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Effect of GSK962040 on Oesophageal Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01366560
First received: February 3, 2011
Last updated: July 14, 2017
Last verified: July 2017
  Purpose

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.


Condition Intervention Phase
Gastrointestinal Motility Drug: Active Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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.

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline lower oesophageal sphincter (LOS) pressure (including pre and post prandial measures [ Time Frame: Baseline and at 1hr30 and 2hr15mins post dose ]

Secondary Outcome Measures:
  • Change from baseline oesophageal peristaltic amplitudes [ Time Frame: baseline and at 1hr30min and 2hr15mins post dose ]
  • Change from baseline oesophageal peristaltic velocity. [ Time Frame: baseline and at 1hr30min and 2hr15mins post dose ]
  • Change from baseline proximal gastric pressure. [ Time Frame: baseline and at 1hr30min and 2hr15mins post dose ]
  • Total gastric emptying time. [ Time Frame: absolute transit time measured using SmartPill ]
  • Number and proximal extent of reflux episodes [ Time Frame: 24hrs ]
  • Safety and tolerability of GSK962040 [ Time Frame: baseline and at selected timepoints up to 24hrs post dose ]
    We will monitor ECG, vital signs, safety bloods and adverse events periodically throughout the study

  • Post prandial gastric and oesophageal pH [ Time Frame: 2hr15mins post dose ]

Enrollment: 14
Actual Study Start Date: August 31, 2010
Study Completion Date: October 22, 2010
Primary Completion Date: October 22, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK962040
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
GSK962040 125mg
Placebo Comparator: Placebo
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
Matching Placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  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: NCT01366560

Locations
United Kingdom
GSK Investigational Site
Cambridge, United Kingdom, CB2 2GG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 114639
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 114639
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 114639
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 114639
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 114639
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 114639
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 114639
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01366560     History of Changes
Other Study ID Numbers: 114639
Study First Received: February 3, 2011
Last Updated: July 14, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: http://

ClinicalTrials.gov processed this record on September 21, 2017