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Lack of patients who are eligible for inclusion: less patients on treatment and not using epclusa.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sofosbuvir/velpatasvir tablet | Active Comparator | Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state. |
|
| sofosbuvir/velpatasvir crushed | Experimental | Single-dose crushed sofosbuvir/velpatasvir in a fasted state. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sofosbuvir/velpatasvir tablet | Drug | Single-dose SOF/VEL as a whole tablet in a fasted state. |
|
| Measure | Description | Time Frame |
|---|---|---|
| AUC | Up to 24 hours after administration | |
| Cmax | one dosing interval after administration of SOF/VEL (up to 24 hours) |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events | During the entire conduct of the study, maximum of two weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Bonn, Germany | Bonn | Germany | ||||
| Jeroen Bosch Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32156618 | Result | van Seyen M, Samson AD, Cullen L, Eastick K, Knol H, Colbers A, Burger DM. Crushed application of sofosbuvir and velpatasvir in a patient with swallowing disorder. Int J Antimicrob Agents. 2020 Jun;55(6):105934. doi: 10.1016/j.ijantimicag.2020.105934. Epub 2020 Mar 7. No abstract available. |
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| ID | Term |
|---|---|
| D003668 | Pressure Ulcer |
| ID | Term |
|---|---|
| D012883 | Skin Ulcer |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000611331 | sofosbuvir-velpatasvir drug combination |
| D000069474 | Sofosbuvir |
| ID | Term |
|---|---|
| D014542 | Uridine Monophosphate |
| D014500 | Uracil Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
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Bio-equivalence Study
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| sofosbuvir/velpatasvir crushed | Drug | Single-dose crushed SOF/VEL in a fasted state. |
|
| 's-Hertogenbosch |
| Netherlands |
| Radboud university medical center Department of GI tract | Nijmegen | Netherlands |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |