Hepatitis C
Conditions
Interventions
Healthy volunteers will be treated with the following treatments.
Six treatment sequences will be applied: ABC, ACB, BAC, BCA, CAB, CBA.
Treatment A 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).
Treatment B Day 8 * 13: 40mg omeprazole QD
on Day 12 a single-dose of
SOF/VEL is administered (test 2).
Treatment C Day 15 * 21: no treatment with omeprazole
on Day 19 a
single-dose of SOF/VEL is administered (reference).
All SOF/VEL doses will be given fasted to optimize the effect of cola. On study
days 5, 12, and 19 a 48h PK curve of velpatasvir will
Sponsors
Afdeling Apotheek
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Subject is at least 18 and not older than 55 years at screening. 2. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to Day 1. 3. Subject weighs at least 40 kg. 4. Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included. 5. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. 6. 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. 7. Subject has a normal blood pressure and pulse rate, according to the Investigator's judgment.
Exclusion criteria
Exclusion criteria: 1. Creatinine clearance below 60 mL/min. 2. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients. 3. Positive hepatitis B or C test 4. 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. 5. Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen (max 2 gram/day). 6. 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. 7. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. 8. History of or current abuse of drugs, alcohol or solvents (positieve drugs of abuse test). 9. Inability to understand the nature and extent of the study and the procedures required. 10. Participation in a drug study within 60 days prior to Day 1. 11. Donation of blood within 60 days prior to Day 1. 12. Febrile illness within 3 days before Day 1. 13. Co-worker of Radboud university medical center.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determination of velpatasvir pharmacokinetic parameters (AUC0-48h, AUC0-inf, Cmax, Tmax, and t1/2) by non-compartmental 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). AUC0-48h and Cmax GMR with a 90% CI falling entirely within the range of 0.7 to 1.43 are considered bioequivalent. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability of SOF/VEL tablets in healthy volunteers. Adverse events after administration of SOF/VEL in the three interventions will be described and compared (including clinically relevant laboratory abnormalities). | — |
Countries
Netherlands
Outcome results
None listed