Ignite Creation Date:
2024-05-05 @ 11:47 PM
Last Modification Date:
2024-10-26 @ 10:39 AM
Study NCT ID:
NCT01411111
Status:
COMPLETED
Last Update Posted:
2017-07-25
First Post:
2011-04-14
Brief Title:
A Repeat Dose Study to Investigate the Interaction of GSK2190915 on the Pharmacokinetics of Rosuvastatin
Sponsor:
GlaxoSmithKline
Organization:
GlaxoSmithKline
Study Overview
Official Title:
An Open Label Sequential Single Cohort Repeat Dose Study to Investigate the Potential Interaction of GSK2190915 on the Pharmacokinetics of Rosuvastatin in Healthy Adult Subjects
Status:
COMPLETED
Status Verified Date:
2017-07
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:
Leukotrienes are potent inflammatory molecules produced mainly by mast cells eosinophils monocytesmacrophage and neutrophils in response to allergic or inflammatory stimuli GSK2190915 is a high affinity 5-lipoxygenase-activating protein FLAP inhibitor that attenuates the production of leukotrienes through the blockage of the first committed step in the leukotriene pathway 5 lipoxygenase 5-LO activation
GSK2190915 has been shown to be an in vitro inhibitor of human organic anion transporting polypeptides 1B1 and 1B3 OATP1B1 and OATP1B3 hence there is a potential for a pharmacokinetic drug-drug interaction with OATP1 B1 substrates such as the anti-lipidemic rosuvastatin
This study will evaluate the effect of repeat oral dosing of GSK2190915 30milligram mg and 100mg on the steady-state pharmacokinetics PK of rosuvastatin 10 mg In addition the study will evaluate the safety and tolerability of this combination when co-administered to healthy adult volunteers in two cohorts
GSK2190915 has been shown to be an in vitro inhibitor of human organic anion transporting polypeptides 1B1 and 1B3 OATP1B1 and OATP1B3 hence there is a potential for a pharmacokinetic drug-drug interaction with OATP1 B1 substrates such as the anti-lipidemic rosuvastatin
This study will evaluate the effect of repeat oral dosing of GSK2190915 30milligram mg and 100mg on the steady-state pharmacokinetics PK of rosuvastatin 10 mg In addition the study will evaluate the safety and tolerability of this combination when co-administered to healthy adult volunteers in two cohorts
Detailed Description:
GSK2190915 is a high affinity 5-lipoxygenase-activating protein FLAP inhibitor that attenuates the production of leukotrienes through the blockage of the first committed step in the leukotriene pathway 5 lipoxygenase 5-LO activation Leukotrienes are potent inflammatory molecules produced mainly by mast cells eosinophils monocytesmacrophage and neutrophils in response to allergic or inflammatory stimuli As GSK2190915 inhibits the production of leukotriene B4 and cysteinyl leukotrienes it has strong potential utility in the treatment of asthma and Chronic Obstructive Pulmonary Disease COPD The organic anion transporting polypeptides OATPs form a superfamily of sodium-independent transport systems that mediate the transmembrane transport of a wide range of amphipathic organic compounds Of the 11 human OATP transporters OATP1B1 and OATP1B3 are specifically expressed on the sinusoidal membrane of hepatocytes and are considered to be of particular importance for hepatic drug elimination and drug pharmacokinetics
GSK2190915 has been shown to be an inhibitor of OATP1B1 and OATP1B3 Several clinically utilised drugs have been identified as substrates of OATP transporters including rosuvastatin - a member of the statin group of anti-lipidemics
As the target patient population for GSK2190915 may overlap with that for statins such as rosuvastatin it is important to evaluate any potential effects of GSK2190915 on the pharmacokinetics of a statin known to undergo hepatic elimination via OATP1B11B3 This study will evaluate the effect of repeat oral dosing of GSK2190915 on the steady-state pharmacokinetics of rosuvastatin In addition the study will evaluate the safety and tolerability of this combination when co-administered to healthy adult volunteers
Two dose levels of GSK2190915 will be investigated 30mg and 100mg once daily for 7 days The rosuvastatin dose selected for this study is 10mg which allows for up to a 4 times increase in systemic exposure if there is a pharmacokinetic interaction
The study will be an open label single-sequence study in two cohorts with 2 treatment periods 28 subjects will receive rosuvastatin 10mgday for 7 days during the first treatment period following on from which 14 subjects each will receive either GSK2190915 30 mgday or GSK2190915 100mgday in combination with rosuvastatin 10mgday for the next 7 days Subjects will be followed up 7-14 days after their last dose PK samples will be obtained for both rosuvastatin and GSK2190915 during the study Safety will be evaluated via physical examinations ElectroCardioGrams ECG and vital signs
Approximately 28 healthy subjects will be enrolled such that approximately 24 subjects 12 in each of the two treatment arms complete dosing and critical assessments
GSK2190915 has been shown to be an inhibitor of OATP1B1 and OATP1B3 Several clinically utilised drugs have been identified as substrates of OATP transporters including rosuvastatin - a member of the statin group of anti-lipidemics
As the target patient population for GSK2190915 may overlap with that for statins such as rosuvastatin it is important to evaluate any potential effects of GSK2190915 on the pharmacokinetics of a statin known to undergo hepatic elimination via OATP1B11B3 This study will evaluate the effect of repeat oral dosing of GSK2190915 on the steady-state pharmacokinetics of rosuvastatin In addition the study will evaluate the safety and tolerability of this combination when co-administered to healthy adult volunteers
Two dose levels of GSK2190915 will be investigated 30mg and 100mg once daily for 7 days The rosuvastatin dose selected for this study is 10mg which allows for up to a 4 times increase in systemic exposure if there is a pharmacokinetic interaction
The study will be an open label single-sequence study in two cohorts with 2 treatment periods 28 subjects will receive rosuvastatin 10mgday for 7 days during the first treatment period following on from which 14 subjects each will receive either GSK2190915 30 mgday or GSK2190915 100mgday in combination with rosuvastatin 10mgday for the next 7 days Subjects will be followed up 7-14 days after their last dose PK samples will be obtained for both rosuvastatin and GSK2190915 during the study Safety will be evaluated via physical examinations ElectroCardioGrams ECG and vital signs
Approximately 28 healthy subjects will be enrolled such that approximately 24 subjects 12 in each of the two treatment arms complete dosing and critical assessments
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