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

NCT03389061 | Withdrawn Phase 4

• 1 other identifier: UMCN-AKF 16.06
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 3

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.

Conditions

HCV

Keywords

Epclusa; Pharmacokinetics; Crushing

Outcome Measures

Primary Outcomes (2)

• AUC

  Up to 24 hours after administration

• Cmax

  one dosing interval after administration of SOF/VEL (up to 24 hours)

Secondary Outcomes (1)

• Adverse events

  During the entire conduct of the study, maximum of two weeks

Study Arms (2)

sofosbuvir/velpatasvir tablet

ACTIVE COMPARATOR

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

Drug: sofosbuvir/velpatasvir tablet

sofosbuvir/velpatasvir crushed

EXPERIMENTAL

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

Drug: sofosbuvir/velpatasvir crushed

Interventions

sofosbuvir/velpatasvir tablet DRUG

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

sofosbuvir/velpatasvir tablet

sofosbuvir/velpatasvir crushed DRUG

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

sofosbuvir/velpatasvir crushed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (3)

University of Bonn, Germany

Bonn, Germany

Location

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

Location

Radboud university medical center Department of GI tract

Nijmegen, Netherlands

Location

Related 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. Epub 2020 Mar 7. No abstract available.

  PMID: 32156618 RESULT

MeSH Terms

Conditions

Pressure Ulcer

Interventions

sofosbuvir-velpatasvir drug combination; Sofosbuvir

Condition Hierarchy (Ancestors)

Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Bio-equivalence Study

Study Record Dates

• First Submitted: September 25, 2017
• First Posted: January 3, 2018
• Study Start: April 1, 2018
• Primary Completion: March 22, 2019
• Study Completion: March 22, 2019
• Last Updated: December 7, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); NL (2)