Influence of Cola on the Absorption of the HCV Agent Velpatasvir in Combination With PPI Omeprazole.
Condition: Hepatitis C; Swallowing Disorder
MeSH terms: Hepatitis C; Deglutition Disorders
Study type: Interventional
Phase: Phase 1

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.
    


Intervention name(s): velpatasvir; velpatasvir; velpatasvir
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Test 1; Test 2; Reference
Other intervention name(s): Omeprazole; Coca Cola Classic 250ml; Omeprazole; water 250ml
Intervention MeSH terms: Velpatasvir; Omeprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: An open-label, 3-period, single-centre, phase-I, multi PPI dose, single velpatasvir dose trial in 12 healthy volunteers.
Masking: None (Open Label)
Primary purpose: Other
Keywords: velpatasvir; cola; omeprazole; proton pump inhibitors