Hepatitis CPhase 1COPANCT03513393
Influence of Cola on the Absorption of the HCV Agent Velpatasvir in Combination With PPI Omeprazole.
A Phase 1 study testing velpatasvir in people with Hepatitis C and Swallowing Disorder, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C, Swallowing Disorder
- What is being tested?
- velpatasvir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Aug 2018to 1 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subject is at least 18 and not older than 55 years at screening.
- Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to Day 1.
- Subject weighs at least 40 kg.
- Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- Subject is in good age-appropriate health condition as established by medical history, physical examination, and electrocardiography, results of biochemistry, hematology and urinalysis testing within 4 weeks prior to Day 1. Results of biochemistry, hematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded.
- Subject has a normal blood pressure and pulse rate, according to the Investigator's judgment.
Who cannot join
- Creatinine clearance below 60 mL/min.
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Positive hepatitis B or C test
- Pregnant female (as confirmed by an hCG test performed less than 4 weeks before day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contra-ception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study.
- Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen (max 2 gram/day).
- Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal and hepatic disorders (clinically relevant increased ALAT/ASAT or hyperbilirubinemia), hormonal disorders (especially diabetes mellitus), coagulation disorders.
Show all 13Show fewer
- Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- History of or current abuse of drugs, alcohol or solvents (positive drugs of abuse test).
- Inability to understand the nature and extent of the study and the procedures required.
- Participation in a drug study within 60 days prior to Day 1.
- Donation of blood within 60 days prior to Day 1.
- Febrile illness within 3 days before Day 1.
- Co-worker of Radboud university medical center.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud university medical Center
Nijmegen, Gelderland, 6525 GA
About this study
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.
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.
Read more
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.
- Conditions
- Hepatitis C, Swallowing Disorder
- Being tested
- velpatasvir
- Keywords
- velpatasvir, cola, omeprazole, proton pump inhibitors
- Medical subject headings
- Hepatitis C, Deglutition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
velpatasvirDrug
Also called Omeprazole, Coca Cola Classic 250ml
Test 1
velpatasvirDrug
Also called Omeprazole, water 250ml
Test 2
velpatasvirDrug
Reference
| Study group | Role | What they receive |
|---|---|---|
| A: Epclusa + omeprazole + Coca Cola (test 1) | Experimental | 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). Receives: Drug: velpatasvir |
| B: Epclusa + omeprazole + water (test 2) | Experimental | Day 8 - 13: 40mg omeprazole QD; on Day 12 a single-dose of SOF/VEL is administered (test 2). Receives: Drug: velpatasvir |
| C: Epclusa + water (Reference) | Active comparator | Day 15 - 21: no treatment with omeprazole; on Day 19 a single-dose of SOF/VEL is administered (reference). Receives: Drug: velpatasvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bioequivalence AUC0-inf
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.
Measured: 21 days
Secondary outcomes (3)
Safety and tolerability of Epclusa in healthy volunteers
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).
Measured: 21 days
Bioequivalence (Cmax)
Determination of velpatasvir Cmax by noncompartmental analysis.
Measured: 21 days
Bioequivalence AUC0-48h
Determination of velpatasvir AUC0-48h by noncompartmental analysis.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2018
- Study start1 Aug 2018
- Primary completion1 Dec 2018
- Study completion1 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- 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)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03513393
- Sponsor's protocol ID
- UMCN-AKF 17.02
- Acronym
- COPA
- Status last verified
- Jan 2019
- First submitted
- 18 Apr 2018
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
van Seyen M, Colbers A, Abbink EJ, Drenth JPH, Burger DM. Concomitant Intake of Coca-Cola to Manage the Drug-Drug Interaction Between Velpatasvir and Omeprazole Studied in Healthy Volunteers. Clin Pharmacol Ther. 2019 Nov;106(5):1093-1098. doi: 10.1002/cpt.1569. Epub 2019 Aug 18.
PubMed 31313296
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03513393
- Acronym / sponsor ID
- COPA / UMCN-AKF 17.02
- Conditions
- Hepatitis C, Swallowing Disorder
- Keywords
- velpatasvir, cola, omeprazole, proton pump inhibitors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 1 Dec 2018 (actual)
- Study completion
- 1 Dec 2018 (actual)
- First posted
- 1 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- An open-label, 3-period, single-centre, phase-I, multi PPI dose, single velpatasvir dose trial in 12 healthy volunteers.
| Arm | Type | Receives |
|---|---|---|
| A: Epclusa + omeprazole + Coca Cola (test 1) | Experimental | Drug: velpatasvirDay 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). |
| B: Epclusa + omeprazole + water (test 2) | Experimental | Drug: velpatasvirDay 8 - 13: 40mg omeprazole QD; on Day 12 a single-dose of SOF/VEL is administered (test 2). |
| C: Epclusa + water (Reference) | Active comparator | Drug: velpatasvirDay 15 - 21: no treatment with omeprazole; on Day 19 a single-dose of SOF/VEL is administered (reference). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Subject is at least 18 and not older than 55 years at screening.
- Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to Day 1.
- Subject weighs at least 40 kg.
- Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
Key exclusion criteria (13 listed)
- Creatinine clearance below 60 mL/min.
- Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- Positive hepatitis B or C test
- Pregnant female (as confirmed by an hCG test performed less than 4 weeks before day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contra-ception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study.
- Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen (max 2 gram/day).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| velpatasvirAlso: Omeprazole, Coca Cola Classic 250mlTest 1 | Drug | A: Epclusa + omeprazole + Coca Cola (test 1) |
| velpatasvirAlso: Omeprazole, water 250mlTest 2 | Drug | B: Epclusa + omeprazole + water (test 2) |
| velpatasvirReference | Drug | C: Epclusa + water (Reference) |
Primary outcome
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.
3 secondary outcomes
Safety and tolerability of Epclusa in healthy volunteers
Time frame: 21 days
Bioequivalence (Cmax)
Time frame: 21 days
Bioequivalence AUC0-48h
Time frame: 21 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Results publication: PubMed 31313296van Seyen M, Colbers A, Abbink EJ, Drenth JPH, Burger DM. Concomitant Intake of Coca-Cola to Manage the Drug-Drug Interaction Between Velpatasvir and Omeprazole Studied in Healthy Volunteers. Clin Pharmacol Ther. 2019 Nov;106(5):1093-1098. doi: 10.1002/cpt.1569. Epub 2019 Aug 18.
- paperLink provided by the sponsor.
Related trials for Hepatitis C
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Not yet recruitingObservational study
Elimination of Hepatitis C Virus Among Users of Substances
Hepatitis C in Substance Users
Not yet recruiting
Clinical Study to Evaluate the Performance of the INSTI® HCV Antibody Test for CLIA-Waived Use
HCV Infection
Not yet recruiting
Study to Evaluate the Performance of the INSTI® HCV Antibody Test for Point-of-Care Use in Individuals at Risk for HCV Infection or Presenting With Signs or Symptoms of HCV Infection
HCV Infection
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing velpatasvir in people with Hepatitis C and Swallowing Disorder, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bioequivalence AUC0-inf (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03513393, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.