Enteral Feeding Intolerance
Conditions
Keywords
Enteral feeding
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.
Interventions
DRUGTD-8954
DRUGMetoclopramide
Sponsors
Theravance Biopharma
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 72 hours | Maximum plasma concentration |
| Gastric Emptying by Breath Test | 180 minutes | Time to 1/2 gastric emptying by breath test |
| Tmax | 72 hours | Time to maximal concentration in plasma |
| 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. |
| Percentage Gastric Retention by Scintigraphy at 60 Minutes Postdose | 60 minutes | Mean gastric retention percentage after dosing. |
| AUC | 72 hours | Area under the plasma concentration time curve from 0 to 72 hours after dosing. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TD-8954 TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours | 7 |
| Metoclopramide Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | TD-8954 | Metoclopramide | Total |
|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 25.29 | 55.5 years STANDARD_DEVIATION 13.37 | 54.7 years STANDARD_DEVIATION 19.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 13 Participants |
| Region of Enrollment Australia | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 2 / 6 |
| serious Total, serious adverse events | 2 / 7 | 3 / 6 |
Outcome results
Primary
Adverse Events
the number of subjects reporting adverse events by treatment group
Time frame: 6 Days
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TD-8954 | Adverse Events | 5 participants |
| Metoclopramide | Adverse Events | 4 participants |
Primary
Gastric Retention by Scintigraphy
Number of subjects with retention less than 13% at 180 minutes after dosing.
Time frame: 180 minutes
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TD-8954 | Gastric Retention by Scintigraphy | 6 participants |
| Metoclopramide | Gastric Retention by Scintigraphy | 3 participants |
Secondary
AUC
Area under the plasma concentration time curve from 0 to 72 hours after dosing.
Time frame: 72 hours
Population: One subject did not receive the full dose of TD-8954 and was excluded from PK analysis for the TD-8954 group; Metoclopramide concentrations were not measured in the Metoclopramide group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TD-8954 | AUC | 23200 pg*hr/mL | Standard Deviation 9240 |
Secondary
Cmax
Maximum plasma concentration
Time frame: 72 hours
Population: One subject did not receive the full dose of TD-8954 and was excluded from PK analysis for the TD-8954 group; Metoclopramide concentrations were not measured in the Metoclopramide group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TD-8954 | Cmax | 5040 pg/mL | Standard Deviation 1780 |
Secondary
Gastric Emptying by Breath Test
Time to 1/2 gastric emptying by breath test
Time frame: 180 minutes
Population: One subject in the TD-8954 group did not receive the full dose of TD-8954 and was excluded from the TD-8954 analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TD-8954 | Gastric Emptying by Breath Test | 135.7 minutes | Standard Deviation 41.61 |
| Metoclopramide | Gastric Emptying by Breath Test | 132.5 minutes | Standard Deviation 53.87 |
Secondary
Percentage Gastric Retention by Scintigraphy at 120 Minutes Postdose
Mean gastric retention percentage after dosing.
Time frame: 120 minutes
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TD-8954 | Percentage Gastric Retention by Scintigraphy at 120 Minutes Postdose | 19.6 percentage of retention | Standard Deviation 36.1 |
| Metoclopramide | Percentage Gastric Retention by Scintigraphy at 120 Minutes Postdose | 32.3 percentage of retention | Standard Deviation 28.32 |
Secondary
Percentage Gastric Retention by Scintigraphy at 60 Minutes Postdose
Mean gastric retention percentage after dosing.
Time frame: 60 minutes
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TD-8954 | Percentage Gastric Retention by Scintigraphy at 60 Minutes Postdose | 29.6 percentage of retention | Standard Deviation 36.28 |
| Metoclopramide | Percentage Gastric Retention by Scintigraphy at 60 Minutes Postdose | 43.3 percentage of retention | Standard Deviation 30.14 |
Secondary
Percentage of Gastric Retention by Scintigraphy at 240 Minutes Postdose
Mean gastric retention percentage after dosing.
Time frame: 240 minutes
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TD-8954 | Percentage of Gastric Retention by Scintigraphy at 240 Minutes Postdose | 11.1 percentage of retention | Standard Deviation 24.85 |
| Metoclopramide | Percentage of Gastric Retention by Scintigraphy at 240 Minutes Postdose | 16.3 percentage of retention | Standard Deviation 25.64 |
Secondary
Tmax
Time to maximal concentration in plasma
Time frame: 72 hours
Population: PK Analysis set for subjects receiving TD-8954, metoclopramide concentrations were not measured in the metoclopramide group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TD-8954 | Tmax | 0.500 hours |