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

Phase 1

Completed

• Conditions: Enteral Feeding Intolerance
• Interventions: Drug: Metoclopramide; Drug: TD-8954

• Registration Number: NCT01953081
• Lead Sponsor: Takeda

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-09-25
• Study First Submitted QC: 2013-09-25
• Study First Posted: 2013-09-30
• Study Start: 2014-01
• Primary Completion: 2014-09
• Study Completion: 2014-10
• Results First Submitted: 2016-12-20
• Results First Submitted QC: 2017-05-16
• Results First Posted: 2017-06-14
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-05
• Last Update Posted: 2020-02-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metoclopramide	Metoclopramide	Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
TD-8954	TD-8954	TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours

Primary Outcome Measures

Name	Time	Method
Adverse Events	6 Days	the number of subjects reporting adverse events by treatment group
Gastric Retention by Scintigraphy	180 minutes	Number of subjects with retention less than 13% at 180 minutes after dosing.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia