Clinical trial NCT02566707: Pharmacokinetics of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2015-10-02
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of atazanavir, dolutegravir and lamivudine
timeFrame: week 2
Secondary outcomes:
measure: efficacy (viral load)
timeFrame: week 2, 6 and 12
measure: number of adverse events
timeFrame: week 2, 6 and 12
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University of Bonn
city: Arnhem
country: Netherlands
facility: Rijstate
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
city: Tilburg
country: Netherlands
facility: St. Elisabeth
Study officials:
References: