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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01934192




Registration number
NCT01934192
Ethics application status
Date submitted
29/08/2013
Date registered
4/09/2013
Date last updated
11/12/2017

Titles & IDs
Public title
Nutritional Adequacy Therapeutic Enhancement in the Critically Ill. The NUTRIATE Study
Scientific title
NUTRItional Adequacy Therapeutic Enhancement in the Critically Ill: A Randomized Double Blind, Placebo-controlled Trial of the Motilin Receptor Agonist GSK962040. The NUTRIATE Study
Secondary ID [1] 0 0
113445
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastroparesis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK962040 50 mg
Treatment: Drugs - Metoclopramide 10 mg
Treatment: Drugs - Placebo NG
Treatment: Drugs - Placebo IV

Experimental: Initial randomization: GSK962040 Arm - Subjects in the GSK962040 Arm will receive 50 mg once daily enteral dose administered through NG tube up to 7 days.

Placebo Comparator: Initial randomization: Placebo Arm - Subjects in the placebo arm will receive once daily dose enteral dose administered through NG tube up to 7 days.

Experimental: Treatment change due to intolerance: GSK962040 Arm - Subjects that develop intolerance and that originally received Placebo will receive 50 mg once daily enteral dose administered through NG tube + placebo IV

Active Comparator: Treatment change due to intolerance: Metoclopramide Arm - Subjects that develop intolerance and that originally received GSK962040 will receive metoclopramide 10 mg IV every 6 h + placebo NG


Treatment: Drugs: GSK962040 50 mg
GSK962040 50 mg will be administered once daily enteral dose through NG tube up to 7 days.

Treatment: Drugs: Metoclopramide 10 mg
Metoclopramide will be administered IV every 6 h

Treatment: Drugs: Placebo NG
Matching placebo once daily enteral dose will be administered through NG tube up to 7 days

Treatment: Drugs: Placebo IV
Placebo will be administered IV every 6 hours

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Average Percentage Goal Volume Delivered Prior to Development of Intolerance for ITT Population - The average percentage goal volume received via EN was defined as the percent of goal volume received via EN from the first study dose up to permanent discontinuation of EN. It is calculated as 100 multiplied by total volume received via EN during the on treatment period prior to intolerance divided by total prescribed volume. 'Prior to intolerance' means 'prior to start of intolerance treatment. One participant was missing for prior to start of intolerance treatment. The average percentage goal volume received via EN was assessed and comparison between Camicinal 50mg and placebo arm was performed. Adjusted mean and its 95% confidence interval (CI) were estimated and Analysis of Covariance (ANCOVA) model was used for analysis.
Timepoint [1] 0 0
Up to Day 7
Primary outcome [2] 0 0
Average Percentage Goal Volume Delivered Prior to Development of Intolerance for PP Population - The average percentage goal volume received via EN was defined as the percent of goal volume received via EN from the first study dose up to permanent discontinuation of EN. It is calculated as 100 multiplied by total volume received via EN during the on treatment period prior to intolerance divided by total prescribed volume. 'Prior to intolerance' means 'prior to start of intolerance treatment. One participant was missing for prior to start of intolerance treatment. The average percentage goal volume received via EN was assessed and comparison between Camicinal 50mg and placebo arm was performed. Adjusted mean and its 95% CI were estimated and ANCOVA model was used for analysis.
Timepoint [2] 0 0
Up to Day 7
Secondary outcome [1] 0 0
Average Percentage Goal Calories Delivered Prior to Development of Intolerance - The average percentage goal calories received via EN was defined as the percent of goal calories received via EN from the first study dose up to permanent discontinuation of EN. It is calculated as 100 multiplied by total calories received via EN during the on treatment period prior to intolerance divided by total prescribed calories. 'Prior to intolerance' means 'prior to start of intolerance treatment. The average percentage goal calories received via EN was assessed and comparison between Camicinal 50mg and placebo arm was performed. Adjusted mean and its 95% CI were estimated and ANCOVA model was used for analysis.
Timepoint [1] 0 0
Up to Day 7
Secondary outcome [2] 0 0
Average Percentage Goal Protein Delivered Prior to Development of Intolerance - The average percentage goal protein received via EN was defined as the percent of goal protein received via EN from the first study dose up to permanent discontinuation of EN. It is calculated as 100 multiplied by total protein received via EN during the on treatment period prior to intolerance divided by total prescribed protein. 'Prior to intolerance' means 'prior to start of intolerance treatment. One participant was missing for prior to start of intolerance treatment. The average percentage goal protein received via EN was assessed and comparison between Camicinal 50mg and placebo arm was performed. Adjusted mean and its 95% CI were estimated and ANCOVA model was used for analysis.
Timepoint [2] 0 0
Up to Day 7
Secondary outcome [3] 0 0
Time to Delivery of 80 Percent Prescribed Calories Prior to Intolerance - Time required for the delivery of 80 percent prescribed calories prior to intolerance was calculated using Kaplan-Meier estimates for time variable. Prior to intolerance was defined as prior to start of intolerance treatment. Participants who did not reach delivery of 80 percent prescribed calories were censored at the last day on which they received randomized treatment and with available nutritional data.
Timepoint [3] 0 0
Up to Day 7
Secondary outcome [4] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE.
Timepoint [4] 0 0
up to 23 days
Secondary outcome [5] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) - SBP and DBP were measured at Baseline, Day 1, up to 6 hrs pre-dose on Day 2-7 and at follow-up (till 23 days). The Baseline value was considered to be the participant's last available assessment prior to randomized treatment. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, SBP and DBP were measured at Day 1 to Day 7 post-intolerance. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the standard deviation (SD) was set to missing.
Timepoint [5] 0 0
Up to 23 days
Secondary outcome [6] 0 0
Change From Baseline in Heart Rate (HR) - HR was measured at Baseline, Day 1, up to 6 hrs pre-dose on Day 2-7 and at follow-up (till Day 23). The Baseline value was considered to be the participant's last available assessment prior to randomized treatment. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, HR was measured at Day 1 to Day 7 post-intolerance. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [6] 0 0
Up to 23 days
Secondary outcome [7] 0 0
Number of Participants With Maximum Increase From Baseline in Electrocardiogram (ECG) Values - 12-lead ECGs was done at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 and at follow up (till Day 23) that automatically calculates corrected QT (QTc), QTcF (QT duration corrected for heart rate by Fridericia's formula) and QTcB (QT duration corrected for heart rate by Bazett's formula) intervals. Three ECGs approximately 5 min apart were collected prior to dose 1and single recordings were made at other time points. On Day 1ECGs were collected at pre-dose (up to 6 hrs) and 2 hr post treatment. Number of participants with maximum increase from Baseline were collected and participants showed increase in 3 parameters namely QTc, QTcB and QTcF. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Timepoint [7] 0 0
Up to 23 days
Secondary outcome [8] 0 0
Change From Baseline in Albumin and Total Protein Levels - Blood samples were collected to evaluate change from Baseline in albumin and total protein values at Baseline, Day 2-7 and follow-up (till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [8] 0 0
Up to 23 days
Secondary outcome [9] 0 0
Change From Baseline in Alkaline Phosphatase (Alk. Phosph.), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Levels - Blood samples were collected to evaluate change from Baseline in alk.phosp., ALT, AST and GGT values at Baseline, Day 1- Day 7 and follow up (till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles). If n < 3 the SD was set to missing.
Timepoint [9] 0 0
Up to 23 days
Secondary outcome [10] 0 0
Change From Baseline in Total and Direct Bilirubin, Creatinine and Uric Acid Levels - Blood samples were collected to evaluate change from Baseline in total and direct bilirubin, creatinine and uric acid values at Baseline, Day 2- Day 7 and at follow up (Till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles). If n < 3 the SD was set to missing.
Timepoint [10] 0 0
Up to 23 days
Secondary outcome [11] 0 0
Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Blood Urea Nitrogen (BUN) Values - Blood samples were collected to evaluate change from Baseline in calcium, chloride, carbon dioxide, glucose, potassium, sodium, BUN values at Baseline, up to Day 7 and follow up (till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [11] 0 0
Up to 23 days
Secondary outcome [12] 0 0
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet and White Blood Cell (WBC) Levels - Blood samples were collected to evaluate change from Baseline in basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet and WBC values at Baseline up to Day 7 and follow up (till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [12] 0 0
Up to 23 days
Secondary outcome [13] 0 0
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Levels - Blood samples were collected to evaluate change from Baseline in hemoglobin and MCHC values at Baseline up to Day 7 and follow up (till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [13] 0 0
Up to 23 days
Secondary outcome [14] 0 0
Change From Baseline in Hematocrit Level - Blood samples were collected to evaluate change from Baseline in hematocrit values at Baseline up to Day 7 and follow up (till day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [14] 0 0
Up to 23 days
Secondary outcome [15] 0 0
Change From Baseline in Mean Corpuscle Volume (MCV) Levels - Blood samples were collected to evaluate change from Baseline in MCV values at Baseline up to Day 7 and follow up (till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [15] 0 0
Up to 23 days
Secondary outcome [16] 0 0
Change From Baseline in Red Blood Cell (RBC) and Reticulocyte Count - Blood samples were collected to evaluate change from Baseline in RBC and reticulocytes values at Baseline up to Day 7 and follow up (till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [16] 0 0
Up to 23 days
Secondary outcome [17] 0 0
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Levels - Blood samples were collected to evaluate change from Baseline in MCH values at Baseline up to Day 7 and follow up (till Day 23). Blood samples were also collected on Day 9 for those participants who completed 7 days of dosing. Change from Baseline was defined as post dose visit value minus Baseline value. For participants who developed intolerance, blood samples were taken for Day 1 to Day 7 up to 6 hrs prior to dosing. NA indicates that data were not available. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). If n < 3 the SD was set to missing.
Timepoint [17] 0 0
Up to 23 days
Secondary outcome [18] 0 0
Log Transformed Concentration at 60 Minutes (Min) (C60) and Maximum Observed Concentration (Cmax) of Acetaminophen (Prior to Intolerance) - Blood samples for pharmacokinetic (PK) analysis were collected at Baseline, and at Day 2 or at Day 3 (OR very rarely Day 4 - only if Day 2 or Day 3 sample could not be obtained) prior to intolerance. Prior to intolerance was defined as prior to development of intolerance. C60 was defined as observed plasma concentration at 60 min after administration of enteral feed with acetaminophen and Cmax was defined as maximum observed plasma concentration of acetaminophen. The absorption profile of acetaminophen was used as an indirect measure of gastric emptying function. The analysis was performed on ITT (exposed) Population. Due to change in sampling schedule, samples were only obtained to 4 hours. Only those participants available at the specified time points were analyzed (represented by n= x in the category titles).
Timepoint [18] 0 0
At Day 2
Secondary outcome [19] 0 0
Log Transformed AUC[0-60] of Acetaminophen - Blood samples for PK analysis were collected at Baseline, and at 60 min. at Day 2 or Day 3 (or very rarely Day 4 - only if Day 2 or Day 3 sample could not be obtained) prior to intolerance. Prior to intolerance was defined as prior to development of intolerance. AUC[0-60] of acetaminophen was defined as area under the concentration-time curve from time zero to 60 min. and it was calculated as Log trapezoidal rule from concentration-time data. The absorption profile of acetaminophen was used as an indirect measure of gastric emptying function. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles)
Timepoint [19] 0 0
At Day 2
Secondary outcome [20] 0 0
Log Transformed AUC[0-60] of 3-O-methylglucose (3- OMG) - Blood samples for PK analysis were collected at Baseline, and at Day 2 or Day 3 (or very rarely Day 4 - only if Day 2 or Day 3 sample could not be obtained) prior to intolerance. Prior to intolerance was defined as prior to development of intolerance. AUC[0-60] of 3-OMG was defined as area under the concentration-time curve from time zero to 60 min. and it was calculated as Log trapezoidal rule from concentration-time data. The absorption profile of 3-OMG was used as an indirect measure of gastric emptying function. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles)
Timepoint [20] 0 0
At Day 2
Secondary outcome [21] 0 0
Log Transformed C60 of 3-OMG - Blood samples for PK analysis were collected at Baseline and at Day 2 or Day 3 (or very rarely at Day 4 - only if Day 2 or Day 3 sample could not be obtained)prior to intolerance. Prior to intolerance was defined as prior to development of intolerance. C60 was defined as observed plasma concentration at 60 min after administration of enteral feed with 3-OMG. The absorption profile of 3-OMG was used as an indirect measure of gastric emptying function. The analysis was performed on ITT (exposed) Population. Cmax was not analyzed. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Timepoint [21] 0 0
At Day 2
Secondary outcome [22] 0 0
Derived Tmax of 3-OMG Post Intolerance - Blood samples for PK analysis were collected at Day 2 or Day 3 (or very rarely at Day 4 - only if Day 2 or Day 3 sample could not be obtained) post development of intolerance. Tmax was defined as time to maximum observed plasma concentration of 3-OMG.
Timepoint [22] 0 0
At Day 2
Secondary outcome [23] 0 0
Percentage of Participants That Became Intolerant - Percentage of participants that became intolerant was calculated. Those participants who developed intolerance were assessed to characterize gastric emptying (GE). Participants who did not develop intolerance were censored at the time of the last available Gastric Residual Volume (GRV) measurement.
Timepoint [23] 0 0
Up to Day 7
Secondary outcome [24] 0 0
Time to Development of Feeding Intolerance - Time required for the development of feeding intolerance was calculated using Kaplan-Meier estimates for time variable. Median and quartiles were not calculable due to the small number of participants developing EN intolerance and mean and standard error of mean were presented.
Timepoint [24] 0 0
Up to Day 7
Secondary outcome [25] 0 0
GE Assessment as AUC (0-60) Within 24 Hrs of Developing Intolerance and Prior to Change of Treatment Using Acetaminophen - GE assessment within 24 hrs of developing intolerance and prior to change of treatment was analyzed using acetaminophen absorption method. AUC (0-60) was calculated and data was presented for pre-dose Visit (day prior to change of treatment). Geometric mean and 95 percent CI was analyzed.
Timepoint [25] 0 0
Day 2
Secondary outcome [26] 0 0
GE Assessment as Cmax Within 24 Hrs of Developing Intolerance and Prior to Change of Treatment Using Acetaminophen - GE assessment within 24 hrs of developing intolerance and prior to change of treatment was analyzed using acetaminophen absorption method. Cmax was calculated and data was presented for pre-dose Visit(day prior to change of treatment). Geometric mean and 95 percent CI was analyzed.
Timepoint [26] 0 0
Baseline, Day 2, Day 3, Day 4
Secondary outcome [27] 0 0
GE Assessment as AUC (0-60) and AUC (0-240) Within 24 Hrs of Developing Intolerance and Prior to Change of Treatment Using 3-OMG - GE assessment within 24 hrs of developing intolerance and prior to change of treatment was analyzed using 3-OMG absorption method. AUC(0-60) and AUC (0-240) was calculated and data was presented for pre-dose Visit (day prior to change of treatment). Geometric mean and 95 percent CI was analyzed.
Timepoint [27] 0 0
Baseline, Day 2, Day 3, Day 4
Secondary outcome [28] 0 0
GE Assessment as C60 Within 24 Hrs of Developing Intolerance and Prior to Change of Treatment Using 3-OMG - GE assessment within 24 hrs of developing intolerance and prior to change of treatment was analyzed using 3-OMG absorption method. C60 was calculated and data was presented for pre-dose Visit (day prior to change of treatment). Geometric mean and 95 percent CI was analyzed.
Timepoint [28] 0 0
Baseline, Day 2, Day 3, Day 4
Secondary outcome [29] 0 0
Number of Participants With Occurrences of Vomiting, Regurgitation and Macroaspiration Episodes - The total number of vomiting, regurgitation and macroaspiration episodes were categorized separately for prior to and post intolerance. Intolerance was considered as start of intolerance treatment. Only the records with non-zero counts were listed.
Timepoint [29] 0 0
up to 23 days
Secondary outcome [30] 0 0
Total GRV for 24 hr Period - Total GRV for each 24 hr period up to 7 days were assessed to determine the effect of GSK962040 vs. Placebo upon the daily GRV. Intolerance was defined as start of the intolerance treatment. The total GRV for each 24hr period was the sum of all available GRV measurements during the period. The 24hr was counted using the same 24hr clock as for the collection of nutritional data.
Timepoint [30] 0 0
Up to Day 7
Secondary outcome [31] 0 0
Log Transformed Derived Plasma Cmax of GSK962040 Prior to Intolerance - Blood samples for PK analysis were collected at Day 2, Day 3, Day 4, Day 7 prior to intolerance. Prior to intolerance was defined as prior to development of intolerance. Cmax was defined as maximum observed plasma concentration of Camicinal. The analysis was performed on PK Population. PK Population comprised of participants in the 'Safety' population for whom a PK sample of Camicinal was obtained and analyzed. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Timepoint [31] 0 0
Day 2, Day 3, Day 4, Day 7
Secondary outcome [32] 0 0
Log Transformed Derived Plasma Cmax of GSK962040 Post Intolerance - Blood samples for PK analysis were collected at Day 2 and Day 4 post development of intolerance. Cmax was defined as maximum observed plasma concentration of Camicinal. The analysis was performed on PK Population. NA indicates that data were not available. SD was not provided if n < 3.
Timepoint [32] 0 0
Day 2 and Day 4
Secondary outcome [33] 0 0
Derived Tmax of GSK962040 Post Intolerance - Blood samples for PK analysis were collected at Day 2 and Day 4 post development of intolerance. Tmax was defined as time to maximum observed plasma concentration of Camicinal.NA indicates that data were not available. SD was not provided if n<3.
Timepoint [33] 0 0
Day 2 and Day 4
Secondary outcome [34] 0 0
Derived AUC Over the Dosing Period [AUC(0-tau)] of GSK962040 Post Intolerance - Blood samples for PK analysis were collected at Baseline, and at Day 2 and Day 4 post development of intolerance. AUC from time zero extrapolated to infinite time [AUC(0-inf)] was not analyzed.
Timepoint [34] 0 0
Day 2 and Day 4
Secondary outcome [35] 0 0
Derived Accumulation Ratio (RO) of GSK962040 Post Intolerance - To estimate the extent of accumulation after repeat dosing, the observed accumulation ratio (Ro) was assessed.
Timepoint [35] 0 0
Baseline, Day 2, Day 3, Day 4

Eligibility
Key inclusion criteria
- Age & Gender: Male or female between 18 and 85 years of age inclusive, at the time of
obtaining the informed consent.

- First admitted to participating ICU within the previous 48 hours.

- Intubated and invasively mechanically ventilated

- Indicated to receive early EN or are already receiving EN (subject must be on EN prior
to receiving study treatment)

- Have at least one of the following

- Clinical evidence of cardiovascular dysfunction defined as the need for vasopressor
agents (e.g. norepinephrine, epinephrine, vasopressin), >5 microgram/kg/min of
dopamine, or >/= 50 microgram/min phenylephrine) for greater than or equal to 2 hours;

- Poly-trauma with an injury severity score (ISS) >=15 points

- Acute traumatic or non-traumatic brain injury Glasgow Coma Scale (GCS) <=12, prior to
the initiation of sedation.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects who are not expected to be in the ICU and alive for at least 48 hrs from
point of screening.

- Subjects with acute hepatitis (e.g. acute hepatitis B or C) or severe chronic liver
disease (e.g. Child Pugh class C cirrhosis) will be excluded

- Liver function tests: If Alanine aminotransferase (ALT) >=8x upper limit of normal
(ULN); OR If ALT >5-8x ULN and bilirubin >2<=3 ULN or bilirubin >3x ULN (Include only
if bilirubin <1.5xULN); OR If ALT <=5xULN and Bilirubin >3xULN (Include only if ALT
<=3xULN and Bilirubin >2 <=3xULN)

- Subjects who have received a gastric prokinetic agent in the previous 12 hours (e.g.,
erythromycin, azithromycin, metoclopramide, domperidone).

- QT duration corrected for heart rate (QTc) >480 ms. QTcF is the recommended correction
factor for all sites. If QT duration corrected for heart rate by Fridericia's formula
(QTcF) is not possible to obtain or calculate, QT duration corrected for heart rate by
Bazett's formula (QTcB) or machine or manual over read, may be obtained after
consultation with the medical monitor. The QT correction formula used to determine
inclusion and discontinuation should be the same throughout the study.

- Use of strong Cyp3A4 inhibitors

- Subjects who require renal replacement therapy or with an estimated glomerular
filtration rate (GFR) of <30 mL/min byCockroft-Gault calculation).

- Subjects who have a history of or who have undergone major esophageal or gastric
surgery on this admission (major lower abdominal surgery will not result in exclusion
unless this carries a contraindication to enteral feeding).

- Subjects with an absolute contraindication to enteral nutrition e.g. subjects with
ongoing bowel obstruction or perforation.

- Subject has a gastric pacemaker

- Pregnant or lactating females

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation.

- Concurrent enrollment in other interventional study involving a novel (i.e.unapproved
or experimental) chemical or biopharmaceutical entity.

- Previous randomization in this study

- Subjects for whom the reason for admission to ICU was an overdose (deliberate or
accidental; medicinal product or not).

- Exclusion to re-randomization:

- Subjects with an untreated pheochromocytoma.

- Subjects with a past history of a seizure disorder (e.g., epilepsy) and is currently
receiving anti-epileptic treatment for their seizure disorder, ongoing refractory, or
sustained seizure disorder (prophylactic use for head injury/isolated new seizure
maintained on anti-seizure meds in ICU acceptable).

- Subjects taking drugs likely to cause extrapyramidal reactions.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [2] 0 0
GSK Investigational Site - Southport
Recruitment hospital [3] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [4] 0 0
GSK Investigational Site - Woodville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
Canada
State/province [5] 0 0
Alberta
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, parallel group, placebo-controlled and active-compared, randomized
study to assess the ability of GSK962040 to enhance the delivery of enteral feed to
critically ill subjects that are predisposed to developing feeding intolerance (e.g.,
percentage of goal volume); enhance gastric emptying in this population; and provide
preliminary evidence of the drug's effect on outcomes of therapy (length of stay in the
Intensive Care Unit [ICU], time on ventilator, ICU acquired infections, and 60-day
mortality). Other aims are evaluation of GSK962040 safety, tolerability and pharmacokinetics
upon repeat dosing in a critically ill population.

After meeting eligibility criteria, male and female subjects will be randomized to either
receive GSK962040 (50 milligram [mg]) once daily (OD) via naso-gastric (NG) or orogastric
(OG) feeding tube (oral solution), or placebo by the same route. If subjects develop
intolerance to enteral feeding at any point up to Dose 5 of study medication (inclusive),
study treatments will switch such that those originally receiving GSK962040 will receive
metoclopramide (10 mg, intravenous [iv], every 6 hours) and those subjects originally
randomized to receive placebo will receive GSK962040 (50 mg, via NG, OD). Additionally, if
subjects develop intolerance prior to any treatment, they will be randomized to receive
either GSK962040 (50 mg, via NG, OD) or metoclopramide (10 mg, iv, every 6 hours).

The study will consist of a screening/baseline assessment, a treatment period (up to 7 days
in duration), and a 4-day post treatment safety follow-up assessment. The duration of each
subject's participation in the study from screening to follow-up safety assessment will be up
to approximately 2 weeks. In addition, mortality will be assessed 60 days after admission to
the ICU.
Trial website
https://clinicaltrials.gov/show/NCT01934192
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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GSK Clinical Trials
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GlaxoSmithKline
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Contact person for public queries
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Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01934192