Evaluation of Single Doses of GSK962040 in Critically Ill Patients With Enteral Feed Intolerance

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

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.

Study Overview

• Status: Completed
• Conditions: Gastroparesis
• Intervention / Treatment: Drug: Placebo; Drug: GSK962040 (50 mg); Drug: GSK962040 (75 mg)

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Subjects randomized to either GSK962040 (50 mg) or placebo	Drug: Placebo; matching placebo; Drug: GSK962040 (50 mg); Cohort 1 = 50 mg
Experimental: Cohort 2; Subjects randomized to either GSK962040 (75 mg) or placebo	Drug: Placebo; matching placebo; Drug: GSK962040 (75 mg); Cohort 2 = 75 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Gastric emptying	3 days
Safety and tolerability of GSK962040	5 days
Pharmacokinetic parameters of GSK962040: Cmax, Tmax, AUC(0-inf), AUC(0-t), CL/F, V/F, and half-life	3 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pre and post GSK962040 dose Gastric Residual Volume (GRV)	Duration of dosing
Pharmacokinetic parameters of paracetamol	duration of dosing
Pharmacokinetic parameters of 3OMG	duration of dosing
Plasma concentrations of motilin	duration of dosing

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Chapman MJ, Deane AM, O'Connor SL, Nguyen NQ, Fraser RJ, Richards DB, Hacquoil KE, Vasist Johnson LS, Barton ME, Dukes GE. 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 Aug 1;20(1):232. doi: 10.1186/s13054-016-1420-4.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: December 23, 2009
• First Submitted That Met QC Criteria: December 24, 2009
• First Posted (Estimate): December 25, 2009

Study Record Updates

• Last Update Posted (Estimate): January 30, 2017
• Last Update Submitted That Met QC Criteria: January 27, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: tolerability; pharmacokinetics; GSK962040; pharmacodynamics; critically ill patients; single dose; gut motility; 13C octanoic acid breath test; gastric emtpying
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neurologic Manifestations; Disease Attributes; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Critical Illness; Gastroparesis
• Other Study ID Numbers: 112571

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 112571
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 112571
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 112571
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 112571
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 112571
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 112571
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 112571
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register