Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet

Study Overview
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Brief Summary
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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. For patients with swallowing difficulties, administration of whole tablets can be problematic. In addition, HCV patients that are hospitalized (at intensive care units) due to severe illness (co-infections/ liver failure) might not be able to swallow medication. Therefore it is useful to know whether it is possible to administer SOF/VEL through a different route, like a feeding tube. In daily practice, information about the safety and efficacy of crushed tablets is lacking which might result in interruption or discontinuation of expensive HCV therapy. However, it is not recommended to interrupt treatment because there is no evidence about the efficacy of the therapy after discontinuation (and restart). Currently, patients and healthcare professionals are crushing SOF/VEL tablets without information about efficacy and safety. Depending on the biopharmaceutical characteristics of a drug formulation, crushing tablets can lead to altered pharmacokinetics of drugs. It is important to know whether pharmacokinetic parameters are influenced by crushing of tablets; both a decrease and an increase in exposure may occur. A decrease of the plasma concentrations of SOF and/or VEL potentially reduces the therapeutic effect of the drugs. Higher doses or switching to other HCV-drugs might be needed. In contrast, in case a higher Cmax,ss and/or exposure occurs there might be an increased risk of toxicity. As a result, crushing the drug is a contra-indication based on the available data. Therefore this study will be conducted to investigate whether a crushed SOF/VEL tablet is bioequivalent to SOF/VEL as a whole tablet.

Official Title
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Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet

Conditions
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HCV

Intervention / Treatment
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* Drug: sofosbuvir/velpatasvir tablet
* Drug: sofosbuvir/velpatasvir crushed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with SOF/VEL treatment for the treatment of chronic HCV genotype 1 through 6. Patient is at least 18 at the day of screening. Patient is able and willing to sign the Informed Consent Form. Patient is able and willing to follow protocol requirements. Exclusion Criteria: Pregnant female (as confirmed by an hCG urine test performed at screening) or breast-feeding female. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. Inability to understand the nature and extent of the study and the procedures required. Clinically relevant low hemoglobin concentration at screening judged by the patient's own hepatologist.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Bio-equivalence Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: sofosbuvir/velpatasvir tablet<br>Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state. | Drug: sofosbuvir/velpatasvir tablet<br>* Single-dose SOF/VEL as a whole tablet in a fasted state.<br>|
| Experimental: sofosbuvir/velpatasvir crushed<br>Single-dose crushed sofosbuvir/velpatasvir in a fasted state. | Drug: sofosbuvir/velpatasvir crushed<br>* Single-dose crushed SOF/VEL in a fasted state.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC |  | Up to 24 hours after administration | 
| Cmax |  | one dosing interval after administration of SOF/VEL (up to 24 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | During the entire conduct of the study, maximum of two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epclusa, Pharmacokinetics, Crushing