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

Phase 4

Withdrawn

• Conditions: HCV
• Interventions: Drug: sofosbuvir/velpatasvir crushed; Drug: sofosbuvir/velpatasvir tablet

• Registration Number: NCT03389061
• Lead Sponsor: Radboud University Medical Center

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-09-25
• Study First Submitted QC: 2018-01-02
• Study First Posted: 2018-01-03
• Study Start: 2018-04-01
• Primary Completion: 2019-03-22
• Study Completion: 2019-03-22
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-04
• Last Update Posted: 2020-12-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
sofosbuvir/velpatasvir crushed	sofosbuvir/velpatasvir crushed	Single-dose crushed sofosbuvir/velpatasvir in a fasted state.
sofosbuvir/velpatasvir tablet	sofosbuvir/velpatasvir tablet	Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state.

Primary Outcome Measures

Name	Time	Method
AUC	Up to 24 hours after administration
Cmax	one dosing interval after administration of SOF/VEL (up to 24 hours)

Secondary Outcome Measures

Name	Time	Method
Adverse events	During the entire conduct of the study, maximum of two weeks

Trial Locations

Locations (3)

Jeroen Bosch Hospital; 🇳🇱 's-Hertogenbosch, Netherlands

University of Bonn, Germany; 🇩🇪 Bonn, Germany

Radboud university medical center Department of GI tract; 🇳🇱 Nijmegen, Netherlands