NCT03886701

Doravirine, Rifapentine and Isoniazid Interaction

A Phase 1, Open-Label, Fixed-Sequence, Drug Interaction Study to Investigate the Effect of Once-Weekly Rifapentine and Isoniazid on the Pharmacokinetics of Steady-State Doravirine

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Walter K. Kraft · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

Drug therapy for persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) co-infected with latent tuberculosis infection (LTBI) is complex. Anti-tuberculosis drugs used to treat LTBI often induce drug metabolizing enzymes that share the same metabolic pathway as antiretroviral drugs used for those living with HIV/AIDS. This study evaluates the drug-drug interaction (DDI) potential of an antiretroviral drug when co-administered with a common anti-tuberculosis regimen of drugs.

Detailed description

Rifapentine (RPT) and isoniazid (INH) given once weekly for 12 weeks is commonly used for treating LTBI in adults. For people living with HIV-1, the risks of LTBI is increased. Individuals living with HIV-1 are often on chronic antiretroviral drugs that prevent immunodeficiency and complications associated with infection. Unfortunately, antiretroviral drugs are subject to many DDIs especially with RPT which induces drug clearing enzymes. Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection. Because RPT induces the metabolic pathway in which DOR is removed, there is concern that taking both concomitantly will result in an unwanted DDI leading to reduced DOR concentrations in the blood. Reduced levels will result in loss of efficacy for the drug and therefore not provide adequate viral suppression in those living with HIV. This study investigates the DDI potential of the once weekly regimen RPT and INH together with DOR in healthy volunteers.

Conditions

• Latent Tuberculosis
• Human Immunodeficiency Virus
• Rifamycins Causing Adverse Effects in Therapeutic Use
• Drug Interaction Potentiation

Interventions

Type	Name	Description
DRUG	Doravirine (DOR)	Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
DRUG	Rifapentine (RPT)	Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
DRUG	Isoniazid (INH)	Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

Timeline

• Start date: 2019-04-22
• Primary completion: 2019-05-20
• Completion: 2019-05-20
• First posted: 2019-03-22
• Last updated: 2020-03-27
• Results posted: 2020-03-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study