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 compare the safety among the treatment regimens, while offering continued access to blinded investigational product to subjects who have completed a prior GSK alvimopan OBD study in cancer pain subjects. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the lack of effect of the treatment regimens on opioid analgesia To compare OBD global improvement To compare treatment satisfaction To compare maintenance stool softener and rescue laxative use 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 PAC-QOL
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Those who have completed a GSK alvimopan OBD study in cancer pain subjects (e.g., study SB-767905/008). 2. Taking chronic opioid therapy for cancer pain (note: permanent discontinuation of chronic opioid therapy during the study requires that the subject be discontinued from the study). The opioid therapy must meet the following conditions: - comprised of a full agonist opioid - administered orally, transdermally, intravenously, or subcutaneously - dosed chronically for at least one month prior to the Screening Visit at a minimum daily dose of at least 30 mg oral morphine equivalents 3. Those who met the protocol-defined criteria for having OBD in the original study and, who in the investigator’s opinion, continues to require therapy or management of OBD. 4. Those who understand the procedures, agrees to participate in the study, and has signed and dated the informed consent form prior to the initiation of any study-related activities, including discontinuation of pre-study laxative regimen or other prohibited medications. Given the likely clinical progression due to cancer and limited life expectancy for many of these subjects, there is no requirement that the subject’s consent implies participation for the entire duration of the Treatment Period. 5. Capable of completing the paper questionnaires. 6. If female , then the subject is currently either of: a) non-childbearing potential b) child-bearing potential, has a negative B-hCG pregnancy test (either urine or serum) at the Screening Visit (prior to investigational product), and agrees to use acceptable contraception throughout the study.
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating, or planning to become pregnant during the study. 2. Have participated in another trial with an investigational drug, device or procedure within 30 days prior to the Screening Visit, with the exception of another GSK alvimopan OBD studies in cancer pain subjects. Subject has been assigned to investigational product in this study (ABD101684) at anytime in the past. 3. Unable to eat or drink. Subjects who are unable to take oral medications or to hold down oral medications due to vomiting are excluded. 4. Taking opioids for the management of drug addiction. 5. Taking opioids that are mixed agonists/antagonists or partial agonists. 6. Unable or unwilling to discontinue the use of and/or refrain from using stool softeners and laxatives of all types and formulation (i.e., hyperosmotics, mineral oil, saline, stimulants, suppositories, lubricants, enemas, or any other natural products that promote bowel motility/cleansing) at the Treatment Assignment Visit and throughout the entire study. NOTE - Should a laxative regimen be needed, GlaxoSmithKline will provide the subject with a standardized maintenance stool softener and rescue laxative for use throughout the study. 7. Has severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications. 8. Have GI or pelvic disorders known to affect bowel transit, produce GI obstruction, or contribute to bowel dysfunction 9. Currently taking vinca alkaloids or plans to take vinca alkaloids during the study. Subject who has experienced paralytic ileus or intestinal pseudoobstruction associated with past chemotherapy treatment 10. In the investigator’s opinion, has bowel dysfunction that is predominantly resulting from causes other than the chronic use of opioids 11. Have chronic fecal incontinence. 12. Taking antidiarrheals (e.g., loperamide), has an incidence of diarrhea or loose stools in the 2 weeks prior to the Screening Visit or a history of intermittent diarrhea, loose stools or irritable bowel syndrome (IBS) symptoms which are consistent with the Rome II Criteria. 13. Have active viral hepatitis (any subtype including ongoing chronic hepatitis B) or has ever been infected with hepatitis C. 14. Have undergone prior radiation therapy that resulted in documented chronic radiation enteritis or radiation stricture, has undergone abdominal radiation therapy in the 2 weeks prior to the Screening Visit, is currently undergoing abdominal radiation therapy and/or plans to undergo abdominal radiation therapy during the study. 15. Have clinically significant laboratory abnormalities prior to Treatment Assignment suggestive of of primary hepatic dysfunction or active viral hepatitis, renal impairment andany other condition that would contraindicate participation in this study 16. Have a history of alcohol and/or substance abuse within the past 2 years. 17. Taking a concomitant medication or has any other known condition or physical examination finding prior to Treatment Assignment, which could contraindicate participation in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of reported adverse events, including serious adverse events. |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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 the 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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |