E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post operative ileus (POI)in subjects who have undergone repair of large (³10 cm) ventral hernias . This study will examine the effect of IV MOA-728 versus placebo in shortening the time to return of bowel function in subjects receiving opioid analgesia administered via PCA, who have undergone repair of large (³10 cm) ventral hernias with or without a mesh prosthesis via laparotomy or laparoscopy. |
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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 | 10054048 |
E.1.2 | Term | Postoperative ileus |
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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 assess the efficacy of IV MOA-728 in subjects who have undergone repair of large (³10 cm) ventral hernias, with or without a mesh prosthesis via laparotomy or laparoscopy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are 1) to assess the safety of IV MOA-728 administered every 6 hours in these postsurgical subjects and 2) to examine clinically meaningful events for nausea or retching/vomiting at 24 hours as evaluated by the Opioid Related Symptom Distress Scale (SDS) instrument. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Subjects must sign and date an ICF. 2.Male and female subjects ³18 years of age. 3.Subjects must meet the American Society of Anesthesiologists (ASA) physical status I, II, or III. 4.Subjects must be scheduled for repair of a large (estimated to be at least ³10 cm) ventral hernia with or without mesh prosthesis via laparotomy or laparoscopy with general anesthesia. 5.Subjects must have an anticipated length of hospital stay of at least 3 days. 6.Subjects with a history of inflammatory bowel disease are eligible as long as the disease is not currently active and all other criteria are met. 7.Women of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine or serum pregnancy test before surgery and must agree and commit to the use of a reliable method of birth control for the duration of the study and for 15 days after the last dose of test article. Appropriate forms of birth control are abstinence; oral, implantable, or injectable contraceptives; spermicide in conjunction with a barrier such as a condom or diaphragm; and intrauterine device. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Men who are sexually active must agree and commit to the use of a medically acceptable form of contraception during the study and for 15 days after the last dose of test article. 8.Body weight within the range of 40 to 150 kg (88 to 330 lb). |
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E.4 | Principal exclusion criteria |
1.Subjects with known hypersensitivity to methylnaltrexone, naltrexone, or naloxone. 2.Subjects who received any investigational new drug or procedure (experimental) within 30 days before randomization. 3.Subjects with a recent history of treatment with vinca alkaloids (£6 months before randomization). 4.Subjects undergoing operations that include a planned bowel resection or colostomy. 5.Subjects with clinically important laboratory abnormalities or a significant medical and/or psychiatric history and comorbidities that would make participation in an investigational study inappropriate or make them high-risk for any surgical procedures. 6.Subjects whose medical history requires use of postoperative nonsteroidal anti-inflammatory drugs (NSAIDs). 7.Subjects taking tricyclic antidepressants. 8.Subjects with corrected QT (QTc) interval greater than 500 ms based on the 12-lead screening electrocardiogram (ECG). 9.Subjects with a history of alcohol abuse or prescription or nonprescription drug abuse within the past 2 years. 10.Subjects with a history of chronic constipation. 11.Known history of chronic active hepatitis B, hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection. 12.Women who are lactating. 13.Subjects with a calculated creatinine clearance (Cockcroft-Gault GFR) £50 mL/min. Postoperative Requirements for Continuation (Only subjects who meet these criteria are to be randomly assigned): 1.Subjects must have stable vital signs (clinical judgment of the investigator). 2.Subjects surgical repair must have been either ³10 cm measured from edge to edge in its greatest dimension or multiple single defects that together measure ³10 cm edge to edge. Acceptable types of ventral hernia repair include primary repair, separation of components, repair of multiple single defects, and peristomal hernia repair. 3.Subjects must be receiving, or ordered to receive, IV opioids via PCA withmorphine, hydromorphone, or fentanyl for postoperative pain elief. Subjects must have access to PCA treatment for at least 24 hours after the end of surgery. 4.Subjects must not have any intraoperative findings, unanticipated surgical procedures (to include incarcerated bowel with compromised perfusion, bowel resection, ileosotmy, or colostomy) or complications of surgical procedure (clinical judgment of the investigator) that would make participation in the study inappropriate. 5.Nasogastric (NG)/orogastric (OG) tube must be removed. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the time to first bowel movement after the end of surgery (defined as the time when the last suture or staple is placed in the subject). |
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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 | 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 | 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.8.3 |
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.8.6 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 | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 1 |