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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01039805
First received: December 23, 2009
Last updated: May 2, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Gastroparesis
Drug: GSK962040 (50 mg)
Drug: Placebo
Drug: GSK962040 (75 mg)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Gastric emptying [ Time Frame: 3 days ] [ Designated as safety issue: No ]
  • Safety and tolerability of GSK962040 [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters of GSK962040: Cmax, Tmax, AUC(0-inf), AUC(0-t), CL/F, V/F, and half-life [ Time Frame: 3 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pre and post GSK962040 dose Gastric Residual Volume (GRV) [ Time Frame: Duration of dosing ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of paracetamol [ Time Frame: duration of dosing ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of 3OMG [ Time Frame: duration of dosing ] [ Designated as safety issue: No ]
  • Plasma concentrations of motilin [ Time Frame: duration of dosing ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: December 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Subjects randomized to either GSK962040 (50 mg) or placebo
Drug: GSK962040 (50 mg)
Cohort 1 = 50 mg
Drug: Placebo
matching placebo
Experimental: Cohort 2
Subjects randomized to either GSK962040 (75 mg) or placebo
Drug: Placebo
matching placebo
Drug: GSK962040 (75 mg)
Cohort 2 = 75 mg

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01039805

Locations
Australia, South Australia
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01039805     History of Changes
Other Study ID Numbers: 112571
Study First Received: December 23, 2009
Last Updated: May 2, 2013
Health Authority: Australia: Human Research Ethics Committee
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
GSK962040
13C octanoic acid breath test
pharmacokinetics
critically ill patients
gut motility
pharmacodynamics
tolerability
single dose
gastric emtpying

Additional relevant MeSH terms:
Critical Illness
Gastroparesis
Disease Attributes
Pathologic Processes
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on September 22, 2014