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
Primary Purpose
Enteral Feeding Intolerance
Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
TD-8954
Metoclopramide
Sponsored by
About this trial
This is an interventional treatment trial for Enteral Feeding Intolerance focused on measuring Enteral feeding
Eligibility Criteria
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
Sites / Locations
- Royal Adelaide Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
TD-8954
Metoclopramide
Arm Description
TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours
Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Outcomes
Primary Outcome Measures
Adverse Events
the number of subjects reporting adverse events by treatment group
Gastric Retention by Scintigraphy
Number of subjects with retention less than 13% at 180 minutes after dosing.
Secondary Outcome Measures
Tmax
Time to maximal concentration in plasma
AUC
Area under the plasma concentration time curve from 0 to 72 hours after dosing.
Cmax
Maximum plasma concentration
Gastric Emptying by Breath Test
Time to 1/2 gastric emptying by breath test
Percentage Gastric Retention by Scintigraphy at 60 Minutes Postdose
Mean gastric retention percentage after dosing.
Percentage Gastric Retention by Scintigraphy at 120 Minutes Postdose
Mean gastric retention percentage after dosing.
Percentage of Gastric Retention by Scintigraphy at 240 Minutes Postdose
Mean gastric retention percentage after dosing.
Full Information
NCT ID
NCT01953081
First Posted
September 25, 2013
Last Updated
February 5, 2020
Sponsor
Takeda
Collaborators
Theravance Biopharma
1. Study Identification
Unique Protocol Identification Number
NCT01953081
Brief Title
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
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
Collaborators
Theravance Biopharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Enteral Feeding Intolerance
Keywords
Enteral feeding
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TD-8954
Arm Type
Experimental
Arm Description
TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours
Arm Title
Metoclopramide
Arm Type
Active Comparator
Arm Description
Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Intervention Type
Drug
Intervention Name(s)
TD-8954
Intervention Type
Drug
Intervention Name(s)
Metoclopramide
Primary Outcome Measure Information:
Title
Adverse Events
Description
the number of subjects reporting adverse events by treatment group
Time Frame
6 Days
Title
Gastric Retention by Scintigraphy
Description
Number of subjects with retention less than 13% at 180 minutes after dosing.
Time Frame
180 minutes
Secondary Outcome Measure Information:
Title
Tmax
Description
Time to maximal concentration in plasma
Time Frame
72 hours
Title
AUC
Description
Area under the plasma concentration time curve from 0 to 72 hours after dosing.
Time Frame
72 hours
Title
Cmax
Description
Maximum plasma concentration
Time Frame
72 hours
Title
Gastric Emptying by Breath Test
Description
Time to 1/2 gastric emptying by breath test
Time Frame
180 minutes
Title
Percentage Gastric Retention by Scintigraphy at 60 Minutes Postdose
Description
Mean gastric retention percentage after dosing.
Time Frame
60 minutes
Title
Percentage Gastric Retention by Scintigraphy at 120 Minutes Postdose
Description
Mean gastric retention percentage after dosing.
Time Frame
120 minutes
Title
Percentage of Gastric Retention by Scintigraphy at 240 Minutes Postdose
Description
Mean gastric retention percentage after dosing.
Time Frame
240 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Canafax, PharmD, FCCP
Organizational Affiliation
Theravance Biopharma, US, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
Country
Australia
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31990087
Citation
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.
Results Reference
derived
Learn more about this trial
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
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