E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Opioid-induced Bowel Dysfunction |
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MedDRA Classification |
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 identify at least one orally-dosed alvimopan treatment regimen that improves spontaneous bowel movement (SBM) frequency compared to placebo while maintaining an acceptable tolerability profile. |
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E.2.2 | Secondary objectives of the trial |
To further compare the efficacy, including durability of the efficacy response, among treatment regimens To demonstrate the lack of effect of the treatment regimens on opioid analgesia To further compare the safety among the treatment regimens To describe the steady-state population pharmacokinetics of alvimopan and its main metabolite when alvimopan is dosed orally either once or twice daily To quantify the disease burden of OBD via the SF-36 and PAC-QOL
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subject must be: Male or female 18 years or older at the time of the Screening Visit. Taking chronic opioid therapy for non-cancer related pain. The therapy must comprised of a full agonist opioid that is dosed chronically and administered orally, transdermally, intravenously, or subcutaneously, and dosed stably (+20% total daily dose and without any dose reductions) for at least one month prior to the Screening Visit at a minimum daily dose of at least 30 mg oral morphine equivalents Meet the protocol-definition of opioid-induced bowel dysfunction as follows: Since starting opioid therapy, a history based on subject recall of decreased BM frequency and at least one subjective BM symptoms (incomplete evacuation/hard stools/straining). To be randomized on Day 1 subjects must have a confirmed 2-week baseline history based on IVRS data of decreased BM frequency, occurrence of at least one of the subjective BM symptoms and compliance with the guidance for rescue laxative use. Female subjects must either be of non-child bearing potential, have a negative pregnancy test at screening and agree to use acceptable contraception throughout the study. Agree to all study procedure and sign and date the informed consent form.
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E.4 | Principal exclusion criteria |
Subject will not be eligible for inclusion if; Subject is pregnant or lactating, or planning to become pregnant during the study. Subject is not ambulatory (e.g., bed or wheel chair bound). Subject has participated in another trial with an investigational drug, device or procedure within 30 days prior to the Screening Visit. Subject has been randomized to investigational product in this study (SB-767905/011) at anytime in the past. Subject is unable to eat or drink. Subjects who are unable to take oral medications or to hold down oral medications due to vomiting are excluded. Subject is taking opioids for cancer-related pain or for the management of drug addiction. Subject is unable or unwilling to discontinue the use of and/or refrain from using laxatives of all types and formulation other at the Screening Visit and throughout the entire study. Should a laxative regimen be needed, GlaxoSmithKline will provide the subject with a rescue laxative (oral bisacodyl tablets) for rescue use only throughout the entire study. Subject has severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications of constipation. Subject with gastrointestinal or pelvic disorders known to affect bowel transit, produce GI obstruction, or contribute to bowel dysfunction. Subject, who in the investigators opinion, has bowel dysfunction that is predominantly resulting from causes other than the chronic use of opioids. Subject with chronic fecal incontinence. Subject, who in the investigators opinion, has an uncontrolled systemic disease that would contraindicate participation in this study. Subject has current evidence of, or has been treated for a malignancy within the past five years Subject has clinically significant laboratory abnormalities prior to Randomization Subject has a history of alcohol and/or substance abuse within the past 2 years. Subject is taking opioids that are mixed agonists/antagonists or partial agonists Subject has any other known condition or physical examination finding prior to Randomization, which could contraindicate participation in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the changes in weekly spontaneous bowel movement frequency during the first 3 weeks of the 6-week Treatment Period |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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The end of trial will be the 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 | 5 |
E.8.9.1 | In the Member State concerned days | |
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 |