A Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of a Single Dose of Intravenous TD-8954 Compared With Metoclopramide in Critically Ill Patients With Enteral Feeding Intolerance

Study Overview
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Brief Summary
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This study is being conducted to evaluate the safety, tolerability and early efficacy of IV TD 8954 compared to metoclopramide in critically ill subjects, aged 18 to 85 years, who are admitted to the intensive care require mechanical ventilation, and are intolerant to enteral feeding.

Official Title
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A Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of a Single Dose of Intravenous TD-8954 Compared With Metoclopramide in Critically Ill Patients With Enteral Feeding Intolerance

Conditions
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Enteral Feeding Intolerance

Intervention / Treatment
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* Drug: TD-8954
* Drug: Metoclopramide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Intubated, on mechanical ventilation, and anticipated to remain on mechanical ventilation for 2 days after enrollment into the study Receiving enteral feeding and assessed to have developed EFI, as defined by a GRV measurement ≥250 mL within the 24 hours before randomization Exclusion Criteria: History of diabetic or idiopathic gastroparesis Screening blood glucose >15 mmol/L (270 mg/dL) while receiving insulin Impaired renal function, as defined by estimated glomerular filtration rate (eGFR) <30 mL/min, as determined by the Cockcroft-Gault formula -Bilirubin concentration in blood >2 times the upper limit of normal ALT or AST >3 times upper limit of normal Alkaline phosphatase >2 times upper limit of normal Contraindication to enteral feeding Opioid or other drug overdose as the primary reason for admission to Intensive Care Unit (ICU) Receipt of a drug that can be used as a gastric prokinetic agent Receipt of agents known to directly influence the 5 HT4/acetylcholine prokinetic mechanism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: TD-8954<br>TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours | Drug: TD-8954<br> <br> |
| Active Comparator: Metoclopramide<br>Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline | Drug: Metoclopramide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | the number of subjects reporting adverse events by treatment group | 6 Days | 
| Gastric Retention by Scintigraphy | Number of subjects with retention less than 13% at 180 minutes after dosing. | 180 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time to maximal concentration in plasma | 72 hours | 
| AUC | Area under the plasma concentration time curve from 0 to 72 hours after dosing. | 72 hours | 
| Cmax | Maximum plasma concentration | 72 hours | 
| Gastric Emptying by Breath Test | Time to 1/2 gastric emptying by breath test | 180 minutes | 
| Percentage Gastric Retention by Scintigraphy at 60 Minutes Postdose | Mean gastric retention percentage after dosing. | 60 minutes | 
| Percentage Gastric Retention by Scintigraphy at 120 Minutes Postdose | Mean gastric retention percentage after dosing. | 120 minutes | 
| Percentage of Gastric Retention by Scintigraphy at 240 Minutes Postdose | Mean gastric retention percentage after dosing. | 240 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enteral feeding