Influence of Cola on the Absorption of the HCV Agent Velpatasvir in Combination With PPI Omeprazole.
Status:
Completed
Trial end date:
2018-12-01
Target enrollment:
Participant gender:
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 timing/sequence 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.