Doravirine, Rifapentine and Isoniazid Interaction (DORIIS)
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|ClinicalTrials.gov Identifier: NCT03886701|
Recruitment Status : Completed
First Posted : March 22, 2019
Results First Posted : March 3, 2020
Last Update Posted : March 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Latent Tuberculosis Human Immunodeficiency Virus Rifamycins Causing Adverse Effects in Therapeutic Use Drug Interaction Potentiation||Drug: Doravirine (DOR) Drug: Rifapentine (RPT) Drug: Isoniazid (INH)||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||April 22, 2019|
|Actual Primary Completion Date :||May 20, 2019|
|Actual Study Completion Date :||May 20, 2019|
Period 1: DOR twice-daily alone (Study days 1-4) and Period 2: DOR twice-daily with RPT and INH once-weekly (Study days 7-21)
Drug: Doravirine (DOR)
Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
Other Name: Pifeltro
Drug: Rifapentine (RPT)
Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Other Name: Priftin
Drug: Isoniazid (INH)
Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Other Name: Generic (various)
- Doravirine Maximum Concentration (Cmax) [ Time Frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose ]Doravirine maximum observed concentration during the dosing interval
- Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12) [ Time Frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose ]Doravirine area under the plasma-concentration time curve derived from plasma sampling during one dosing interval
- Doravirine Oral Clearance (CL/F) [ Time Frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose ]Doravirine apparent oral clearance derived from plasma sampling
- Adverse Event [ Time Frame: Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study) ]Safety and tolerability
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03886701
|United States, Pennsylvania|
|Thomas Jefferson University Clinical Research Unit|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Walter K Kraft, MD||Sidney Kimmel Medical College at Thomas Jefferson University|