Influence of Cola on the Absorption of the HCV Agent Velpatasvir in Combination With PPI Omeprazole. (COPA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03513393|
Recruitment Status : Not yet recruiting
First Posted : May 1, 2018
Last Update Posted : May 7, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Hepatitis C Swallowing Disorder||Drug: velpatasvir||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|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)|
|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.|
|Estimated Study Start Date :||August 1, 2018|
|Estimated Primary Completion Date :||December 1, 2018|
|Estimated Study Completion Date :||December 1, 2018|
Experimental: A: Epclusa + omeprazole + Coca Cola (test 1)
Day 1 - 6 40mg omeprazole QD; on Day 5 a single-dose of SOF/VEL with 250 mL of Coca Cola Classic is administered (test 1).
Experimental: B: Epclusa + omeprazole + water (test 2)
Day 8 - 13: 40mg omeprazole QD; on Day 12 a single-dose of SOF/VEL is administered (test 2).
Active Comparator: C: Epclusa + water (Reference)
Day 15 - 21: no treatment with omeprazole; on Day 19 a single-dose of SOF/VEL is administered (reference).
- Bioequivalence AUC0-inf [ Time Frame: 21 days ]
Determination of velpatasvir AUC0-inf by noncompartmental analysis.
Descriptive statistics for the plasma concentrations of velpatasvir at each sampling time. Descriptive statistics for each PK parameter per treatment (geometric mean + CV%).
Geometric Mean Ratios and 90% confidence intervals of pharmacokinetic parameters of A (Test 1) vs. C (Reference) and of B (Test 2) vs. C (Reference).
AUC0-inf geometric mean ratios with a 90% Cl falling entirely within the range of 0.7 to 1.43 are considered bioequivalent.
- Safety and tolerability of Epclusa in healthy volunteers [ Time Frame: 21 days ]
To evaluate the safety and tolerability of SOFA/EL tablets in healthy volunteers.
Adverse events after administration of SOFA/EL in the three interventions will be described and compared (including clinically relevant laboratory abnormalities).
- Bioequivalence (Cmax) [ Time Frame: 21 days ]Determination of velpatasvir Cmax by noncompartmental analysis.
- Bioequivalence AUC0-48h [ Time Frame: 21 days ]Determination of velpatasvir AUC0-48h by noncompartmental analysis.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03513393
|Contact: Minou van Seyen, MSc||+31 (0) 24 361 77 email@example.com|
|Contact: David Burger||+31 (0) 24 361 77 firstname.lastname@example.org|
|Radboud university medical Center||Not yet recruiting|
|Nijmegen, Gelderland, Netherlands, 6525 GA|
|Contact: David M Burger, prof. dr. +31243617744 email@example.com|
|Principal Investigator: David M Burger, prof. dr.|