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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03389061
Recruitment Status : Not yet recruiting
First Posted : January 3, 2018
Last Update Posted : January 3, 2018
Sponsor:
Information provided by (Responsible Party):

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)
Estimated Enrollment : 14 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
Anticipated Study Start Date : February 1, 2018
Estimated Primary Completion Date : December 1, 2018
Estimated Study Completion Date : December 1, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir
U.S. FDA Resources

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03389061


Contacts
Contact: Minou van Seyen, MSc +31 24 361 64 05 minou.vanseyen@radboudumc.nl
Contact: David M Burger, Prof. +31 24 361 64 05 David.Burger@radboudumc.nl

Locations
Germany
University of Bonn, Germany Not yet recruiting
Bonn, Germany
Contact: Juergen Rockstroh         
Netherlands
Jeroen Bosch Hospital Not yet recruiting
's-Hertogenbosch, Netherlands
Contact: Bram Schaap         
Sub-Investigator: Jeroen Derijks         
Radboud university medical center Department of GI tract Not yet recruiting
Nijmegen, Netherlands
Contact: Joost Drenth         
Sponsors and Collaborators
Radboud University
More Information

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03389061     History of Changes
Other Study ID Numbers: UMCN-AKF 16.06
First Posted: January 3, 2018    Key Record Dates
Last Update Posted: January 3, 2018
Last Verified: January 2018
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:
Epclusa
Pharmacokinetics
Crushing

Additional relevant MeSH terms:
Sofosbuvir
Antiviral Agents
Anti-Infective Agents