| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Pacientes con enfermedad avanzada y estreñimiento inducido por opiáceos
Opioid-induced constipation in subjects with advanced illness |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010774 |
| E.1.2 | Term | Constipation |
|
| 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 |
| Primary: The primary objective of this study is to evaluate the efficacy and safety of a fixed dose of SC methylnaltrexone in inducing laxation over a 7-day period in subjects with advanced illness and OIC. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary: The secondary objectives of this study are to assess the effect of SC methylnaltrexone on patient-reported constipation symptoms and constipation-related quality of life and to assess the efficacy of SC methylnaltrexone beyond 7 days in individuals with advanced illness and OIC. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
The subject:
1.Is a man or woman aged 18 years or older.
2.Has a diagnosis of advanced illness (ie, a terminal illness such as incurable cancer or other end-stage disease).
3.Has a life expectancy of ≥ 1 month.
4.Is able to give informed consent and to answer patient-reported outcomes (PRO) questions by himself or herself.
5.Is receiving opioids, both
a.On a regular schedule, not just as-needed (PRN) or rescue doses, for the control of pain for at least 2 weeks before the first dose of test article, and
b.On a stable opioid regimen for at least 3 days before the first dose of test article. “Stable” is defined as no reduction in dose of ≥50%. Increases to the opioid regimen are permitted.
6.Has a diagnosis of constipation, defined as either
a.Fewer than 3 bowel movements during the previous week by history, and no clinically notable laxation in the 24 hours before the first dose of test article, or
b.No clinically notable laxation in the 48 hours before the first dose of test article. Note: Small amounts of “leakage” of liquid stool or “pellets” may or may not be considered clinically notable, at the discretion of the investigator.
7.Has constipation further defined as opioid induced, as determined by the investigator.
8.Is on a stable laxative regimen for at least 3 days before the first dose of test article administration (eg, stool softener and senna or equivalent). This means that there must be a standing laxative order (not PRN).
a.A subject who meets inclusion criterion 6a and uses or used a rescue laxative (or enema/suppository) that produces a notable bowel movement within the 24 hours before the first dose of test article must wait to be laxation free for 24 hours in order to receive test article.
b.A subject who meets inclusion criterion 6b and receives or received a rescue laxative (or enema/suppository) that produces a notable bowel movement within the 24 hours before the first dose of test article must wait to be laxation free for 48 hours in order to receive test article.
Note: Rescue medications or rescue procedures for constipation may not be used within 4 hours before or 4 hours after test article administration.
9.Has stable vital signs, as determined by the investigator.
10.Has had an electrocardiogram (ECG) performed during the screening visit or within the 2 months before the screening visit. If an ECG is not performed specifically for this study, a copy of the previously recorded tracing must be obtained and stored in the source documents.
11.Has a negative urine pregnancy test result at screening (for women of presumed childbearing potential).
12.Must be surgically sterile, or must agree to use a medically acceptable method of birth control or practice sexual abstinence for the duration of the study and for 15 days after the last dose of test article (unless female and postmenopausal, ie, > 12 months since the last menstrual period). |
|
| E.4 | Principal exclusion criteria |
The subject:
1.Has received previous treatment with methylnaltrexone.
2.Has a known or suspected mechanical gastrointestinal obstruction.
3.Has any potential nonopioid cause of bowel dysfunction that in the opinion of the investigator might be a major contributor to the constipation.
4.Has current peritoneal catheter for intraperitoneal chemotherapy or dialysis.
5.Has clinically significant active diverticular disease as determined by the investigator.
6.Has evidence of fecal impaction either by physical examination or x-ray examination.
7.Has physical evidence of peritonitis.
8.Has a history of bowel surgery within 10 days before test article administration.
9.Has a fecal ostomy.
10.Has used vinca alkaloids (eg, vincristine, vinblastine, or vinorelbine) at any time during the 6 months before screening.
11.Has a body weight less than 38 kg.
12.Has a history of stage 4 or 5 chronic kidney disease (glomerular filtration rate [GFR] < 30 mL/min per 1.73 m2).
13.Has a known or suspected allergy to methylnaltrexone or other similar compounds (ie, naltrexone or naloxone).
14. Is participating or participated in studies involving investigational products within the 30 days before screening.
15.Is a woman who is pregnant and/or nursing.
16.Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of subjects who have a laxation response within 4 hours after at least 2 of the first 4 doses (the first week of treatment). |
|
| 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 | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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.8.3 |
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 | 100 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 20 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 20 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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