Last updated: 11/07/2018 04:51:56

Evaluation of single doses of GSK962040 in critically ill patients with enteral feed intolerance

Request patient level data
GSK study ID
112571
See study documents
Clinicaltrials.gov ID
NCT01039805
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A double-blind, randomized, placebo controlled Phase II study to evaluate the pharmacodynamics, safety, tolerability, and pharmacokinetics of Single Doses of the Oral Motilin Receptor Agonist GSK962040, in critically ill male and female patients with enteral feed intolerance
Trial description: The aims of MOT112571 are to assess the pharmacodynamic effects, safety, tolerability, pharmacokinetics, and potential therapeutic benefit of single doses of GSK962040 in critically ill patients with delayed gastric emptying and who are intolerant to enteral feeding.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:

Summary of gastric half emptying time (T1/2b) and duration of the lag time (T-lag) measured by the 13C octanoic acid breath test as a measure of gastric emptying (GE)

Timeframe: Baseline (Day -1) and Day 1

Summary of gastric evacuation coefficient (GEC) measured by the 13C octanoic acid breath test as a measure of GE

Timeframe: Baseline (Day -1) and Day 1

Number of participants with adverse events (AEs) and serious adverse events (SAE)

Timeframe: AE and SAE were collected from Day -1 till follow-up (7-10 days post dose, approximately 16 days)

Change from Baseline (Day 1 pre-dose) in systolic blood pressure (SBP) and diastolic blood pressure (DBP)

Timeframe: Baseline (Day 1 pre-dose) and up to Day 5

Change from Baseline (Day 1 pre-dose) in heart rate

Timeframe: Baseline (Day 1 pre-dose) and up to Day 5

Change from Baseline (Day 1 pre-dose) in electrocardiography (ECG) parameters

Timeframe: Baseline (Day 1 pre-dose) and up to 12 hours on Day 1

Change from Baseline (Day -1) in urea/blood urea nitrogen (BUN), glucose, sodium, potassium, calcium and chloride

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in creatinine, uric acid, direct bilirubin and total bilirubin

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in total protein and albumin

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT)

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cells (WBC)

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in hemoglobin and mean corpuscular hemoglobin concentration (MCHC)

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in hematocrit

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in mean corpuscle volume (MCV)

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in mean corpuscle hemoglobin (MCH)

Timeframe: Baseline (Day -1) and up to Day 5

Change from Baseline (Day -1) in red blood cell (RBC) and reticulocytes

Timeframe: Baseline (Day -1) and up to Day 5

Pharmacokinetic parameters of GSK962040: maximum observed concentration (C-max)

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4.5, 5.5, 7.5, 13.5, 25.5 and 37.5 hours

Time of occurrence of Cmax (T-max) and terminal phase half-life (T-half) of GSK962040

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4.5, 5.5, 7.5, 13.5, 25.5 and 37.5 hours

Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) and area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC[0-t]) of GSK962040

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4.5, 5.5, 7.5, 13.5, 25.5 and 37.5 hours

Apparent clearance following oral dosing (CL/F) of GSK962040

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4.5, 5.5, 7.5, 13.5, 25.5 and 37.5 hours

Apparent volume of distribution (V/F) after extravascular (for example oral) administration

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4.5, 5.5, 7.5, 13.5, 25.5 and 37.5 hours

Secondary outcomes:

Pre and post GSK962040 dose gastric residual volume (GRV)

Timeframe: Pre-testing and 10 hours on Day -1 and Pre-dose, 10, 16 and 22 hours on dosing day (Day 1)

Amount of calories delivered over 24 hours

Timeframe: 24 hours post dose (Day 1)

Pharmacokinetic parameters of paracetamol: concentration at 60 minutes

Timeframe: Pre-testing, 0.25, 0.5, 0.75, 1, 1.5, 2 and 4 hours on Day -1, Pre-dose, -1, -0.5, 0.25, 0.5, 0.75, 1, 2 and 4 hours on Day 1

Pharmacokinetic parameters of paracetamol: T-max

Timeframe: Pre-testing, 0.25, 0.5, 0.75, 1, 1.5, 2 and 4 hours on Day -1, Pre-dose, -1, -0.5, 0.25, 0.5, 0.75, 1, 2 and 4 hours on Day 1

Pharmacokinetic parameters of paracetamol: AUC 0-60, AUC 0-120, AUC0-180 and AUC0-360

Timeframe: Pre-testing, 0.25, 0.5, 0.75, 1, 1.5, 2 and 4 hours on Day -1, Pre-dose, -1, -0.5, 0.25, 0.5, 0.75, 1, 2 and 4 hours on Day 1

Pharmacokinetic parameters of 3-OMG: C-max

Timeframe: Pre-testing, 0.25, 0.5, 0.75, 1, 1.5, 2, 3 and 4 hours on Day -1, Pre-dose, -1, -0.5, 0.25, 0.5, 0.75, 1, 2, 3 and 4 hours on Day 1

Pharmacokinetic parameters of 3-OMG: T-max

Timeframe: Pre-testing, 0.25, 0.5, 0.75, 1, 1.5, 2, 3 and 4 hours on Day -1, Pre-dose, -1, -0.5, 0.25, 0.5, 0.75, 1, 2, 3 and 4 hours on Day 1

Pharmacokinetic parameters of 3-OMG: AUC 0-60 and AUC 0-240

Timeframe: Pre-testing, 0.25, 0.5, 0.75, 1, 1.5, 2 and 4 hours on Day -1, Pre-dose, -1, -0.5, 0.25, 0.5, 0.75, 1, 2 and 4 hours on Day 1

Plasma concentrations of motilin when GRV>200 mL and after a single dose of GSK962040

Timeframe: Pre-testing, 1 and 2 hours on Day -1, Pre-dose, 0, 1 and 2 hours on Day 1

Interventions:
  • Drug: GSK962040 (50 mg)
  • Drug: Placebo
  • Drug: GSK962040 (75 mg)
    • Enrollment:
    33
    Primary completion date:
    2011-07-07
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    MJ Chapman, AM Deane, SL O’Connor, NQ Nguyen, RJL Fraser, DB Richards, KE Hacquoil, LS Vasist Johnson, ME Barton, GE Dukes. The effect of Camicinal (GSK962040), a motilin agonist, on gastric emptying and glucose absorption in feed-intolerant critically ill patients: a randomized, blinded, placebo-controlled, clinical trial. Crit Care. 2016;20(1):232.
    Medical condition
    Gastroparesis
    Product
    camicinal
    Collaborators
    Not applicable
    Study date(s)
    December 2009 to July 2011
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 85 years
    Accepts healthy volunteers
    No
    • Male or female between 18-85 years of age, at the time consent is obtained.
    • Mechanically ventilated on the Intensive Care Unit who has become intolerant of nasogastric enteral feeding.
    • Subjects that have received a gastric prokinetic agent in the previous 24 h (e.g., erythromycin, azithromycin, metoclopramide). These agents are prohibited for the duration of the study.
    • Subjects whose clinical condition is deteriorating rapidly or any subject for whom the investigator does not consider there is a reasonable expectation that they will be able to complete the study.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Male or female between 18-85 years of age, at the time consent is obtained.
    • Mechanically ventilated on the Intensive Care Unit who has become intolerant of nasogastric enteral feeding.
    • intolerance of nasogastric tube feeding is defined as a gastric aspirate volume (GRV) >250 mL at least 6 hours after commencing feeding at >40 mL/hr.
    • Expected to remain mechanically ventilated for at least 48 hours after enrollment and expected to survive for at least 24 hours post dose of study medication.
    • Subject has a nasogastric tube for enteral feeding.
    • Body weight > or = 50 kg
    • Written informed consent may be obtained from a legally acceptable representative, which includes compliance with the requirements and restrictions listed in the consent form. In most cases, consent will be sought from next of kin as the subject will not be competent to give their own consent.
    • Average QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
    • AST and ALT < 3xULN; alkaline phosphatase and bilirubin < or = 2xULN.
    • Subjects who have rapidly rising aminotransferases or for whem there is not a plausible explanation for the observed elevation will not be enrolled
    • LFTs will be checked for eligibility on screening and again prior to dosing with GSK962040.
    Exclusion criteria:
    • Subjects that have received a gastric prokinetic agent in the previous 24 h (e.g., erythromycin, azithromycin, metoclopramide). These agents are prohibited for the duration of the study.
    • Subjects whose clinical condition is deteriorating rapidly or any subject for whom the investigator does not consider there is a reasonable expectation that they will be able to complete the study.
    • Subjects who are known to be infected with Hepatitis B, Hepatitis C, or HIV viruses.
    • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
    • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
    • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
    • Use of prohibited medications listed in Section 9.2 within the restricted timeframe relative to dosing of study medication.
    • Subjects with renal failure requiring replacement therapy (dialysis or filtration).
    • Subjects for whom the reason for admission to ICU was an overdose (deliberate or accidental; medicinal product or not).
    • Subjects with altered upper gastrointestinal tract anatomy and subjects who have undergone upper gastrointestinal tract surgery on this admission to ICU.
    • Subjects with bowel obstruction or perforation.
    • Subject has a gastric pacemaker
    • Subject is receiving parenteral feeding
    • 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.
    • Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
    • Lactating females.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Adelaide, South Australia, Australia, 5000
    Status
    Study Complete
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2011-07-07
    Actual study completion date
    2011-07-07

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Participate in clinical trial
    Additional information
    Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
    Click here
    Access to clinical trial data by researchers
    Visit website