NCT04424264

The Effect of Rifampicin on the Pharmacokinetics of Intracellular Tenofovir-diphosphate and Tenofovir When Coadministered With Tenofovir Alafenamide Fumarate During the Maintenance Phase of Tuberculosis Treatment in TB/HIV-1 Coinfected Participants

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Professor Francois Venter · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a pharmacokinetic study investigating the effect of rifampicin on the pharmacokinetics of intracellular tenofovir-diphosphate and plasma tenofovir when coadministered with tenofovir alafenamide fumarate during the maintenance phase of tuberculosis treatment in TB/HIV-1 coinfected participants (EpiTAF)

Detailed description

This is an open-label, sequential, single centre pharmacokinetic (PK) study investigating the effect of rifampicin on the pharmacokinetics of intracellular tenofovir-diphosphate and plasma tenofovir when coadministered with tenofovir alafenamide fumarate during the maintenance phase of tuberculosis treatment in TB/HIV-1 coinfected participants (EpiTAF). An open-label, sequential, pharmacokinetic (PK) drug-drug interaction study will be conducted in medically stable virologically suppressed HIV-1 infected adults coinfected with TB, who are in the maintenance phase of their TB treatment. After intensive PK evaluation of IC TFV-DP and pTFV, participants will be switched from their standard-of-care tenofovir disoproxil fumarate (TDF)/FTC/EFV regimen, to TAF + 3TC + EFV at the start of the study treatment period. After 28 days each participant will have intensive PK evaluation of IC TFV-DP and pTFV on TAF + 3TC + EFV with rifampicin (RIF). After the second intensive PK assessment is completed, participants will be switched back to TDF/FTC/EFV, with a final intensive PK evaluation of IC TFV-DP and pTFV 8 days after completion of TB treatment, at the final study visit. Eighteen volunteers will be enrolled for a target of 13 participants completing the study. The study includes screening and enrolment visits, 1 visit on day 28 and an end of study visit 28 days after the end of TB treatment.

Conditions

• HIV-1-infection
• Tuberculosis

Interventions

Type	Name	Description
DRUG	Phase 1: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz coadministered with Rifampicin/Isoniazid	TDF/FTC/EFV 300/200/600 mg once daily plus RIF/INH 600\*/300 mg daily from screening until enrolment (days -15 to 0)
DRUG	Phase 2: Tenofovir alafenamide/Lamivudine/Efavirenz coadministered with Rifampicin/Isoniazid	TAF 25 mg + 3TC 300 mg + EFV 600 mg once daily plus RIF/INH 600/\*300 mg daily (days 1 to ≤ 56)
DRUG	Phase 3: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz	TDF/FTC/EFV 300/200/600 mg once daily. RIF/INH 600mg \<70kg, 750mg \>70kg

Timeline

• Start date: 2019-12-05
• Primary completion: 2020-10-30
• Completion: 2020-10-30
• First posted: 2020-06-09
• Last updated: 2022-06-07

Locations

2 sites across 1 country: South Africa