Ignite Creation Date:
2025-12-24 @ 12:16 PM
Ignite Modification Date:
2026-01-17 @ 8:26 AM
Study NCT ID:
NCT03892161
Status:
TERMINATED
Last Update Posted:
2019-04-03
First Post:
2018-04-23
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Clinical Evaluation of Adjusted Doses of Darunavir/Ritonavir With Rifampicin in HIV-infected Volunteers
Sponsor:
University of Cape Town
Organization:
Study Overview
Official Title:
Clinical Evaluation of Adjusted Doses of Darunavir/Ritonavir With Rifampicin in HIV-infected Volunteers
Status:
TERMINATED
Status Verified Date:
2019-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Risks to participation
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Darifi
Brief Summary:
The DaRifi study aims:
1. Develop adjusted doses of darunavir/ritonavir for use in HIV-infected patients requiring co-treatment of TB with a rifampicin-based regimen.
2. Compare the steady state pharmacokinetics of doubled doses of DRV/r with rifampicin (in once daily and 12-hourly approaches) to standard daily doses without rifampicin.
3. Twenty-eight volunteers will be enrolled for a target of 24 participants completing the study.
1. Develop adjusted doses of darunavir/ritonavir for use in HIV-infected patients requiring co-treatment of TB with a rifampicin-based regimen.
2. Compare the steady state pharmacokinetics of doubled doses of DRV/r with rifampicin (in once daily and 12-hourly approaches) to standard daily doses without rifampicin.
3. Twenty-eight volunteers will be enrolled for a target of 24 participants completing the study.
Detailed Description:
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: