TAK-954 in Critically Ill Participants With Enteral Feeding Intolerance (EFI)

Study Overview
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Brief Summary
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The purpose of this study is to assess the treatment effect of intravenous TAK-954 in improving the average daily protein adequacy received through enteral nutrition in critically-ill participants developing EFI.

Detailed Description
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The drug being tested in this study is called TAK-954. The study will assess the treatment effect of intravenous TAK-954 in improving average daily protein adequacy received through enteral nutrition in critically ill participants with EFI. The study will enroll approximately 200 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 4 treatment groups -which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): Group A: TAK-954 0.1 mg Group B: TAK-954 0.3 mg Group C: TAK-954 1 mg Group D: Metoclopramide 10 mg This multi-center trial will be conducted in the United States, United Kingdom, Australia and Canada. The overall duration of treatment in this study is maximum of 14 days while in hospital. Participants will be contacted by telephone 30 and 90 days after receiving their last dose of study drug for a follow-up assessment.

Official Title
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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 Intolerance

Conditions
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Critical Illness, Enteral Nutrition, Enteral Feeding Intolerance

Intervention / Treatment
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* Drug: TAK-954
* Drug: Metoclopramide
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has at least a size 12-(french size) Fr nasogastric or orogastric tube with its tip at least 10 centimeter (cm) below the esophagogastric junction confirmed radiologically (the tip of the tube must be in the body or the antrum of the stomach and not in the fundus). Is intubated and mechanically ventilated in the ICU. Is expected to remain alive, mechanically ventilated, and receive continuous enteral feeding for >=48 hours following randomization. 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. Exclusion Criteria: Is under consideration for withdrawal of life-sustaining treatments within the next 72 hours. 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). Has mechanical bowel obstruction, short bowel syndrome, or the presence of an active gastric pacemaker. 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). Has been admitted primarily for treatment of a drug overdose. Has a presence of a post-pyloric tube in place at Randomization that may be used for enteral nutrition. Is receiving parenteral nutrition (PN) at Screening. Is in diabetic ketoacidosis or non-ketotic hyperosmolar coma. Has a different nutrient requirement than allowed in feeding protocol.(outside a range of 1.2 to 2 gram per kilogram per day [g/kg/day] of proteins and up to 1.5 kilocalorie per milliliter [kcal/mL]).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: TAK-954 0.1 mg<br>TAK-954 0.1 milligram (mg), intravenously, administered as 60 minute-infusion, once daily along with 2 milliliter (mL) normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days. | Drug: TAK-954<br>* TAK-954 infusion<br>Drug: Normal Saline<br>* 0.9% sodium chloride for injection<br>|
| Experimental: Group B: TAK-954 0.3 mg<br>TAK-954 0.3 mg, intravenously, administered as 60 minute-infusion, once daily along with 2 mL normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days. | Drug: TAK-954<br>* TAK-954 infusion<br>Drug: Normal Saline<br>* 0.9% sodium chloride for injection<br>|
| Experimental: Group C: TAK-954 1.0 mg<br>TAK-954 1.0 mg, intravenously, administered as 60 minute-infusion, once daily along with 2 mL normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days. | Drug: TAK-954<br>* TAK-954 infusion<br>Drug: Normal Saline<br>* 0.9% sodium chloride for injection<br>|
| Active Comparator: Group D: Metoclopramide 10 mg<br>Metoclopramide 10 mg, injection, intravenously, three times a day along with 100 mL normal saline 60-minute infusion, intravenously, once daily for a minimum of 5 days up to a maximum of 14 days. | Drug: Metoclopramide<br>* Metoclopramide infusion<br>Drug: Normal Saline<br>* 0.9% sodium chloride for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Daily Protein Adequacy Over the First 5 Days of Treatment | Average daily protein adequacy received through enteral nutrition is defined as the percentage of goal protein delivered per day, where percentage of goal protein delivered is calculated as the ratio of actual protein achievement to the total participant-specific target protein prescribed. The value for each of the 5 days was averaged. | Days 1 to 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Daily Protein Adequacy Over the Study Treatment Period | Average daily protein adequacy received through enteral nutrition is defined as percentage of goal protein delivered per day, where percentage of protein goal delivered is calculated as the ratio of actual protein achievement to the total participant-specific target protein prescribed. The value for each of the 14 days was averaged. | Days 1 to 14 | 
| Average Daily Change in 24-hour Gastric Residual Volume (GRV) Over the First 5 Days of Study Treatment | GRV is defined as the volume of fluid remaining in the stomach at a point in time during enteral nutrition feeding. The value for each of the 5 days was averaged. | Days 1 to 5 | 
| Average Daily Caloric Adequacy | Average daily caloric adequacy received through enteral nutrition was defined by percentage of goal calories achieved per day (percentage calorie goal achieved=actual calorie achievement/total participant-specific target calories). The values in the 5-day period and the 14-day period were averaged. | Days 1 to 5 and Days 1 to 14 | 
| Time to Resolution of Enteral Feeding Intolerance (EFI) | Time to resolution of EFI is defined as the time needed to achieve GRV less than or equal to 250 ml in the absence of vomiting/retching. | Days 1 to 14 or until resolution of EFI, whichever occurs first | 
| Percentage of Participants Achieving at Least 80% of Daily Goal Calories |  | Days 1 to 14 or end of treatment | 
| Percentage of Participants Achieving at Least 80% of Daily Goal Protein |  | Days 1 to 14 or end of treatment | 
| Ctrough: Observed Concentration at the End of a Dosing Interval of TAK-954 |  | Day 5 pre-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy