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CompletedNCT02565888DATE-4Updated Dec 7, 2020

A Drug-drug Interaction Study Between Daclatasvir and Atazanavir/Ritonavir or Atazanavir/Cobicistat

A Phase 1 interventional study of Daclatasvir and Atazanavir in Hepatitis C and HIV, sponsored by Radboud University Medical Center. Completed at 1 site in Netherlands. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-12-07.

Sponsored by Radboud University Medical Center · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
16
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Hepatitis C
  • HIV

Keywords

  • Hepatitis C
  • HIV
  • atazanavir
  • ritonavir
  • daclatasvir
  • cobicistat
03

In context

Hepatitis C

2,321 studies on the registry are indexed under Hepatitis C; 102 are open to participants now.

This study's enrollment of 16 is below the median of 79 across 1,633 interventional studies indexed under Hepatitis C.

Browse Hepatitis C studies →

Lead sponsor

Radboud University Medical Center is the lead sponsor of 959 studies on the registry; 134 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
16 participants (actual)

Study arms

  • 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 · Drug: Atazanavir · Drug: Ritonavir

  • 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 · Drug: Atazanavir · Drug: Cobicistat

Interventions

  • DrugDaclatasvir

    Also known as: Daklinza

  • DrugAtazanavir

    Also known as: Reyataz

  • DrugRitonavir

    Also known as: Norvir

  • DrugCobicistat

    Also known as: Tybost

06

What researchers measure

Primary outcomes

  1. AUC

    Time frame: up to 24 hours after administration

Secondary outcomes

  1. Adverse events

    adverse events will be collected up to 4 weeks in total (entire study)

    Time frame: 4 weeks

07

Study locations

1 site
  • CRCN, Radboud University Medical Center
    Nijmegen, Netherlands
08

References and documents

Publications

  • Smolders EJ, Colbers EP, de Kanter CT, Velthoven-Graafland K, Drenth JP, Burger DM. Daclatasvir 30 mg/day is the correct dose for patients taking atazanavir/cobicistat. J Antimicrob Chemother. 2017 Feb;72(2):486-489. doi: 10.1093/jac/dkw429. Epub 2016 Oct 20. PubMed 27798211 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 7, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02565888
Lead sponsor
Radboud University Medical Center
Responsible party
Sponsor
First posted
Oct 1, 2015
Start date
Nov 2015
Primary completion
Jan 2016
Completion
Jan 2016
Last update
Dec 7, 2020

Study contacts

David Burger, PharmD, PhD
principal investigator · Radboud University Medical Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2020. You cannot join it, but the record below documents what was studied.

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