Effect of GSK962040 on Oesophageal Function

NCT01366560 | Completed Phase 1

• 1 other identifier: 114639
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastrointestinal Motility

Outcome Measures

Primary Outcomes (1)

• Change from baseline lower oesophageal sphincter (LOS) pressure (including pre and post prandial measures

  Baseline and at 1hr30 and 2hr15mins post dose

Secondary Outcomes (7)

• Change from baseline oesophageal peristaltic amplitudes

  baseline and at 1hr30min and 2hr15mins post dose

• Change from baseline oesophageal peristaltic velocity.

  baseline and at 1hr30min and 2hr15mins post dose

• Change from baseline proximal gastric pressure.

  baseline and at 1hr30min and 2hr15mins post dose

• Total gastric emptying time.

  absolute transit time measured using SmartPill

• Number and proximal extent of reflux episodes

  24hrs

Study Arms (2)

GSK962040

EXPERIMENTAL

The subjects will be administered GSK962040 125 mg tablet as a single dose on Day 1 of study treatment visit. After 2 hours, the subjects will be administered wireless motility capsule. The subjects will be observed for expulsion of WMC in stool. Each subject will attend the clinical unit for two study treatment visits which will be separated by at least one week.

Drug: Active

Placebo

PLACEBO COMPARATOR

The subjects will be administered placebo tablet as a single dose on Day 1 of study treatment visit. After 2 hours, the subjects will be administered wireless motility capsule. The subjects will be observed for expulsion of WMC in stool. Each subject will attend the clinical unit for two study treatment visits which will be separated by at least one week.

Drug: Placebo

Interventions

Active DRUG

GSK962040 125mg

GSK962040

Placebo DRUG

Matching Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• AST, ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• 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.
• Body weight = 50 kg and BMI within the range 18.5-29.9 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• 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.

You may not qualify if:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive test for HIV antibody.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of cholecystectomy or biliary tract disease.
• History of major gastrointestinal surgical procedure.
• History of bowel surgery within the 3 months preceeding screening
• History of strictures or adhesions following surgery.
• History of, or current clinically significant gastrointestinal transit condition, ie. Passing of \< 1 bowel movement per 48hr period.
• A positive pre-study drug/alcohol screen.
• A previous reaction or allergy to local anesthetic gels or sprays.
• 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.
• 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).
• Smoking history that includes regular use of tobacco or nicotine-containing products within 6 months prior to screening.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

Related Publications (1)

• Hobson R, Farmer AD, Dewit OE, O'Donnell M, Hacquoil K, Robertson D, Barton ME, Dukes GE. The effects of camicinal, a novel motilin agonist, on gastro-esophageal function in healthy humans-a randomized placebo controlled trial. Neurogastroenterol Motil. 2015 Nov;27(11):1629-37. doi: 10.1111/nmo.12663. Epub 2015 Sep 8.

  PMID: 26348542 DERIVED

Related Links

• Results for study 114639 can be found on the GSK Clinical Study Register.

MeSH Terms

Interventions

Exercise

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2011
• First Posted: June 6, 2011
• Study Start: August 31, 2010
• Primary Completion: October 22, 2010
• Study Completion: October 22, 2010
• Last Updated: July 18, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)