Nutritional Adequacy Therapeutic Enhancement in the Critically Ill. The NUTRIATE Study

NCT01934192 | Terminated Phase 2 Results DMC

• 1 other identifier: 113445
• Study Type: interventional
• Target: 91
• Locations: 3 countries
• Sites: 19

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.

Conditions

Gastroparesis

Keywords

tolerability; camicinal; single dose; acetaminophen; gastric emptying; critically ill; GSK962040; pharmacokinetics; pharmacodynamics; gut motility

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to Day 7

• 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.

  Up to Day 7

Secondary Outcomes (35)

• Average Percentage Goal Calories Delivered Prior to Development of Intolerance

  Up to Day 7

• Average Percentage Goal Protein Delivered Prior to Development of Intolerance

  Up to Day 7

• Time to Delivery of 80 Percent Prescribed Calories Prior to Intolerance

  Up to Day 7

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  up to 23 days

• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Up to 23 days

Study Arms (4)

Initial randomization: GSK962040 Arm

EXPERIMENTAL

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

Drug: GSK962040 50 mg

Initial randomization: Placebo Arm

PLACEBO COMPARATOR

Subjects in the placebo arm will receive once daily dose enteral dose administered through NG tube up to 7 days.

Drug: Placebo NG

Treatment change due to intolerance: GSK962040 Arm

EXPERIMENTAL

Subjects that develop intolerance and that originally received Placebo will receive 50 mg once daily enteral dose administered through NG tube + placebo IV

Drug: GSK962040 50 mg; Drug: Placebo IV

Treatment change due to intolerance: Metoclopramide Arm

ACTIVE COMPARATOR

Subjects that develop intolerance and that originally received GSK962040 will receive metoclopramide 10 mg IV every 6 h + placebo NG

Drug: Metoclopramide 10 mg; Drug: Placebo NG

Interventions

GSK962040 50 mg DRUG

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

Initial randomization: GSK962040 Arm; Treatment change due to intolerance: GSK962040 Arm

Metoclopramide 10 mg DRUG

Metoclopramide will be administered IV every 6 h

Treatment change due to intolerance: Metoclopramide Arm

Placebo NG DRUG

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

Initial randomization: Placebo Arm; Treatment change due to intolerance: Metoclopramide Arm

Placebo IV DRUG

Placebo will be administered IV every 6 hours

Treatment change due to intolerance: GSK962040 Arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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 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).
• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (19)

GSK Investigational Site

Aurora, Colorado, 80045, United States

Location

GSK Investigational Site

Augusta, Georgia, 30909, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40202, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Southport, Queensland, 4215, Australia

Location

GSK Investigational Site

Adelaide, South Australia, 5000, Australia

Location

GSK Investigational Site

Woodville, South Australia, 5011, Australia

Location

GSK Investigational Site

Calgary, Alberta, T1Y 6J4, Canada

Location

GSK Investigational Site

Calgary, Alberta, T2N 2T9, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8L 2X2, Canada

Location

GSK Investigational Site

Kingston, Ontario, K7L 2V7, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1Y 4E9, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 1X5, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 3J4, Canada

Location

GSK Investigational Site

Québec, Quebec, G1J 1Z4, Canada

Location

GSK Investigational Site

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

MeSH Terms

Conditions

Gastroparesis; Critical Illness

Interventions

N-(3-fluorophenyl)-1-((4-(((3S)-3-methyl-1-piperazinyl)methyl)phenyl)acetyl)-4-piperidinamine; Metoclopramide

Condition Hierarchy (Ancestors)

Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2013
• First Posted: September 4, 2013
• Study Start: April 4, 2014
• Primary Completion: July 8, 2016
• Study Completion: July 8, 2016
• Last Updated: December 11, 2017
• Results First Posted: November 9, 2017

Record last verified: 2017-10

Locations

AU (4); CA (11); US (4)