la enfermedad. Disposición a suspender todos los regímenes laxantes e intestinales de otros tipos, incluidos los productos de herbolario y el zumo de ciruela durante el período de confirmación del EIO de dos semanas y el período de tratamiento de 12 semanas y a utilizar únicamente bisacodilo como medicación de rescate si no se ha hecho una deposición, como mínimo, en las 72 horas siguientes a la última deposición registrada. |
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E.4 | Principal exclusion criteria |
Patients receiving Opioid regimen for treatment of pain related to cancer. History of cancer within 5 years from first study visit with the exception of basal cell cancer and squamous cell skin cancer. Medical conditions and treatments associated with diarrhea, intermittent loose stools, or constipation. Other issues to the gastrointestinal tract that could impose a risk to the patient. Pregnancy or lactation. |
Pacientes en tratamiento con un régimen opioideo por dolor oncológico. Antecedentes de cáncer en los 5 años anteriores a la visita de selección a excepción de carcinoma basocelular y espinocelular de piel. Procesos médicos y tratamientos asociados a diarrea, deposiciones sueltas e intermitentes o estreñimiento. Otros problemas relacionados con el tubo digestivo que podrían suponer riesgos para el paciente. Embarazo o lactancia. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response (responder/non-responder) to study drug during Weeks 1 to 4, where a responder is defined as having at least 3 Spontaneous Bowel Movements (SBMs)/week, with at least 1 SBM/week increase over baseline, for at least 3 out of the first 4 weeks. |
Respuesta (paciente con respuesta/paciente sin respuesta) al fármaco del estudio durante las semanas 1 a 4, de modo que se define paciente con respuesta como aquel que presente al menos 3 DE/semana, con aumento de al menos 1 DE/semana con respecto al momento basal, durante al menos 3 de las 4 primeras semanas. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 4 weeks |
Hasta 4 semanas |
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E.5.2 | Secondary end point(s) |
Response (responder/non-responder) to study drug in the LIR subgroup during Weeks 1 to 4, where a responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline, for at least 3 out of the first 4 weeks.
Response (responder/non-responder) to study drug over the entire 12 week treatment period, where a responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline, for at least 75% of the weeks.
Regularity during the first 4 weeks of treatment, where regularity is measured as the mean number of days per week with at least 1 SBM during Weeks 1 to 4. |
Respuesta (paciente con respuesta/paciente sin respuesta) al fármaco del estudio en el subgrupo RIL durante las semanas 1 a 4, de modo que se define paciente con respuesta como aquel que presente al menos 3 DE/semana, con aumento de al menos 1 DE/semana con respecto al momento basal, durante al menos 3 de las 4 primeras semanas.
Respuesta (paciente con respuesta/paciente sin respuesta) al fármaco del estudio durante todo el período de tratamiento de 12 semanas, de modo que se define paciente con respuesta como aquel que presente al menos 3 DE/semana, con aumento de al menos 1 DE/semana con respecto al momento basal, durante al menos el 75 % de las semanas.
Regularidad durante las 4 primeras semanas de tratamiento, de modo que la regularidad se mide como el número medio de días por semana con al menos 1 DE durante las semanas 1 a 4. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 4 weeks 12 weeks Up to 4 weeks |
Hasta 4 semanas 12 semanas Hasta 4 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 | Yes |
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 | 3 |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Croatia |
Hungary |
Spain |
Sweden |
United Kingdom |
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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LVLS |
Última visita, último 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 |