Dose Escalation Study to Determine the Pharmacokinetics of Atazanavir Administered With RIfampici… (NCT04121195) | Clinical Trial Compass
CompletedPhase 2/3
Dose Escalation Study to Determine the Pharmacokinetics of Atazanavir Administered With RIfampicin to HIV Positive Adults on sEcond-line ART Regimen With Suppressed HIV-1 Viral Load
Uganda26 participantsStarted 2020-10-30
Plain-language summary
The standard treatment for TB consists of rifampicin (RIF) as part of the regimen. However, due to drug-drug interactions (DDI), the bioavailability of PIs is greatly reduced when co-administered with RIF necessitating use of higher doses of the PI to overcome this effect. However, the potential effect of this increased dose on the DDI with bPIs is uncertain. Though some data has been collected that shows safe use of higher doses of LPV to overcome the DDI with standard doses of RIF in HIV-infected individuals, no substantive data has been collected on ATV to correctly adjust its dose when co-administered with RIF-based TB treatment.
Physiologically-based pharmacokinetic (PBPK) modelling was developed to understand ATV and RIF DDIs, and identified potential dosing strategies to overcome this challenge in adults and special populations under workpackage 1 of the VirTUAL consortium. From this work, it is anticipated that the dose of ATV/r should be increased from 300/100 once daily to 300/100mg twice daily in order to overcome the interaction with rifampicin and attain therapeutic plasma concentrations.
This dose escalation trial aims to:
1. Evaluate the steady state plasma and intracellular PK of ATV/r, when administered in adjusted (PBPK model-predicted) doses concurrently with RIF
2. Evaluate the safety and tolerability / acceptability of the adjusted dose of ATV/r that provides the therapeutic concentration when co-administered with RIF.
3. Evaluate the concentration of dolutegravir (DTG) and RIF when co-administered and explore the potential DDI with ATV/r
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Willing and able to provide a signed and dated informed consent
✓. HIV positive male or female ≥ 18 years of age
✓. 50 - 75kg of weight
✓. On ATV/rand 2 nucleos(t)ide reverse transcriptase inhibitor containing ART regimen for at least 6 months
✓. Undetectable HIV viral load (\<50 copies/ml) at screening PLUS an undetectable VL during the most recent test done between 6 and 12 months prior to screening.
✓. A negative pregnancy test for females of child-bearing potential. Should also not be breast feeding.
✓. On or willing to use effective contraception for at least 4 weeks prior to enrolment, throughout the study period and at least 4 weeks after end of the study(please see section 10.3 for a detailed definition of effective contraception for this study).
✓. Clinically stable with no AIDS defining illness within the past 6 months.
Exclusion criteria
✕
What they're measuring
1
Plasma Cmax of ritonavir-boosted Atazanavir
Timeframe: 18 months
2
Plasma AUC of ritonavir-boosted Atazanavir
Timeframe: 18 months
3
Plasma Clearance of ritonavir-boosted Atazanavir
Timeframe: 18 months
4
Intracellular clearance of ritonavir-boosted Atazanavir