A Phase 1 interventional study of Darunavir/ritonavir 800/100 mg tablet and Rifampicin 600mg QD tablet and DTG 50mg BD in HIV Infections, sponsored by University of Cape Town. Terminated at 1 site in South Africa. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2019-04-03.
Sponsored by University of Cape Town · Phase 1, Interventional, and Treatment
The DaRifi study aims:
A significant barrier to the use of better tolerated antiretrovirals in many low-to-middle income countries (LMIC), where tuberculosis (TB) is endemic, is a lack of evidence to support their use in patients with TB. Access to optimal protease inhibitor (PI)-based regimens for patients with and without TB is urgent. Switching rifampicin to rifabutin, a weak inducer that does not significantly reduce PI concentrations, is recommended in high income countries for patients on boosted PIs who develop TB. However, rifabutin is not available in most LMIC where TB is typically treated with fixed dose combination tablets.
We will enrol virologically suppressed participants on a second-line DRV/r regimen without TB. Based on data from a Physiologically-Based PK model, we selected two adjusted doses of DRV/r (1600/200 mg daily and 800/100 mg 12 hourly) with RIF for comparison to plasma exposures with DRV/r 800/100 mg daily without RIF, in a cross-over design.
Baseline DRV steady state PK will be determined and RIF added for 7 days, then the dose of ritonavir will be increased to 200 mg; 7 days later the dose of DRV will be increased; after another 7 days participants will be crossed over to the alternative adjusted DRV dose.
DRV will be measured in plasma samples after observed doses at baseline and after each dose adjustment. Non-compartmental analysis will be used to estimate the PK measures. Clinical adverse events, ALT, and bilirubin will be monitored every 2 to 3 days during treatment with RIF.
4,340 studies on the registry are indexed under HIV Infections; 240 are open to participants now.
This study's enrollment of 17 is below the median of 83 across 3,312 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →University of Cape Town is the lead sponsor of 116 studies on the registry; 14 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria
Exclusion criteria (volunteers meeting any of the criteria will be excluded)
Standard dose DRV/r 800/100mg without Rifampicin
Drug: Darunavir/ritonavir 800/100 mg tablet
Rifampicin 600mg QD will be added and darunavir/ritonavir steady state pharmacokinetic analysis will be performed.
Drug: Darunavir/ritonavir 800/100 mg tablet · Drug: Rifampicin 600mg QD tablet and DTG 50mg BD
Rifampicin 600mg QD continued with ritonavir 200mg dose doubled QD and darunavir remains 800mg QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared.
Drug: Darunavir/ritonavir 800/100 mg tablet · Drug: Rifampicin 600mg QD tablet and DTG 50mg BD
Rifampicin 600mg QD and DTG QD continued. Double dose DRV/r QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared.
Drug: Darunavir/ritonavir 800/100 mg tablet · Drug: Rifampicin 600mg QD tablet and DTG 50mg BD
Rifampicin 600mg QD and DTG BD continued. Double dose DRV/r QD. The darunavir/ritonavir steady state pharmacokinetic analysis will be performed and compared.
Drug: Darunavir/ritonavir 800/100 mg tablet · Drug: Rifampicin 600mg QD tablet and DTG 50mg BD
Standard dose DRV/r administered
Drug page: Rifampin
Rifampicin and DTG added
Darunavir plasma concentrations nanogram per milliliter (ng/ml)
Darunavir plasma concentrations will be compared with rifampicin and without rifampicin.
Time frame: 1 year
Alanine Transaminase (ALT) blood level (iu/L)
Clinical safety will be monitored, ALT liver enzyme tests will be evaluated every 3 days.
Time frame: 1 Year
Plan to share: No
Ran from Apr 2018 to primary completion in Nov 2018, 7 months.
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This study is terminated, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.
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