Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet (CRUSADE-1)

• ClinicalTrials.gov Identifier: NCT03389061
• Recruitment Status: Withdrawn
• First Posted: January 3, 2018
• Last Update Posted: December 7, 2020
• Sponsor: Radboud University Medical Center
• Information provided by (Responsible Party): Radboud University Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HCV	Drug: sofosbuvir/velpatasvir tablet; Drug: sofosbuvir/velpatasvir crushed	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Bio-equivalence Study
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
• Actual Study Start Date: April 1, 2018
• Actual Primary Completion Date: March 22, 2019
• Actual Study Completion Date: March 22, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: sofosbuvir/velpatasvir tablet; Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state.	Drug: sofosbuvir/velpatasvir tablet; Single-dose SOF/VEL as a whole tablet in a fasted state.
Experimental: sofosbuvir/velpatasvir crushed; Single-dose crushed sofosbuvir/velpatasvir in a fasted state.	Drug: sofosbuvir/velpatasvir crushed; Single-dose crushed SOF/VEL in a fasted state.

Outcome Measures

Primary Outcome Measures :

1. AUC [ Time Frame: Up to 24 hours after administration ]
2. Cmax [ Time Frame: one dosing interval after administration of SOF/VEL (up to 24 hours) ]

Secondary Outcome Measures :

1. Adverse events [ Time Frame: During the entire conduct of the study, maximum of two weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Germany

University of Bonn, Germany

Bonn, Germany

Netherlands

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

Radboud university medical center Department of GI tract

Nijmegen, Netherlands

Sponsors and Collaborators

Radboud University Medical Center

More Information

Publications of Results:

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.

• Responsible Party: Radboud University Medical Center
• ClinicalTrials.gov Identifier: NCT03389061
• Other Study ID Numbers: UMCN-AKF 16.06
• First Posted: January 3, 2018
• Last Update Posted: December 7, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Radboud University Medical Center:

Epclusa; Pharmacokinetics; Crushing

Additional relevant MeSH terms:

Crush Injuries; Wounds and Injuries; Sofosbuvir; Velpatasvir; Sofosbuvir-velpatasvir drug combination; Antiviral Agents; Anti-Infective Agents