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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gastroparesis

Intervention / Treatment
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* Drug: GSK1322888
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>GSK1322888 (1 mg, 2 mg, 5 mg, 10 mg; 6 subjects) and Placebo (32 subjects) | Drug: GSK1322888<br>* 1 mg, 5 mg or 25 mg capsule<br>Drug: Placebo<br>* matching placebo capsules<br>|
| Experimental: Cohort 2<br>GSK1322888 (20 mg, 40 mg, 80 mg, and dose to be determined; 6 subjects) and Placebot (2 subjects) | Drug: GSK1322888<br>* 1 mg, 5 mg or 25 mg capsule<br>Drug: Placebo<br>* matching placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events following single oral doses of GSK1322888 | includes abnormal clincal lab values, ECGs, vital signs | 1 week post dose | 
| pharmacokinetics of GSK1322888 following single, oral doses | includes AUC, Cmax, tmax, and t1/2 | 48 h post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| dose proportionality following single dose administration |  | 48 h | 
| steady-state PK based on single dose data |  | 28 h | 
| accumulation based on single dose data |  | 48 h | 
| ethnicity differences in safety, tolerability, pharmacokinetics, and pharmacodynamics between volunteers of Caucasian or Japanese ethnicity | difference in adverse events between ethnicities | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, motilin agonist, single dose, ascending dose, GSK1322888, migrating motor complex, tolerability, FTIH, gastric emptying