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

Gastroparesis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01294566
• Other study ID #: 114422
• Status: Completed
• Phase: Phase 1
• First received: February 3, 2011
• Last updated: June 27, 2017
• Start date: November 29, 2010
• Est. completion date: March 23, 2011

Study information

• Verified date: June 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: March 23, 2011
• Est. primary completion date: March 23, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Gastroparesis

Intervention

Drug:
• GSK1322888
1 mg, 5 mg or 25 mg capsule
• Placebo
matching placebo capsules

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Randwick	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events following single oral doses of GSK1322888	includes abnormal clincal lab values, ECGs, vital signs	1 week post dose
Primary	pharmacokinetics of GSK1322888 following single, oral doses	includes AUC, Cmax, tmax, and t1/2	48 h post dose
Secondary	gastric emptying of a radio-labeled test meal, as measured by the 13C-octanoic acid breath test following single oral doses of GSK1322888	includes gastric half emptying time, gastric emptying coefficient	4 h
Secondary	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	dose response of GSK1322888 on gastric emptying	48 h
Secondary	dose proportionality following single dose administration		48 h
Secondary	steady-state PK based on single dose data		28 h
Secondary	accumulation based on single dose data		48 h
Secondary	ethnicity differences in safety, tolerability, pharmacokinetics, and pharmacodynamics between volunteers of Caucasian or Japanese ethnicity	difference in adverse events between ethnicities	1 week

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
•   Results for study 114422 can be found on the GSK Clinical Study Register.