NCT04272242

Drug-Drug Interactions Between Rifapentine and Dolutegravir in HIV/LTBI Co-Infected Individuals

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This study evaluated the potential drug-drug interactions between dolutegravir (DTG) and steady state rifapentine (RPT) when RPT was given with isoniazid (INH) daily for 4 weeks (1HP) as part of treatment for latent TB infection (LTBI) in HIV-1 and LTBI co-infected individuals.

Detailed description

The purpose of this study was to evaluate the potential drug-drug interactions between dolutegravir (DTG) and steady state rifapentine (RPT) when RPT was given with isoniazid (INH) daily for 4 weeks (1HP) as part of treatment for latent TB infection (LTBI) in HIV-1 and LTBI co-infected individuals. Participants received study-provided INH and RPT once daily for 4 weeks (1HP). During the 1HP treatment, DTG was administered twice daily in Arm 1. Arm 2 planned to administer DTG once daily. At study entry, all participants were required to be on DTG-based antiretroviral (ARV) treatment with 2 nucleoside reverse transcriptase inhibitors (NRTIs) (tenofovir alafenamide \[TAF\] was prohibited) during the study. In Arm 1, DTG 50 mg was administered twice daily; the morning dose from non-study ARV supply and the evening dose from study supply. Participants were also required to receive pyridoxine (vitamin B6) with each dose of INH based on the current local, national, or international dosing guidelines. NRTI therapy and pyridoxine (vitamin B6) was not provided by the study. The majority of Arm 1 participants were on study for 6 weeks (a 4-week on-study treatment period and a 2-week follow-up period). Arm 1 participants could be on study for up to 11 weeks if the on-study treatment duration was extended or if participants needed additional follow-up visits to measure viral load. The study began enrollment with Arm 1. Opening of Arm 2 was dependent upon assessment of DTG pharmacokinetics (PK) data from participants in Arm 1. Arm 1 is complete and results are reported. Arm 2 was not conducted based on the Arm 1 PK assessment.

Conditions

• HIV Infection
• LTBI

Interventions

Type	Name	Description
DRUG	Dolutegravir (DTG)	Administered orally
DRUG	Isoniazid (INH)	Administered orally
DRUG	Rifapentine (RPT)	Administered orally
DRUG	Antiretroviral Therapy (ART)	Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
DIETARY_SUPPLEMENT	Pyridoxine (Vitamin B6)	Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.

Timeline

• Start date: 2021-02-27
• Primary completion: 2021-12-15
• Completion: 2021-12-27
• First posted: 2020-02-17
• Last updated: 2024-09-19
• Results posted: 2024-08-09

Locations

10 sites across 7 countries: United States, Botswana, Haiti, Malawi, South Africa, Thailand, Zimbabwe

Regulatory

• FDA-regulated drug study