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FTIH to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses of GSK1322888 in Healthy Caucasian and Japanese Volunteers

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01294566
First received: February 3, 2011
Last updated: February 16, 2012
Last verified: February 2012
  Purpose

This study is the First Time In Human study for the motilin receptor agonist, GSK1322888. GSK1322888 is a potent and selective small molecule motilin receptor agonist, distinct from the motilide compound structures. The aims of this study are to assess the safety, tolerance, and pharmacokinetics of single oral doses of GSK1322888 and to identify a well-tolerated and safe dose that will accelerate gastric emptying of a 13C stable isotope-labeled test meal in healthy volunteers.

The study will include assessment of ECGs, vital signs, safety laboratory sampling, adverse events, pharmacokinetics, and the 13C-Octanoic Acid Breath Test to measure gastric emptying.


Condition Intervention Phase
Gastroparesis
Drug: GSK1322888
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo Controlled Dose Escalation Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses of GSK1322888 in Healthy Caucasian and Japanese Asian Adult Subjects

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Adverse Events following single oral doses of GSK1322888 [ Time Frame: 1 week post dose ] [ Designated as safety issue: Yes ]
    includes abnormal clincal lab values, ECGs, vital signs

  • pharmacokinetics of GSK1322888 following single, oral doses [ Time Frame: 48 h post dose ] [ Designated as safety issue: No ]
    includes AUC, Cmax, tmax, and t1/2


Secondary Outcome Measures:
  • gastric emptying of a radio-labeled test meal, as measured by the 13C-octanoic acid breath test following single oral doses of GSK1322888 [ Time Frame: 4 h ] [ Designated as safety issue: No ]
    includes gastric half emptying time, gastric emptying coefficient

  • dose/exposure response relationship for gastric emptying of a radio-labeled test meal, as measured by the 13C-octanoic acid breath test following single oral doses of GSK1322888 [ Time Frame: 48 h ] [ Designated as safety issue: No ]
    dose response of GSK1322888 on gastric emptying

  • dose proportionality following single dose administration [ Time Frame: 48 h ] [ Designated as safety issue: No ]
  • steady-state PK based on single dose data [ Time Frame: 28 h ] [ Designated as safety issue: No ]
  • accumulation based on single dose data [ Time Frame: 48 h ] [ Designated as safety issue: No ]
  • ethnicity differences in safety, tolerability, pharmacokinetics, and pharmacodynamics between volunteers of Caucasian or Japanese ethnicity [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    difference in adverse events between ethnicities


Enrollment: 17
Study Start Date: November 2010
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
GSK1322888 (1 mg, 2 mg, 5 mg, 10 mg; 6 subjects) and Placebo (32 subjects)
Drug: GSK1322888
1 mg, 5 mg or 25 mg capsule
Drug: Placebo
matching placebo capsules
Experimental: Cohort 2
GSK1322888 (20 mg, 40 mg, 80 mg, and dose to be determined; 6 subjects) and Placebot (2 subjects)
Drug: GSK1322888
1 mg, 5 mg or 25 mg capsule
Drug: Placebo
matching placebo capsules

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • AST, ALT, alkaline phosphatase and bilirubin < or =1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Healthy as determined by a responsible and experienced physician
  • Male or female between 18 (20 for Japanese) and 65 years of age inclusive
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods
  • Body weight > or = 50 kg and BMI within the range 18.5 - 29.9 kg/m2 (inclusive).
  • Capable of giving written informed consent
  • Average QTc, QTcB or QTcF < 430 msec.
  • For Japanese subjects Japanese ancestry defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese.

Exclusion Criteria:

  • Hepatitis B or Hepatitis C positive
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A positive pre-study drug/alcohol screen.
  • HIV positive
  • History of regular alcohol consumption within 6 months of the study
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) prior to the first dose of study medication
  • History of sensitivity to any of the study medications, or components thereof
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Pregnant females
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  • Regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • 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 first dose of study medication.
  • Subjects will be screened such that those subjects exhibiting rapid gastric emptying rates (t½b < 75 min) will be excluded
  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: NCT01294566

Locations
Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01294566     History of Changes
Other Study ID Numbers: 114422
Study First Received: February 3, 2011
Last Updated: February 16, 2012
Health Authority: Australia: National Health and Medical Research Council
Australia: Medicines Australia
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
safety
motilin agonist
single dose
ascending dose
GSK1322888
migrating motor complex
tolerability
FTIH
gastric emptying

Additional relevant MeSH terms:
Gastroparesis
Digestive System Diseases
Gastrointestinal Diseases
Neurologic Manifestations
Paralysis
Signs and Symptoms
Stomach Diseases

ClinicalTrials.gov processed this record on November 24, 2014