Pharmacokinetics of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen

HIV-1 Infection Clinical Trial

— PRADAII  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02566707
• Other study ID #: UMCN-AKF 14.08
• Status: Terminated
• Phase: Phase 2
• Start date: August 2015
• Est. completion date: December 2016

Study information

• Verified date: December 2020
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Atazanavir
HIV therapy will be adapted: atazanavir 400mg QD
• Dolutegravir
HIV therapy will be adapted: dolutegravir 50mg QD
• Lamivudine
HIV therapy will be adapted: lamivudine 300mg QD

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Countries where clinical trial is conducted

Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration versus time curve (AUC) of atazanavir, dolutegravir and lamivudine	Pharmacokinetic parameters of atazanavir, dolutegravir and lamivudine	week 2
Secondary	efficacy (viral load)	efficacy (viral load) of the combination of atazanavir, dolutegravir and lamivudine	week 2, 6 and 12
Secondary	number of adverse events	number of adverse events of the combination of atazanavir, dolutegravir and lamivudine	week 2, 6 and 12

External Links

•   Abstract page 36