Last updated: 11/07/2018 08:03:38
Effect of GSK962040 on oesophageal function
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A double blind randomised placebo controlled two way cross over study to determine the effect of GSK962040 on oesophageal function and gastric emptying in healthy male volunteers.
Trial description: GSK962040 is a selective non-peptide motilin receptor agonist which is in development for the treatment of conditions associated with slow rates of gastric emptying. Single ascending doses (1 to 150 mg), and 14-days repeated doses (10 to 125 mg daily) have been investigated in two randomized, placebo-controlled trials. Results show that these doses were well tolerated with few mild to moderate adverse events (AE), and no clinically significant abnormal vital sign measurements, ECG changes or abnormal clinical laboratory findings. GSK962040 exhibited predictable PK with and without food. The mean within subject time for half a [13C]-containing meal to empty from the stomach (GE t½) decreased by 22-43% from placebo with GSK962040 50-150 mg single doses, and shortening of gastric emptying was confirmed at doses of 50 mg and above in the repeat dose study. Several studies have shown that motilin agonists increase lower oesophageal sphincter (LOS) pressure and have various dose dependent effects on oesophageal peristaltic amplitudes and propulsive contractions in both healthy volunteers and patients with gastro-oesophageal reflux disease (GORD). The purpose of the present study is to examine the effect of GSK962040 on oesophageal function, using techniques such as high resolution oesophageal manometry, and pH/gastric transit using a wireless motility capsule.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from baseline lower oesophageal sphincter (LOS) pressure (including pre and post prandial measures
Timeframe: Baseline and at 1hr30 and 2hr15mins post dose
Secondary outcomes:
Change from baseline oesophageal peristaltic amplitudes
Timeframe: baseline and at 1hr30min and 2hr15mins post dose
Change from baseline oesophageal peristaltic velocity.
Timeframe: baseline and at 1hr30min and 2hr15mins post dose
Change from baseline proximal gastric pressure.
Timeframe: baseline and at 1hr30min and 2hr15mins post dose
Total gastric emptying time.
Timeframe: absolute transit time measured using SmartPill
Number and proximal extent of reflux episodes
Timeframe: 24hrs
Safety and tolerability of GSK962040
Timeframe: baseline and at selected timepoints up to 24hrs post dose
Post prandial gastric and oesophageal pH
Timeframe: 2hr15mins post dose
Interventions:
Enrollment:
14
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Hobson R, Farmer AD, Dewit OE, O’Donnell M, Hacquoil K, Robertson D, Barton ME, Dukes GE.The effects of a camicinal, a novel motilin agonist, on gastro-oesophageal function in healthy humans-a randomized placebo controlled trial.Neurogastroenterol Motil.2015;27(11):1629-37.
Medical condition
Gastrointestinal Motility
Product
camicinal
Collaborators
Not applicable
Study date(s)
August 2010 to October 2010
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- 1.Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- 2.Male between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- 1.A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- 2.A positive test for HIV antibody.
Inclusion and exclusion criteria
Inclusion criteria:
- 1.Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. 2.Male between 18 and 65 years of age inclusive, at the time of signing the informed consent. 3.AST, ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 4.Subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication through at least 5 days following the dose of GSK962040. 5.Body weight = 50 kg and BMI within the range 18.5-29.9 kg/m2 (inclusive). 6.Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 7. QTcB or QTcF < 450 msec or QTc<480msec in subjects with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period.
Exclusion criteria:
- 1.A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. 2.A positive test for HIV antibody. 3.Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 4.History of cholecystectomy or biliary tract disease. 5.History of major gastrointestinal surgical procedure. 6.History of bowel surgery within the 3 months preceeding screening 7.History of strictures or adhesions following surgery. 8.History of, or current clinically significant gastrointestinal transit condition, ie. Passing of < 1 bowel movement per 48hr period. 9.A positive pre-study drug/alcohol screen. 10.A previous reaction or allergy to local anesthetic gels or sprays. 11.History of regular alcohol consumption within 6 months of the study defined as: -an average weekly intake of >21 units. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits. 12.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: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 13.Smoking history that includes regular use of tobacco or nicotine-containing products within 6 months prior to screening. 14.Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 15.Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. 16.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. 17.Where participation in the study would result in donation of blood or blood products in excess of 500mL within a 90 day period. 18.Unwillingness or inability to follow the procedures outlined in the protocol. 19.Subject is mentally or legally incapacitated. 20.Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the dose of study medication.
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2010-22-10
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
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Additional information
Results for study 114639 can be found on the GSK Clinical Study Register.
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