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

HCV Clinical Trial

— CRUSADE-1  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03389061
• Other study ID #: UMCN-AKF 16.06
• Status: Withdrawn
• Phase: Phase 4
• Start date: April 1, 2018
• Est. completion date: March 22, 2019

Study information

• Verified date: December 2020
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 22, 2019
• Est. primary completion date: March 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Crush Injuries
• HCV

Intervention

Drug:
• sofosbuvir/velpatasvir tablet
Single-dose SOF/VEL as a whole tablet in a fasted state.
• sofosbuvir/velpatasvir crushed
Single-dose crushed SOF/VEL in a fasted state.

Locations

Country	Name	City	State
Germany	University of Bonn, Germany	Bonn
Netherlands	Jeroen Bosch Hospital	's-Hertogenbosch
Netherlands	Radboud university medical center Department of GI tract	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Countries where clinical trial is conducted

Germany,  Netherlands, 

References & Publications (1)

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. Epu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC		Up to 24 hours after administration
Primary	Cmax		one dosing interval after administration of SOF/VEL (up to 24 hours)
Secondary	Adverse events		During the entire conduct of the study, maximum of two weeks