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

NCT ID: NCT03389061

Last Updated: 2020-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE4

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-01

Study Completion Date

2019-03-22

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.

Detailed Description

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Conditions

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HCV

Keywords

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Epclusa Pharmacokinetics Crushing

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Bio-equivalence Study
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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sofosbuvir/velpatasvir tablet

Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state.

Group Type ACTIVE_COMPARATOR

sofosbuvir/velpatasvir tablet

Intervention Type DRUG

Single-dose SOF/VEL as a whole tablet in a fasted state.

sofosbuvir/velpatasvir crushed

Single-dose crushed sofosbuvir/velpatasvir in a fasted state.

Group Type EXPERIMENTAL

sofosbuvir/velpatasvir crushed

Intervention Type DRUG

Single-dose crushed SOF/VEL in a fasted state.

Interventions

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sofosbuvir/velpatasvir tablet

Single-dose SOF/VEL as a whole tablet in a fasted state.

Intervention Type DRUG

sofosbuvir/velpatasvir crushed

Single-dose crushed SOF/VEL in a fasted state.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Bonn, Germany

Bonn, , Germany

Site Status

Jeroen Bosch Hospital

's-Hertogenbosch, , Netherlands

Site Status

Radboud university medical center Department of GI tract

Nijmegen, , Netherlands

Site Status

Countries

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Germany Netherlands

References

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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.

Reference Type RESULT
PMID: 32156618 (View on PubMed)

Other Identifiers

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UMCN-AKF 16.06

Identifier Type: -

Identifier Source: org_study_id