E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Scientific Terminology Opioid-Induced Constipation (OIC) Laymen Terminology Constipation after taking Opioid drugs |
Terminología Científica Estreñimiento inducido por opioides (EIO) Terminología Laica Estreñimiento después de tomar medicamentos opioides |
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E.1.1.1 | Medical condition in easily understood language |
Cancer-Related Pain, Opioid-Induced Constipation |
Dolor oncológico, Estreñimiento inducido por opioides |
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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 | 14.0 |
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 mg and 25 mg with placebo in the treatment of opioid-induced constipation (OIC) in pain related to malignancy. |
El objetivo principal de este estudio es comparar la eficacia de NKTR-118 12,5 mg y 25 mg con respecto a un placebo para el tratamiento del estreñimiento inducido por opioides (EIO) en el dolor relacionado con el cáncer. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to compare NKTR-118 12.5 mg and 25 mg with placebo in the daily signs and symptoms associated with OIC (degree of straining, sensation of incomplete evacuation, and stool consistency), symptoms of constipation, and overall quality of life. |
El objetivo secundario es comparar los efectos de NKTR-118 12,5 mg y 25 mg con respecto a un placebo sobre los signos y síntomas diarios asociados al EIO (grado de esfuerzo, sensación de evacuación incompleta y consistencia de las heces), los síntomas del estreñimiento y la calidad de vida general |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Research version 1.0 24March2011
AstraZeneca intends to perform genetic research in the NKTR-118 clinical development programme to explore how genetic variations may affect the clinical parameters associated with NKTR-118
GENETIC RESEARCH OBJECTIVES: The objective of this research is to collect and store DNA for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability and efficacy) and/or susceptibility to Opioid-Induced Constipation (OIC) and/or agents used in combination and/or as comparators. |
INVESTIGACIÓN GENÉTICA version 1.0 24Marzo2011 AstraZeneca pretende realizar una investigación genética en el programa de desarrollo clínico de NKTR-118 para estudiar el modo en que las variaciones genéticas pueden afectar a los parámetros clínicos asociados a NKTR-118.
OBJETIVOS DE LA INVESTIGACIÓN GENÉTICA El objetivo de esta investigación consiste en recoger y conservar ADN para futuras investigaciones exploratorias sobre los genes y la variación genética que podrían influir en la respuesta (es decir, distribución, seguridad, tolerabilidad y eficacia) a NKTR-118 o a los fármacos utilizados en combinación o como productos de comparación o en la predisposición al EIO. |
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E.3 | Principal inclusion criteria |
1. Provision of written informed consent prior to any study-specific procedures.
2. Men and women aged 18 or older.
3. Histologically or cytologically confirmed neoplasm causing pain and requiring management with opioids.
4. Self-reported active symptoms of OIC at screening (<3 RFBMs/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 RFBMs/week on average aver the 2-week OIC confirmation period.
5. Receiving a stable maintenance opioid regimen consisting of a total daily dose of >30 mg of oral morphine, or equianalgesic amount(s) of 1 or more opioid therapies for a minimum of 4 weeks prior to screening for cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression. |
1. Entrega de un consentimiento informado por escrito antes del inicio de cualquiera de los procedimientos relacionados con el estudio. 2. Varones y mujeres de 18 años o más. 3. Neoplasia confirmada por histología o citología que cause dolor y precise tratamiento con opioides.
4. Síntomas activos de EIO notificados por el paciente en la selección (< 3 DSMR/semana y presencia de ? 1 síntoma notificado de deposiciones duras/en bolas, 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 DSMR/semana por término medio durante el periodo de confirmación del EIO de dos semanas).
5. En tratamiento con un régimen de mantenimiento estable de opioides que consista en una dosis diaria total ? 30 mg de morfina oral o cantidad equianalgésica de uno o más de otros tratamientos opioideos (véase el apéndice H) durante un mínimo de 4 semanas antes de la selección por dolor oncológico, sin que se anticipe una variación de las necesidades de dosis de opioides como consecuencia de la progresión de la enfermedad durante el periodo previsto de tratamiento de 4 semanas. |
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E.4 | Principal exclusion criteria |
1. Patients receiving Opioid regimen for treatment of pain other than related to cancer.
2. Any condition that may have affected the permeability of the blood-brain barrier, eg, known brain metastases, meningeal metastases, brain injury, multiple sclerosis, recent brain injury, uncontrolled epilepsy. 3. Patients with cancer-related pain due to ovarian cancer, leukaemia, or lymphoma are excluded. Patients with multiple myeloma will be allowed. 4. Patients requiring radiation therapy between the diaphragm and pelvis 4 weeks prior to Visit 1 (screening) and/or during the study are excluded. Any patients with suspected clinically relevant radiation-induced injury of small or large intestine are excluded. 5. Pregnancy or lactation. |
1. Pacientes que reciban un régimen opioideo para el tratamiento del dolor no oncológico. 2. Cualquier trastorno que pueda haber afectado a la permeabilidad de la barrera hematoencefálica, por ejemplo, metástasis cerebrales conocidas, metástasis meníngeas, lesión cerebral, esclerosis múltiple, lesión cerebral reciente, epilepsia no controlada. 3. Se excluirá a los pacientes con dolor oncológico por cáncer de ovario, leucemia o linfoma. Podrán participar los pacientes con mieloma múltiple.
4. Se excluirá a los pacientes que necesiten radioterapia entre el diafragma y pelvis 4 semanas antes de la visita 1 (selección) y/o durante el estudio. Quedan excluidos los pacientes con sospecha de lesión del intestino delgado o grueso inducida por la radiación con importancia clínica. 5. 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, where a responder is defined as having at least 3 Rescue-free bowel movements (RFBMs) per week during the 4-week treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks. |
Respuesta (paciente con respuesta/paciente sin respuesta) al fármaco del estudio durante el periodo de tratamiento de 4 semanas, definiéndose paciente con respuesta como aquel que presenta al menos 3 DSMR/semana, con aumento de al menos 1 DSMR/semana con respecto al momento basal, durante al menos 3 de las 4 semanas |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Will be collected daily through the 4-week treatment period. |
Se recogerán todos los días durante el período de tratamiento de 4 semanas |
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E.5.2 | Secondary end point(s) |
Change from baseline in RFBMs/week during the 4-week treatment period.
Regularity during the 4-week treatment period, where regularity is measured as the mean number of days per week with at least 1 RFBM.
Time (in hours) to first post-dose RFBM.
Change from baseline in the degree of straining associated with RFBMs during the 4-week treatment period.
Change from baseline in stool consistency (BSS) during the 4-week treatment period.
Percentage of days with complete evacuation during the 4-week treatment period.
Change from baseline in Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) total score and each domain score for Weeks 2 and 4. |
Variación con respecto al valor basal durante el periodo de tratamiento de 4 semanas.
Regularidad durante el periodo de tratamiento de 4 semanas, de forma que la regularidad se mide como el número medio de días por semana con al menos 1 DSMR
Tiempo (horas) hasta la primera DSMR
Variación con respecto al momento basal del grado de esfuerzo durante el periodo de tratamiento de 4 semanas.
Variación con respecto al momento basal de la consistencia media de las deposiciones (BSS) durante el periodo de tratamiento de 4 semanas.
Porcentaje de días con evacuación completa durante el periodo de tratamiento de 4 semanas.
Variación de la puntuación total y la puntuación de cada dominio de la escala PAC-SYM, y de la puntuación total y la puntuación de cada dominio de la escala PAC-QOL, entre el momento basal y las semanas 2 y 4. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Will be collected daily through the 4-week treatment period.
Will be evaluated at Visits 3, 5 and 6. |
Se recogerán todos los días durante el período de tratamiento de 4 semanas
Serán evaluados en las visitas 3, 5 y 6. |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 |
Bulgaria |
Croatia |
Czech Republic |
Germany |
Hungary |
Poland |
Romania |
Slovakia |
South Africa |
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 of the last subject |
Última visita del 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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |