HCVPhase 4CRUSADE-1NCT03389061
Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
A Phase 4 study testing sofosbuvir/velpatasvir tablet and sofosbuvir/velpatasvir crushed in people with HCV, run by Radboud University Medical Center at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HCV
- What is being tested?
- sofosbuvir/velpatasvir tablet and sofosbuvir/velpatasvir crushed
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Apr 2018to 22 Mar 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Netherlands2 sites
Jeroen Bosch Hospital
's-Hertogenbosch
Radboud university medical center Department of GI tract
Nijmegen
About this study
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.
Read more
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
- Being tested
- sofosbuvir/velpatasvir tablet, sofosbuvir/velpatasvir crushed
- Keywords
- Epclusa, Pharmacokinetics, Crushing
- Medical subject headings
- Pressure Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sofosbuvir/velpatasvir tabletDrug
Single-dose SOF/VEL as a whole tablet in a fasted state.
sofosbuvir/velpatasvir crushedDrug
Single-dose crushed SOF/VEL in a fasted state.
| Study group | Role | What they receive |
|---|---|---|
| sofosbuvir/velpatasvir tablet | Active comparator | Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state. Receives: Drug: sofosbuvir/velpatasvir tablet |
| sofosbuvir/velpatasvir crushed | Experimental | Single-dose crushed sofosbuvir/velpatasvir in a fasted state. Receives: Drug: sofosbuvir/velpatasvir crushed |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC
Measured: Up to 24 hours after administration
Cmax
Measured: one dosing interval after administration of SOF/VEL (up to 24 hours)
Secondary outcomes (1)
Adverse events
Measured: During the entire conduct of the study, maximum of two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2018
- Study start1 Apr 2018
- Primary completion22 Mar 2019
- Study completion22 Mar 2019
Why it stopped: Lack of patients who are eligible for inclusion: less patients on treatment and not using epclusa.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HCVStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Bio-equivalence Study
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03389061
- Sponsor's protocol ID
- UMCN-AKF 16.06
- Acronym
- CRUSADE-1
- Status last verified
- Dec 2020
- First submitted
- 25 Sep 2017
- Last updated
- 7 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32156618
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
- ClinicalTrials.gov ID
- NCT03389061
- Acronym / sponsor ID
- CRUSADE-1 / UMCN-AKF 16.06
- Conditions
- HCV
- Keywords
- Epclusa, Pharmacokinetics, Crushing
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of patients who are eligible for inclusion: less patients on treatment and not using epclusa.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- 22 Mar 2019 (actual)
- Study completion
- 22 Mar 2019 (actual)
- First posted
- 3 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Bio-equivalence Study
| Arm | Type | Receives |
|---|---|---|
| sofosbuvir/velpatasvir tablet | Active comparator | Drug: sofosbuvir/velpatasvir tabletSingle-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state. |
| sofosbuvir/velpatasvir crushed | Experimental | Drug: sofosbuvir/velpatasvir crushedSingle-dose crushed sofosbuvir/velpatasvir in a fasted state. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sofosbuvir/velpatasvir tabletSingle-dose SOF/VEL as a whole tablet in a fasted state. | Drug | sofosbuvir/velpatasvir tablet |
| sofosbuvir/velpatasvir crushedSingle-dose crushed SOF/VEL in a fasted state. | Drug | sofosbuvir/velpatasvir crushed |
Primary outcome
AUC
Time frame: Up to 24 hours after administration
Cmax
Time frame: one dosing interval after administration of SOF/VEL (up to 24 hours)
1 secondary outcome
Adverse events
Time frame: During the entire conduct of the study, maximum of two weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
- Results publication: PubMed 32156618van 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.
- Individual participant dataSharing planned: No
Related trials for HCV
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI
Not yet recruitingObservational study
Elimination of Hepatitis C Virus Among Users of Substances
Hepatitis C in Substance Users
Not yet recruiting
Clinical Study to Evaluate the Performance of the INSTI® HCV Antibody Test for CLIA-Waived Use
HCV Infection
Not yet recruiting
Study to Evaluate the Performance of the INSTI® HCV Antibody Test for Point-of-Care Use in Individuals at Risk for HCV Infection or Presenting With Signs or Symptoms of HCV Infection
HCV Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sofosbuvir/velpatasvir tablet and sofosbuvir/velpatasvir crushed in people with HCV, run by Radboud University Medical Center at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC (time frame: Up to 24 hours after administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03389061, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2020.