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

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.

Study Overview

• Status: Completed
• Conditions: Enteral Feeding Intolerance
• Intervention / Treatment: Drug: Metoclopramide; Drug: TD-8954

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TD-8954; TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Drug: TD-8954
ACTIVE_COMPARATOR: Metoclopramide; Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline	Drug: Metoclopramide

What is the study measuring?

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
Cmax	Maximum plasma concentration	72 hours
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
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

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Theravance Biopharma
• Investigators: Study Director: Daniel Canafax, PharmD, FCCP, Theravance Biopharma, US, Inc.

Publications and helpful links

General Publications

• Chapman MJ, Jones KL, Almansa C, Barnes CN, Nguyen D, Deane AM. Blinded, Double-Dummy, Parallel-Group, Phase 2a Randomized Clinical Trial to Evaluate the Efficacy and Safety of a Highly Selective 5-Hydroxytryptamine Type 4 Receptor Agonist in Critically Ill Patients With Enteral Feeding Intolerance. JPEN J Parenter Enteral Nutr. 2021 Jan;45(1):115-124. doi: 10.1002/jpen.1732. Epub 2020 Jan 28.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: September 25, 2013
• First Submitted That Met QC Criteria: September 25, 2013
• First Posted (ESTIMATE): September 30, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Enteral feeding
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Metoclopramide
• Other Study ID Numbers: 0082

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO