Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet (CRUSADE-1)
Primary Purpose
HCV
Status
Withdrawn
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
sofosbuvir/velpatasvir tablet
sofosbuvir/velpatasvir crushed
Sponsored by
About this trial
This is an interventional other trial for HCV focused on measuring Epclusa, Pharmacokinetics, Crushing
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- University of Bonn, Germany
- Jeroen Bosch Hospital
- Radboud university medical center Department of GI tract
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
sofosbuvir/velpatasvir tablet
sofosbuvir/velpatasvir crushed
Arm Description
Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state.
Single-dose crushed sofosbuvir/velpatasvir in a fasted state.
Outcomes
Primary Outcome Measures
AUC
Cmax
Secondary Outcome Measures
Adverse events
Full Information
NCT ID
NCT03389061
First Posted
September 25, 2017
Last Updated
December 4, 2020
Sponsor
Radboud University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03389061
Brief Title
Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
Acronym
CRUSADE-1
Official Title
Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of patients who are eligible for inclusion: less patients on treatment and not using epclusa.
Study Start Date
April 1, 2018 (Actual)
Primary Completion Date
March 22, 2019 (Actual)
Study Completion Date
March 22, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HCV
Keywords
Epclusa, Pharmacokinetics, Crushing
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Bio-equivalence Study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
sofosbuvir/velpatasvir tablet
Arm Type
Active Comparator
Arm Description
Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state.
Arm Title
sofosbuvir/velpatasvir crushed
Arm Type
Experimental
Arm Description
Single-dose crushed sofosbuvir/velpatasvir in a fasted state.
Intervention Type
Drug
Intervention Name(s)
sofosbuvir/velpatasvir tablet
Intervention Description
Single-dose SOF/VEL as a whole tablet in a fasted state.
Intervention Type
Drug
Intervention Name(s)
sofosbuvir/velpatasvir crushed
Intervention Description
Single-dose crushed SOF/VEL in a fasted state.
Primary Outcome Measure Information:
Title
AUC
Time Frame
Up to 24 hours after administration
Title
Cmax
Time Frame
one dosing interval after administration of SOF/VEL (up to 24 hours)
Secondary Outcome Measure Information:
Title
Adverse events
Time Frame
During the entire conduct of the study, maximum of two weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Facility Information:
Facility Name
University of Bonn, Germany
City
Bonn
Country
Germany
Facility Name
Jeroen Bosch Hospital
City
's-Hertogenbosch
Country
Netherlands
Facility Name
Radboud university medical center Department of GI tract
City
Nijmegen
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32156618
Citation
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.
Results Reference
result
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Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
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