Pharmacokinetics of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen

NCT02566707 | Terminated Phase 2

• 1 other identifier: UMCN-AKF 14.08
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 4

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Area under the plasma concentration versus time curve (AUC) of atazanavir, dolutegravir and lamivudine

  Pharmacokinetic parameters of atazanavir, dolutegravir and lamivudine

  week 2

Secondary Outcomes (2)

• efficacy (viral load)

  week 2, 6 and 12

• number of adverse events

  week 2, 6 and 12

Study Arms (1)

PRADAII regimen

EXPERIMENTAL

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; Drug: Dolutegravir; Drug: Lamivudine

Interventions

Atazanavir DRUG

HIV therapy will be adapted: atazanavir 400mg QD

Also known as: Reyataz

PRADAII regimen

Dolutegravir DRUG

HIV therapy will be adapted: dolutegravir 50mg QD

Also known as: Tivicay

PRADAII regimen

Lamivudine DRUG

HIV therapy will be adapted: lamivudine 300mg QD

Also known as: Epivir

PRADAII regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subject has no documented resistance mutations to PIs, INSTIs or lamivudine.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (4)

University of Bonn

Bonn, Germany

Location

Rijstate

Arnhem, Netherlands

Location

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

Location

St. Elisabeth

Tilburg, Netherlands

Location

Related Links

• Abstract page 36

MeSH Terms

Interventions

Atazanavir Sulfate; dolutegravir; Lamivudine

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2015
• First Posted: October 2, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: December 7, 2020

Record last verified: 2020-12

Locations

DE (1); NL (3)