Pharmacokinetics of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen (PRADAII)

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

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.

Study Overview

• Status: Terminated
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Atazanavir; Drug: Dolutegravir; Drug: Lamivudine

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany
    • University of Bonn
• Netherlands
  • Arnhem, Netherlands
    • Rijstate
  • Nijmegen, Netherlands
    • Radboud University Nijmegen Medical Centre
  • Tilburg, Netherlands
    • St. Elisabeth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRADAII regimen; Use of PRADAII regimen during 12 weeks. This regimen consists of atazanavir 400 mg QD, dolutegravir 50 mg QD, lamivudine 300 mg QD.	Drug: Atazanavir; HIV therapy will be adapted: atazanavir 400mg QD; Other Names: Reyataz; Drug: Dolutegravir; HIV therapy will be adapted: dolutegravir 50mg QD; Other Names: Tivicay; Drug: Lamivudine; HIV therapy will be adapted: lamivudine 300mg QD; Other Names: Epivir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC) of atazanavir, dolutegravir and lamivudine	Pharmacokinetic parameters of atazanavir, dolutegravir and lamivudine	week 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy (viral load)	efficacy (viral load) of the combination of atazanavir, dolutegravir and lamivudine	week 2, 6 and 12
number of adverse events	number of adverse events of the combination of atazanavir, dolutegravir and lamivudine	week 2, 6 and 12

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Publications and helpful links

Helpful Links

• Abstract page 36

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: September 2, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): December 7, 2020
• Last Update Submitted That Met QC Criteria: December 4, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Lamivudine; Atazanavir Sulfate; Dolutegravir
• Other Study ID Numbers: UMCN-AKF 14.08