PRADAII: Pharmacokinetics of Atazanavir /Dolutegravir/Lamivudine Regimen as Maintenance Regimen

Sponsor

Radboud University Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT02566707

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

2.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: Atazanavir Drug: Dolutegravir Drug: Lamivudine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Dec 1, 2016

Actual Study Completion Date :

Dec 1, 2016

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	University of Bonn	Bonn	Germany
2	Rijstate	Arnhem	Netherlands
3	Radboud University Nijmegen Medical Centre	Nijmegen	Netherlands
4	St. Elisabeth	Tilburg	Netherlands

Sponsors and Collaborators

Radboud University Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Abstract page 36

Publications

None provided.

Responsible Party:

Radboud University Medical Center

ClinicalTrials.gov Identifier:

NCT02566707

Other Study ID Numbers:

UMCN-AKF 14.08

First Posted:

Oct 2, 2015

Last Update Posted:

Dec 7, 2020

Last Verified:

Dec 1, 2020

Additional relevant MeSH terms:

Lamivudine

Atazanavir Sulfate

Dolutegravir

Study Results

No Results Posted as of Dec 7, 2020