Clinical trial NCT03389061: Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
Official title: Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: HCV
Keywords: Epclusa
Pharmacokinetics
Crushing
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2018-01-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Bio-equivalence Study
Primary purpose: OTHER

Brief 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.

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.


Eligibility criteria: Inclusion Criteria:

1. Patients with SOF/VEL treatment for the treatment of chronic HCV genotype 1 through 6.
2. Patient is at least 18 at the day of screening.
3. Patient is able and willing to sign the Informed Consent Form.
4. Patient is able and willing to follow protocol requirements.

Exclusion Criteria:

1. Pregnant female (as confirmed by an hCG urine test performed at screening) or breast-feeding female.
2. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
3. Inability to understand the nature and extent of the study and the procedures required.
4. Clinically relevant low hemoglobin concentration at screening judged by the patient's own hepatologist.

Primary outcomes:
measure: AUC
timeFrame: Up to 24 hours after administration
measure: Cmax
timeFrame: one dosing interval after administration of SOF/VEL (up to 24 hours)
Secondary outcomes:
measure: Adverse events
timeFrame: During the entire conduct of the study, maximum of two weeks
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University of Bonn, Germany
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Nijmegen
country: Netherlands
facility: Radboud university medical center Department of GI tract
Study officials:
References:
citation: 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.