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

Sponsor
Radboud University Medical Center (Other)
Overall Status
Withdrawn
CT.gov ID
NCT03389061
Collaborator
(none)
0
3
2
11.7
0
0

Study Details

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
  • Drug: sofosbuvir/velpatasvir tablet
  • Drug: sofosbuvir/velpatasvir crushed
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Bio-equivalence StudyBio-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 :
Apr 1, 2018
Actual Primary Completion Date :
Mar 22, 2019
Actual Study Completion Date :
Mar 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 [Up to 24 hours after administration]

  2. Cmax [one dosing interval after administration of SOF/VEL (up to 24 hours)]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Site City State Country Postal Code
1 University of Bonn, Germany Bonn Germany
2 Jeroen Bosch Hospital 's-Hertogenbosch Netherlands
3 Radboud university medical center Department of GI tract Nijmegen Netherlands

Sponsors and Collaborators

  • Radboud University Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Radboud University Medical Center
ClinicalTrials.gov Identifier:
NCT03389061
Other Study ID Numbers:
  • UMCN-AKF 16.06
First Posted:
Jan 3, 2018
Last Update Posted:
Dec 7, 2020
Last Verified:
Dec 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 7, 2020