E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose Ranging Study to Evaluate the Efficacy and Safety of 2 Dose Regimens of Intravenous TAK-954 for the Prophylaxis and Treatment of Postoperative Gastrointestinal Dysfunction in |
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E.1.1.1 | Medical condition in easily understood language |
To determine the IMP decreases the duration of gastrointestinal (GI) dysfunction in patients undergoing major abdominal or laparoscopic-assisted surgeries that involve bowel manipulation. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10076042 |
E.1.2 | Term | Feeding intolerance |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
To assess the efficacy and safety of intravenous (IV) TAK-954 for accelerating the recovery of GI function postsurgery in patients undergoing open or laparoscopic-assisted partial small- or large-bowel resection. |
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E.2.2 | Secondary objectives of the trial |
To determine efficacy and safety of preoperative dosing of IV TAK-954 relative to preoperative and postoperative regimens of IV TAK-954 for accelerating the recovery of GI function postsurgery. To determine the relative safety and efficacy of 0.1 mg and 0.5 mg IV TAK-954 given preoperatively and postoperatively for up to 10 days or resolution of GI dysfunction postsurgery for accelerating the recovery of GI function postsurgery. To determine the pharmacokinetics (PK) of TAK-954 in patients undergoing major abdominal surgery.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria before entry into the study: The subject is male or female (and not pregnant) and is at least 18 years old. The subject is scheduled to undergo a laparoscopic-assisted, or open partial small- or large-bowel, resection. A female subject of childbearing potential willing and agreeable to use highly effective contraception or sexual abstinence during the course of the study and up to 30-days posttreatment. |
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E.4 | Principal exclusion criteria |
Any subject who meets any of the following criteria will not qualify for entry into the study: Has significant mechanical bowel obstruction that is not expected to resolve after the surgery, short bowel syndrome, pre-existing clinically significant GI motility disorder (eg, gastroparesis, scleroderma, chronic intestinal pseudo-obstruction), uncontrolled diabetes (glycosylated hemoglobin [HbA1c] >10%), has an active gastric pacemaker, or requires parenteral nutrition. Previous major abdominal surgery (eg, gastrectomy, gastric bypass, gastric sleeve, lap banding, Whipple, pancreatic resection, total/subtotal colectomy, hemicolectomy, extensive bowel resection). History of radiation therapy to the abdomen or pelvis. Scheduled to undergo any of the following surgeries: low anterior resection, total or subtotal colectomy,colostomy, ileostomy or reversal of stoma. Has pre-existing hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe;total score 10 to 15 points). Has alanine aminotransferase (ALT) >3×upper limit of normal (ULN). Has an estimated glomerular filtration rate <30 mL/min. Has received alvimopan, erythromycin, prucalopride, metoclopramide, domperidone, or azithromycin in the 24 hours prior to surgery or during the study period. Has a resting heart rate of < 50 beats per minute (bpm). Has clinically significant electrocardiogram (ECG) abnormalities indicative of acute cardiac instability, as determined by the investigator at screening; more than first degree atrioventricular (AV) block; >5 beats of non-sustained ventricular tachycardia (VT) at a rate >120 bpm); ECG changes consistent with acute myocardial ischemia or infarction. Has the QT interval with Fridericia correction method (QTcF) interval ≥450 msec or other factors that increase the risk of QT prolongation or arrhythmic events at screening. The records of subjects with bundle branch block and a prolonged QTcF should be reviewed by a medically qualified person in consultation with the medical monitor and the sponsor for potential inclusion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is time to resolution of upper and lower GI function (eg, time to tolerance of solid food [no vomiting or no clinically significant nausea for 1 day after the first solid meal] and first spontaneous bowel movement, whichever occurs later) postsurgery. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints for this study are: Time from the end of the surgery (time the incision is closed) until ready for discharge (defined as the time until the subject presents effective intestinal transit [spontaneous bowel movement], tolerates solids without vomiting or clinically significant nausea for 1 day after the first solid meal, has satisfactory pain control with oral analgesics, and is medically stable/free of complications). Time from the end of surgery until discharge orders are written. Time from the end of the surgery to discharge from hospital. Time from end of surgery to tolerance of first solid food, defined as intake of solids without vomiting or clinically significant nausea for 1 day after the first solid meal. Time from end of surgery to first spontaneous bowel movement, defined as a stool not induced by the use of enemas or laxatives. Percent of subjects with POGD ≥5 days defined as subjects unable to tolerate solid foods, take anything by mouth, or requiring insertion or reinsertion of NG at or after 5 days postsurgery. Percentage of subjects requiring insertion of NG tube postsurgery, for drainage and symptom relief in case of persistent nausea and vomiting postsurgery. Time from end of surgery to first flatus. Observed concentration of TAK-954 at the end of infusion on Day 1. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | Yes |
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) | 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.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | No |
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 |
Belgium |
Germany |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 overall study ends when the last subject completes the last planned or follow-up visit/interaction associated with a planned visit (this can be a phone contact), discontinues from the study, or is lost to follow-up (ie, the investigator is unable to contact the 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 | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 12 |