Pharmacokinetics of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen

NCT02566707 — Phase 2, Terminated, 9 participants, Radboud University Medical Center

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Pharmacokinetics, Safety and Efficacy of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen in Patients With Intolerance and/or Resistance to NRTIs, NNRTIs and RTV: A Pilot Study

Registry	NCT02566707, acronym PRADAII
Status	Terminated - due to introduction of another integrase inhibitor, recruitement was not feasible anymore.
Phase	Phase 2
Study type	Interventional; na, single group, masking: none, treatment
Enrollment	9 (Actual)
Sponsor	Radboud University Medical Center (Other)
Conditions	HIV-1 Infection
Interventions	Atazanavir, Dolutegravir, Lamivudine (Drug)
Dates	start 2015-08-01, primary completion 2016-12-01, completion 2016-12-01, first posted 2015-10-02, last updated 2020-12-07
Locations	4 sites in Germany, Netherlands

-Summary

During the past years the treatment of HIV-1 infection has transformed towards chronic treatment. Patients are being treated with antiretroviral drugs for many years and become older. The risk of developing side-effects due to long term antiretroviral therapy is therefore more and more likely. New alternative once-daily maintenance regimes are needed for those who are extensively pre-treated and experience side-effects or toxicity on standard treatment combinations. A possible once-daily, fully active maintenance regimen is the combination of atazanavir (unboosted), dolutegravir and lamivudine (PRADAII regimen). This combination is expected to be a safe, once-daily maintenance regimen with a favorable side-effect profile. The combination suits patients with intolerance and/or resistance to NRTIs, NNRTIs and ritonavir, who have a suppressed viral load. However, for this new combination the pharmacokinetic profile is unknown and there are no data on short-term and long-term safety and efficacy. This study wille therefore asses the pharmacokinetics, safety and efficacy in a small number of HIV-1 infected patients.

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+Arms and interventions

Arm	Type	Interventions	Description
PRADAII regimen	Experimental	Drug: Atazanavir; Drug: Dolutegravir; Drug: Lamivudine	Use of PRADAII regimen during 12 weeks. This regimen consists of atazanavir 400 mg QD, dolutegravir 50 mg QD, lamivudine 300 mg QD.

Atazanavir (Drug), also known as Reyataz: HIV therapy will be adapted: atazanavir 400mg QD
Dolutegravir (Drug), also known as Tivicay: HIV therapy will be adapted: dolutegravir 50mg QD
Lamivudine (Drug), also known as Epivir: HIV therapy will be adapted: lamivudine 300mg QD

+Outcome measures

Primary outcomes

Area under the plasma concentration versus time curve (AUC) of atazanavir, dolutegravir and lamivudine [week 2]: Pharmacokinetic parameters of atazanavir, dolutegravir and lamivudine

Secondary outcomes

efficacy (viral load) [week 2, 6 and 12]: efficacy (viral load) of the combination of atazanavir, dolutegravir and lamivudine
number of adverse events [week 2, 6 and 12]: number of adverse events of the combination of atazanavir, dolutegravir and lamivudine

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
* Subject is in need for a switch in maintenance regimen due to adverse effects, toxicities, simplification and/or resistance.
* Subject is at least 18 years of age at the day of screening.
* Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
* HIV-1 RNA < 40 copies/mL for at least 6 months on antiretroviral therapy prior to inclusion.
* Subject has no documented resistance mutations to PIs, INSTIs or lamivudine.

Exclusion Criteria:

* Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
* Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
* Inability to understand the nature and extent of the trial and the procedures required.
* Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
* Abnormal serum transaminases determined as levels being > 5 times upper limit of normal.
* Renal failure determined as an estimated Glomerular Filtration Rate (eGFR) < 50 ml/min (MDRD-based).
* Concomitant use of medications that interfere with atazanavir, dolutegravir or lamivudine pharmacokinetics: oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John's wort, rifampicin, clarithromycin, H2 receptor antagonists, proton pump inhibitors, irinotecan, midazolam, triazolam, buprenorphine, aprepitant, modafinil, imatinib, co-trimoxazole, other antiretroviral drugs.
* Concomitant use of medications that are contraindicated for use with atazanavir, dolutegravir or lamivudine: alfuzosin, dofetilide, pimozide, quetiapine, quinidine, bepridil, simvastatin, atorvastatin, lovastatin, sildenafil (as for use in pulmonary arterial hypertension), cladribine.
* Active hepatobiliary or hepatic disease (including chronic hepatitis B or C infection).
* Alcohol abuse.

+Locations (4)

Facility	City	Country
University of Bonn	Bonn	Germany
Rijstate	Arnhem	Netherlands
Radboud University Nijmegen Medical Centre	Nijmegen	Netherlands
St. Elisabeth	Tilburg	Netherlands