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Clinical Trials

MainTitle

A Drug-drug Interaction Study Between Daclatasvir and Atazanavir/Ritonavir or Atazanavir/Cobicistat (DATE-4)

This study has been completed
Sponsor
Radboud University


Information provided by (Responsible Party)
Radboud University
ClinicalTrials.gov Identifier
NCT02565888

First received: September 30, 2015
Last updated: January 25, 2016
Last Verified: January 2016
History of Changes
Purpose

Purpose

This study aims to provide the evidence that 150mg of cobicistat will have the same effect on the pharmacokinetics of daclatasvir 30mg QD as 100mg of ritonavir, when given together with atazanavir 300mg.

Condition Intervention Phase
Hepatitis C
HIV

Drug : Daclatasvir
Drug : Atazanavir
Drug : Ritonavir
Drug : Cobicistat
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: A Drug-drug Interaction Study Between the Novel Anti-HCV Agent Daclatasvir and the Antiretroviral Agents Atazanavir/Ritonavir or Atazanavir/Cobicistat in Healthy Volunteers

Further study details as provided by Radboud University:

Primary Outcome Measures

  • AUC [ Time Frame: up to 24 hours after administration ]
Secondary Outcome Measures:
  • Adverse events [ Time Frame: 4 weeks ]
    adverse events will be collected up to 4 weeks in total (entire study)

Enrollment: 16
Study Start Date: November 2015
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: Treatment A
Daclatasvir 30 mg QD film-coated tablet + atazanavir 300mg QD hard capsule + ritonavir 100mg QD from film-coated tablet for 10 days.
Drug: Daclatasvir
Other Name: Daklinza
Drug: Atazanavir
Other Name: Reyataz
Drug: Ritonavir
Other Name: Norvir
Experimental: Treatment B
Daclatasvir 30 mg QD film-coated tablet + atazanavir 300mg QD hard capsule + cobicistat 150mg QD from film-coated tablet for 10 days.
Drug: Daclatasvir
Other Name: Daklinza
Drug: Atazanavir
Other Name: Reyataz
Drug: Cobicistat
Other Name: Tybost

Detailed Description:

Approximately 20-25% of the total number of HIV-infected patients is co-infected with HCV which translates to 6-8 million persons worldwide. Combined treatment of HIV and HCV is complicated by the risk of drug-drug interactions as both the direct acting antiviral agents (DAAs) for HCV as the antiretroviral agents for HIV are substrates of cytochrome P450 (CYP450) or various membrane transporters, and also have the capacity to influence these systems. A careful selection of the appropriate regimens and if needed adjusted doses is key for optimal treatment of both viral infections.
Daclatasvir is a recently approved anti-HCV agent that is a CYP3A4 substrate but does not affect CYP450 itself. It is also a moderate inhibitor of various membrane transporters such as organic anion-transporting polypeptide (OATP1B1), P-glycoprotein (P-gP), and organic cation transporters (OCT2).
Atazanavir/ritonavir is one of the preferred antiretroviral agents in all international guidelines. Ritonavir is used as a boosting agents based on its inhibitory effects on CYP3A. This also inhibits CYP3A-mediated metabolism of daclatasvir and when atazanavir/ritonavir is combined with daclatasvir, it is recommended to reduce the dose of daclatasvir from 60mg QD to 30mg QD.
Cobicistat has recently been approved as an alternative booster of atazanavir at a dose of 150mg QD. It is expected that cobicistat will inhibit CYP3A mediated metabolism of daclatasvir in a similar manner as ritonavir does, but there are no clinical data to support this. As cobicistat lacks some of the adverse events associated with ritonavir use, the use of cobicistat, including as a booster of atazanavir, is likely to increase.
This study aims to provide the evidence that 150mg of cobicistat will have the same effect on the pharmacokinetics of daclatasvir 30mg QD as 100mg of ritonavir, when given together with atazanavir 300mg.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 55 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:

    1. Subject is at least 18 and not older than 55 years at screening.
    2. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to Day 1.
    3. Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
    4. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
    5. Subject is in good age-appropriate health condition as established by medical history, physical examination, and electrocardiography, results of biochemistry, hematology and urinalysis testing within 4 weeks prior to day 1. Results of biochemistry, hematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded.
    6. Subject has a normal blood pressure and pulse rate, according to the Investigator's judgment.


Exclusion Criteria:
    1. Creatinine clearance below 60mL/min.
    2. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
    3. Positive HIV test.
    4. Positive hepatitis B or C test.
    5. Pregnant female (as confirmed by an hCG test performed less than 4 weeks before day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study.
    6. Therapy with any drug (for two weeks preceding Day 1), except for acetaminophen (max 2 gram/day).
    7. Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal and hepatic disorders (clinically relevant increased ALAT/ASAT or hyperbilirubinemia) hormonal disorders (especially diabetes mellitus), coagulation disorders.
    8. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
    9. History of or current abuse of drugs, alcohol or solvents.
    10. Inability to understand the nature and extent of the study and the procedures required.
    11. Participation in a drug study within 60 days prior to Day 1.
    12. Donation of blood within 60 days prior to Day 1.
    13. Febrile illness within 3 days before Day 1.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02565888

Locations

Netherlands
CRCN, Radboud University Medical Center
Nijmegen, Netherlands

Sponsors and Collaborators

Radboud University

Investigators

Principal Investigator: David Burger, PharmD, PhD Radboud University
More Information

More Information


Responsible Party: Radboud University  
ClinicalTrials.gov Identifier: NCT02565888   History of Changes  
Other Study ID Numbers: UMCN-AKF 14.12  
Study First Received: September 30, 2015  
Last Updated: January 25, 2016  

Keywords provided by Radboud University:

Hepatitis C
HIV
atazanavir
ritonavir
daclatasvir
cobicistat

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Ritonavir
Atazanavir Sulfate
Cobicistat
Anti-Retroviral Agents

ClinicalTrials.gov processed this data on October 23, 2017
This information is provided by ClinicalTrials.gov.