NCT03513393: COPA

Influence of Cola on the Absorption of the HCV Agent Velpatasvir in Combination With PPI Omeprazole.

Completed Phase 1 Last updated 19 October 2020

What this trial tests

Phase 1 trial testing velpatasvir in Hepatitis C in 11 participants. Completed in 1 December 2018.

Timeline

1 August 2018

Primary endpoint
1 December 2018

1 December 2018

Quick facts

Lead sponsor	Radboud University Medical Center
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	other
Enrollment	11
Start date	1 August 2018
Primary completion	1 December 2018
Estimated completion	1 December 2018
Sites	1 location across Netherlands

Drugs / interventions tested

• velpatasvir — full drug profile →
• velpatasvir — full drug profile →
• velpatasvir — full drug profile →

Conditions studied

• Hepatitis C — all drugs for Hepatitis C →
• Swallowing Disorder — all drugs for Swallowing Disorder →

Sponsor

Radboud University Medical Center

Who can join

Adults 18 to 55, any sex, with Hepatitis C or Swallowing Disorder. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Progress, evolving therapeutic/diagnostic approaches, and challenges in the management of hepatitis C virus infections.
   Meshram RJ, Kathwate GH, Gacche RN. · · 2022 · cited 9× · PMID 35089390 · DOI 10.1007/s00705-022-05375-0
2. Concomitant Intake of Coca-Cola to Manage the Drug-Drug Interaction Between Velpatasvir and Omeprazole Studied in Healthy Volunteers.
   van Seyen M, Colbers A, Abbink EJ, Drenth JPH, et al · · 2019 · cited 6× · PMID 31313296 · DOI 10.1002/cpt.1569