Ignite Creation Date:
2024-05-05 @ 11:56 PM
Last Modification Date:
2024-10-26 @ 10:42 AM
Study NCT ID:
NCT01453478
Status:
COMPLETED
Last Update Posted:
2017-06-12
First Post:
2011-10-13
Brief Title:
A Study to Look at How GSK1325756 is Taken up by the Body When Given by Mouth When Stomach Acid is Reduced
Sponsor:
GlaxoSmithKline
Organization:
GlaxoSmithKline
Study Overview
Official Title:
A Single Centre 5-Period Randomized Study To Evaluate The Relative Bioavailability Of An Immediate Release Tablet Formulation And Prototype Bioenhanced Formulations Of GSK1325756 In Healthy Elderly Subjects During Suppression Of Gastric Acid Secretion
Status:
COMPLETED
Status Verified Date:
2017-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase I study to assess the combined effects of food and suppression of gastric acid secretion on the relative bioavailability of an immediate release IR tablet formulation and prototype bioenhanced formulations of GSK1325756 an oral interleukin 8 receptor IL8R also known as CXCR2 antagonist The objectives are to understand if the co-administration of food enhances absorption and the inter-subject variability for the current GSK1325756 IR tablet under fed state proton pump inhibitor PPI conditions and secondly to assess whether two proposed bioenhanced formulations offer any improvement over the current GSK1325756 IR formulation under PPI conditions
This open-label randomized 5-period crossover study will be completed in a single cohort of subjects with an interim analysis after completion of Treatment Period 4 During Treatment Periods 1 to 4 subjects will be randomized to receive GSK1325756 50 mg IR in the fed state GSK1325756 50 mg IR in the fasted state GSK1325756 Bioenhanced Formulation 1 in the fasted state and GSK1325756 Bioenhanced Formulation 2 in the fasted state Progression to Treatment Period 5 and the choice of bioenhanced formulation for dosing in this treatment period will be dependent on the findings of an interim analysis of the pharmacokinetic profile and relative bioavailability of each formulation following completion of Treatment Periods 1 to 4 In Treatment Period 5 subjects will receive the selected GSK1325756 bioenhanced formulation in the fed state
This open-label randomized 5-period crossover study will be completed in a single cohort of subjects with an interim analysis after completion of Treatment Period 4 During Treatment Periods 1 to 4 subjects will be randomized to receive GSK1325756 50 mg IR in the fed state GSK1325756 50 mg IR in the fasted state GSK1325756 Bioenhanced Formulation 1 in the fasted state and GSK1325756 Bioenhanced Formulation 2 in the fasted state Progression to Treatment Period 5 and the choice of bioenhanced formulation for dosing in this treatment period will be dependent on the findings of an interim analysis of the pharmacokinetic profile and relative bioavailability of each formulation following completion of Treatment Periods 1 to 4 In Treatment Period 5 subjects will receive the selected GSK1325756 bioenhanced formulation in the fed state
Detailed Description:
The primary objective of this study is to evaluate the relative bioavailability including the inter-subject variability of the immediate release IR tablet used for the previous Phase I studies and 2 prototype bioenhanced tablet formulations of GSK1325756 in healthy elderly male and female subjects under fed and fasted states during suppression of gastric acid secretion concomitant omeprazole 20 mg once daily QD Secondary objectives include provision of information on the oral pharmacokinetic PK of GSK1325756 in the elderly under different dosing conditions during suppression of gastric acid secretion and additional safety and tolerability information for oral administration of GSK1325756 in elderly subjects
The current study will provide an understanding of the PK of three formulations of GSK1325756 during gastric acid suppression in a population of 65 to 80 year old healthy adult subjects The effect of food on the PK of each GSK1325756 formulation will also be addressed in this population The outcome of this study is likely to guide selection of the most appropriate formulationdosing regimen for future studies
The completed clinical studies demonstrated that to minimize inter-subject variability of the exposure to GSK1325756 the current formulation needs to be administered with food particularly in elderly subjects This does not preclude development of the current formulation but is not ideal particularly if twice daily administration is needed in chronic obstructive pulmonary disease COPD patients and for elderly subjects in which food intake can be variable In addition the inter-subject variability in exposure with the current formulation when given with omeprazole in the fasted state is not acceptable This is likely due to the need for a low pH acid level pH 2 gastric environment particularly in the fasted state to allow for sufficient solubilization of the GSK1325756 prior to transport to the small intestine where it is absorbed Thus this study is being conducted for the following reasons 1 to determine if the current formulation results in acceptable exposure and inter-subject variability if given with food in subjects in which gastric acid secretion is suppressed with omeprazole and 2 to determine if a bio-enhanced formulation can provide an acceptable exposure profile and acceptable inter-subject variability in the fasted state in subjects in which gastric acid is suppressed This information will be important in helping to determine the appropriate formulation and dosing regimen for progression to studies in COPD patients
The current study will provide an understanding of the PK of three formulations of GSK1325756 during gastric acid suppression in a population of 65 to 80 year old healthy adult subjects The effect of food on the PK of each GSK1325756 formulation will also be addressed in this population The outcome of this study is likely to guide selection of the most appropriate formulationdosing regimen for future studies
The completed clinical studies demonstrated that to minimize inter-subject variability of the exposure to GSK1325756 the current formulation needs to be administered with food particularly in elderly subjects This does not preclude development of the current formulation but is not ideal particularly if twice daily administration is needed in chronic obstructive pulmonary disease COPD patients and for elderly subjects in which food intake can be variable In addition the inter-subject variability in exposure with the current formulation when given with omeprazole in the fasted state is not acceptable This is likely due to the need for a low pH acid level pH 2 gastric environment particularly in the fasted state to allow for sufficient solubilization of the GSK1325756 prior to transport to the small intestine where it is absorbed Thus this study is being conducted for the following reasons 1 to determine if the current formulation results in acceptable exposure and inter-subject variability if given with food in subjects in which gastric acid secretion is suppressed with omeprazole and 2 to determine if a bio-enhanced formulation can provide an acceptable exposure profile and acceptable inter-subject variability in the fasted state in subjects in which gastric acid is suppressed This information will be important in helping to determine the appropriate formulation and dosing regimen for progression to studies in COPD patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None