Clinical trial NCT01294566: FTIH to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses of GSK1322888 in Healthy Caucasian and Japanese Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastroparesis
Keywords: safety
motilin agonist
single dose
ascending dose
GSK1322888
migrating motor complex
tolerability
FTIH
gastric emptying
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-02-11
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Adverse Events following single oral doses of GSK1322888
timeFrame: 1 week post dose
measure: pharmacokinetics of GSK1322888 following single, oral doses
timeFrame: 48 h post dose
Secondary outcomes:
measure: gastric emptying of a radio-labeled test meal, as measured by the 13C-octanoic acid breath test following single oral doses of GSK1322888
timeFrame: 4 h
measure: 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
timeFrame: 48 h
measure: dose proportionality following single dose administration
timeFrame: 48 h
measure: steady-state PK based on single dose data
timeFrame: 28 h
measure: accumulation based on single dose data
timeFrame: 48 h
measure: ethnicity differences in safety, tolerability, pharmacokinetics, and pharmacodynamics between volunteers of Caucasian or Japanese ethnicity
timeFrame: 1 week
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: