This study is to understand if TAK-954 can improve the daily nutritional intake of enteral feed that can be administered in patients who have become intolerant to enteral feeding.
- Conditions
- A Phase 2b, Randomized, Multi-Center, Double-Blind, Dose-Ranging Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous TAK-954 in Critically Ill Patients With Enteral Feeding IntoleranceTAK-954 in Critically Ill Patients With Enteral Feeding IntoleranceMedDRA version: 20.0Level: LLTClassification code 10074293Term: Enteral feeding intoleranceSystem Organ Class: 100000004861Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]
- Registration Number
- EUCTR2017-003206-41-GB
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
1. In the opinion of the investigator, the participant, or the participant’s legally acceptable representative (LAR), is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant’s LAR, signs and dates a written, informed consent form and any required privacy authorisation before the initiation of any study procedures.
3. The participant is male or female (and not pregnant) and is at least 18 years old.
4. The participant has at least a size 12-Fr nasogastric or orogastric tube with its tip at least 10 cm below the oesophagogastric junction confirmed radiologically (the tip of the tube must be in the body or the antrum of the stomach and not in the fundus).
5. The participant is intubated and mechanically ventilated in the ICU.
6. The participant is expected to remain alive, mechanically ventilated, and receive continuous enteral feeding for =48 hours following randomisation.
7. Have EFI, defined as a single GRV measurement of =250 mL with vomiting/retching within the last 24 hours, or a single GRV measurement of =500 mL with or without vomiting/retching within the last 24 hours.
8. A female participant 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 post treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1. Has received any investigational compound within 30 days before Screening.
2. Has received TAK-954 in a previous clinical study or as a therapeutic agent.
3. Has an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
4. Is under consideration for withdrawal of life-sustaining treatments within the next 72 hours.
5. Has had major esophageal or gastric surgery or direct luminal trauma on this admission (participants with lower abdominal surgery are not excluded unless enteral feeding is contraindicated).
6. Has mechanical bowel obstruction, short bowel syndrome, or the presence of an active gastric pacemaker.
7. Have 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).
8. Has alanine aminotransferase (ALT) >8×upper limit of normal (ULN).
9. Has an estimated glomerular filtration rate (GFR) <30 mL/min.
10. Is required to take excluded medications listed in the Protocol, Section 7.3.
11. Has been admitted primarily for treatment of a drug overdose.
12. Has a presence of a post-pyloric tube in place at Randomisation that may be used for EN.
13. Is receiving PN at Screening.
14. Is in diabetic ketoacidosis or non-ketotic hyperosmolar coma.
15. Has clinically significant ECG abnormalities indicative of acute cardiac instability, as determined by the investigator at Screening; more than first degree AV block; >5 beats of non-sustained ventricular tachycardia (VT) at a rate >120 bpm; ECG changes consistent with acute myocardial ischemia or infarction.
Note: Controlled atrial fibrillation (AF) or supraventricular tachycardia (SVT) is allowed with heart rate under 100 bpm at baseline.
16. Has QTcF interval =450 msec or other factors that increase the risk of QT prolongation or arrhythmic events at Screening. Participants with bundle branch block and a prolonged QTcF should be reviewed by a cardiologist for potential inclusion.
17. Has a different nutrient requirement than allowed in feeding protocol.(outside a range of 1.2 to 2 g/kg/day of proteins and up to 1.5 kcal/mL)
18. Have received erythromycin or metoclopramide in the previous 24 hours before Screening; domperidone or azythromycin in the previous 72 hours, or need ongoing macrolide antibiotics. Patients on chronic treatment with metoclopramide or that have received continuous treatment (=7 days) with metoclopramide during this hospital stay should be excluded.
19. Is in the opinion of the treating physician not eligible for treatment with metoclopramide.
20. Has received agents known to directly influence the 5-HT4/acetylcholine prokinetic mechanism (eg, serotonin-specific reuptake inhibitors, anticholinergic agents, or acetylcholinesterase inhibitors) within the 72 hours before Randomisation.
21. Has a history of hypersensitivity or allergies to TAK-954 or metoclopramide.
22. Is female and lactating or pregnant or intending to become pregnant within 30 days after last dose of the study medication; or intending to donate ova during such time period.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to assess the treatment effect of IV TAK-954 in improving the average daily protein adequacy received through enteral nutrition.;Secondary Objective: • Assess the treatment effect of TAK-954 on GRV.<br>• Assess the safety and tolerability of multiple IV doses of TAK-954. <br>• Assess the treatment effect of TAK-954 on the ability to meet average target daily nutritional goals.<br>• Assess the treatment effect of TAK-954 on clinical outcomes.<br>• Evaluate the PK of TAK-954.<br>;Primary end point(s): The primary efficacy endpoint will be the average daily protein adequacy received through enteral nutrition (defined by % of goal protein delivered per day [% protein goal delivered = actual protein achievement / total patient-specific target protein]) over the first 5 days of study treatment.;Timepoint(s) of evaluation of this end point: 5 days.
- Secondary Outcome Measures
Name Time Method