E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post Operative ileus (POI) in patients who have had a segmental colectomy via open laparotomy. |
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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 test the following hypothesis:
In patients who have undergone segmental colectomy, the time between the end of surgery and first bowel movement is significantly shorter in the MNTX regimen than the equivalent assessment using a placebo regimen. |
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E.2.2 | Secondary objectives of the trial |
1. To assess the safety of IV MNTX administered every six hours in these post-surgical patients.
2. Tos assess the effects of IV MNTX on time to discharge eligibility and time to hospital discharge.
3. To examine frequency and bothersomeness of nausea and vomiting as assessed by the SDS instrument.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects > 18 years of age.
2. Patients must meet the American Society of Anesthesiologists (ASA) physical status I, II, or III.
3. Subjects must be scheduled for a segmental colectomy via open laparotomy with general anesthesia. Acceptable procedures include: partial colectomy, colectomy (right or left), transverse colectomy, hemicolectomy (right or left), sigmoidectomy, cecectomy, anterior proctosigmoidectomy and low anterior proctosigmoidectomy. All patients must have a primary anastomosis.
4. Patients with a history of inflammatory bowel disease are eligible as long as the disease is not currently active and all other criteria are met.
5. Negative for history of chronic active hepatitis B, HCV or HIV infection.
6. Patients must sign an ICF.
7. Females of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test prior to surgery and must use appropriate forms of birth control (oral, implantable or injectable contraceptives; spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine device or (IUD), throughout the study.
8. Body weight within range of 40 kg to 150 kg (88 to 330 lbs.) |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if the meet any of the following exclusion criteria: 1. Patients who are scheduled for laparoscopic surgery for the segmental colectomy.
2. Patients with known hypersensitivity to methylnaltrexone, naltrexone, or naloxone.
3. Patients who received any investigational new drug (experimental) in the 30 days prior to screening visit.
4. Patients with clinical evidence of radiation enteritis.
5. Patients with recent history of treatment with Vinca alkaloids (< 6 months).
6. Patients with history of ulcerative colitis.
7. Patients undergoing operations resulting in gastrointestinal ostomies.
8. Patients with a significant medical and/or psychiatric history and co-morbidities that would make participation in an investigational study inappropriate or make them high-risk for any surgical procedures.
9. Patients with stage IV malignancies or ASA status IV are excluded.
10. Patients with a prior history of total colectomy, small bowel obstruction, known or suspected bowel adhesions (other than minor, clinically non-significant adhesions), or endometriosis of the bowel.
11. Patients who are anticipated to use post-operative non-steroidal anti-inflammatories (NSAIDs) prior to the primary endpoint being met.
12. Patients taking tricyclic antidepressants.
13. Patients with QTc interval greater than 500ms based on the 12-lead screening electrocardiogram (ECG).
14. Patients with a history of alcoholic or prescription or non-prescription drug abuse within the past two years.
15. Females who are pregnant or lactating.
16. Patients with calculated creatinine clearance (Cockcroft-Gault GRF) <50ml/min.
Pre-operative Period
Within 24 hours of the planned segmental colectomy, Investigators or designees will review inclusion/exclusion criteria, obtain vital sign measurements including body weight, review concomitant medications, obtain a urine pregnancy test (within 72 hours of dosing) for women of childbearing potential, clinical laboratory tests, and a 12-lead ECG recording. Patients who continue to meet all inclusion/exclusion criteria within 24 hours of surgery will be allowed to continue in the study. Patients who no longer qualify will be discontinued and managed at the discretion of the attending physician.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time for the first bowel mevement from the end of surgery, defined as the time the last staple or suture is placed. |
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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 | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 | 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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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 | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |