Ignite Creation Date:
2024-05-06 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 12:45 PM
Study NCT ID:
NCT03513393
Status:
COMPLETED
Last Update Posted:
2020-10-19
First Post:
2018-04-18
Brief Title:
Influence of Cola on the Absorption of the HCV Agent Velpatasvir in Combination With PPI Omeprazole
Sponsor:
Radboud University Medical Center
Organization:
Radboud University Medical Center
Study Overview
Official Title:
Influence of the Acidic Beverage Cola on the Absorption of the HCV Agent Velpatasvir in Healthy Volunteers Being Treated With the Proton Pump Inhibitor Omeprazole
Status:
COMPLETED
Status Verified Date:
2019-01
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:
COPA
Brief Summary:
Epclusa is a pan-genotypic once-daily tablet for the treatment of chronic hepatitis C virus HCV infection containing the NS5B- polymerase inhibitor sofosbuvir SOF nucleotide analogue 400 mg and the NS5A inhibitor velpatasvir VEL 100 mg
Velpatasvir has pH dependent absorption At higher pH the solubility of velpatasvir decreases It has been shown that in subjects treated with proton pump inhibitors PPIs such as omeprazole the absorption of velpatasvir is reduced by 26-56 depending on the dose of omeprazole concomitant food intake and timingsequence of velpatasvir vs omeprazole intake As a result concomitant intake of PPIs with velpatasvir is not recommended
For a number of reasons the prohibition of PPI use with velpatasvir is a clinically relevant problem First PPI use is highly frequent in the HCV-infected subject population with prevalences reported up to 40 Second PPIs are available as over-the-counter medications and thus can be used by subjects without informing their physician Third although HCV therapy is generally well tolerated gastro-intestinal symptoms such as abdominal pain and nausea are frequently reported which my lead to PPI use
One solution of this problem could be the use of other acid-reducing agents such as H2-receptor antagonists or antacids In general they have a less pronounced effect on intragastric pH and are considered less effective than PPIs by many patients and physicians
A second solution would be the choice of another HCV agent or combination that is not dependent on low gastric pH for its absorption such as daclatasvir Daclatasvir however is not a pan-genotypic HCV agent and may be less effective against GT 2 and 3 infections than velpatasvir Second not all subjects have access to daclatasvir depending on health insurance company or region where they live
A third solution and the focus of this COPA study is to add a glass of the acidic beverage cola at the time of velpatasvir administration in subjects concurrently treated with PPIs This intervention has been shown to be effective for a number of drugs from other therapeutic classes who all have in common a reduced solubility and thus reduced absorption at higher intragastric pH namely erlotinib itraconazole ketoconazole
The advantages of this approach are 1 only a temporary decrease in gastric pH at the time of cola intake the rest of the day the PPI will have its therapeutic effect 2 cola is available worldwide 3 the administration of cola can be done irrespective to the timing of PPI use
Velpatasvir has pH dependent absorption At higher pH the solubility of velpatasvir decreases It has been shown that in subjects treated with proton pump inhibitors PPIs such as omeprazole the absorption of velpatasvir is reduced by 26-56 depending on the dose of omeprazole concomitant food intake and timingsequence of velpatasvir vs omeprazole intake As a result concomitant intake of PPIs with velpatasvir is not recommended
For a number of reasons the prohibition of PPI use with velpatasvir is a clinically relevant problem First PPI use is highly frequent in the HCV-infected subject population with prevalences reported up to 40 Second PPIs are available as over-the-counter medications and thus can be used by subjects without informing their physician Third although HCV therapy is generally well tolerated gastro-intestinal symptoms such as abdominal pain and nausea are frequently reported which my lead to PPI use
One solution of this problem could be the use of other acid-reducing agents such as H2-receptor antagonists or antacids In general they have a less pronounced effect on intragastric pH and are considered less effective than PPIs by many patients and physicians
A second solution would be the choice of another HCV agent or combination that is not dependent on low gastric pH for its absorption such as daclatasvir Daclatasvir however is not a pan-genotypic HCV agent and may be less effective against GT 2 and 3 infections than velpatasvir Second not all subjects have access to daclatasvir depending on health insurance company or region where they live
A third solution and the focus of this COPA study is to add a glass of the acidic beverage cola at the time of velpatasvir administration in subjects concurrently treated with PPIs This intervention has been shown to be effective for a number of drugs from other therapeutic classes who all have in common a reduced solubility and thus reduced absorption at higher intragastric pH namely erlotinib itraconazole ketoconazole
The advantages of this approach are 1 only a temporary decrease in gastric pH at the time of cola intake the rest of the day the PPI will have its therapeutic effect 2 cola is available worldwide 3 the administration of cola can be done irrespective to the timing of PPI use
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None