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

Gastroparesis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01039805
• Other study ID #: 112571
• Status: Completed
• Phase: Phase 2
• First received: December 23, 2009
• Last updated: January 27, 2017
• Start date: December 2009
• Est. completion date: July 2011

Study information

• Verified date: January 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Critical Illness
• Gastroparesis

Intervention

Drug:
• GSK962040 (50 mg)
Cohort 1 = 50 mg
• Placebo
matching placebo
• GSK962040 (75 mg)
Cohort 2 = 75 mg

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Adelaide	South Australia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gastric emptying		3 days
Primary	Safety and tolerability of GSK962040		5 days
Primary	Pharmacokinetic parameters of GSK962040: Cmax, Tmax, AUC(0-inf), AUC(0-t), CL/F, V/F, and half-life		3 days
Secondary	Pre and post GSK962040 dose Gastric Residual Volume (GRV)		Duration of dosing
Secondary	Pharmacokinetic parameters of paracetamol		duration of dosing
Secondary	Pharmacokinetic parameters of 3OMG		duration of dosing
Secondary	Plasma concentrations of motilin		duration of dosing

External Links

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