Impact of Once-Weekly Rifapentine and Isoniazid on the Steady State Pharmacokinetics of Dolutegravir and Darunavir Boosted With Cobicistat in Healthy Volunteers
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|ClinicalTrials.gov Identifier: NCT02771249|
Recruitment Status : Completed
First Posted : May 13, 2016
Last Update Posted : December 30, 2021
People with human immunodeficiency virus (HIV) often take several medicines to control HIV. Dolutegravir and darunavir boosted with cobicistat are HIV medicines that people may take. They may also need to take medicines for an infection called latent tuberculosis (TB). Researchers think a once-weekly treatment for latent TB would be easier for people with HIV to take. This once weekly treatment consists of two drugs: rifapentine and isoniazid. However, they need to see how TB drugs and HIV drugs interact.
To learn how anti-HIV and anti-TB drugs affect each other so that people taking these drugs together can be treated safely.
Healthy adults ages 18 65.
Participants will be screened with a medical history and physical exam. They will have vital signs taken and give a blood sample. Women will have a pregnancy test.
Participants cannot take any other medicines during the study, including vitamins. Only occasional, infrequent use of acetaminophen (Tylenol , max 2000 mg/day), ibuprofen (Motrin or Advil ), naproxen (Aleve ), loperamide (Imodium ), and/or antihistamines (such as Benadryl , Zyrtec , Claritin , etc.) will be allowed.
Participants will be assigned to one of three groups. Each group will take a different study drug, once or twice a day, for 19 23 days. At the baseline study visit, they will get a supply of the study drug tablets and instructions for taking them. Participants will keep a medicine diary to serve as a memory aid for taking medicine and reporting any side effects that they may experience.
Participants will have 8 or 9 study visits over about 40 days. The number of visits depends on which group the person is assigned to. All visits will take place at the NIH Clinical Center. Participants will fast before study visits.
The baseline visit will last about 2 3 hours. There will be 3-4 long visits that will last for about 12 hours. The other 4-5 visits will last about 1 hour.
During all study visits, screening procedures will be repeated. During long visits, an intravenous (IV) line will be inserted into an arm vein with a needle. It will be used to take blood.
|Condition or disease||Intervention/treatment||Phase|
|HIV Infected Population With Latent Tuberculosis||Drug: rifapentene (RPT) Drug: darunavir/cobicistat (DRV/c) Drug: Isoniazid (INH) Dietary Supplement: Pyridoxine||Phase 1|
Rifapentine (RPT) is a long-acting rifamycin that can be used weekly with isoniazid (INH) as a first-line regimen in the treatment of latent tuberculosis infection (LTBI). Although this regimen offers several potential benefits, the use of weekly RPT plus INH is not currently recommended in adults infected with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) due to limited evidence on drug interactions with antiretrovirals (ARVs).1Darunavir boosted with cobicistat (DRV/c) comprises part of alternative treatment regimens recommended for the treatment of HIV.2However, drug interactions between these ARV agents and RPT are of concern. Thus, the purpose of this study is to determine the effects of concomitant RPT and INH administration on the steady state PK of DRV/c.
This is an open-label, fixed sequence, intrasubject drug-drug interaction study designed to evaluate the steady state PK of DRV/c with coadministration of once weekly RPT and INH given at doses used to treat LTBI. Arm B will be comprised of two phases: (1) DRV/c once daily alone (days 1-4) and (2) DRV/c once daily + (RPT and INH) once weekly (days 5-19). Participants in Arm B will undergo periodic serial ARV PK blood draws on days 4, 14, and 19.
DRV/c PK parameters will be determined using non-compartmental methods. Cobicistat levels will only be assessed if DRV concentrations are significantly decreased. The following PK parameters will be compared between phases: area under the curve over the dosing interval, maximum plasma concentration, time to maximum plasma concentration, terminal half-life, apparent oral clearance, and minimum plasma concentration. Adverse events will be graded and recorded.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Impact of Once-Weekly Rifapentine and Isoniazid on the Steady State Pharmacokinetics of Dolutegravir and Darunavir Boosted With Cobicistat in Healthy Volunteers|
|Actual Study Start Date :||June 3, 2016|
|Actual Primary Completion Date :||August 17, 2021|
|Actual Study Completion Date :||August 17, 2021|
Experimental: Arm B
Arm B will be comprised of two phases: (1) DRV/c once daily alone (days 1-4) and (2) DRV/c once daily + RPT and INH once weekly (days 5-19).
Drug: rifapentene (RPT)
RPT is a long-acting rifamycin used in combination with INH in the treatment of LTBI.
Drug: darunavir/cobicistat (DRV/c)
DRV is a protease inhibitor (PI) indicated in the treatment of HIV infection.33 DRV requires coadministration with RTV (100 mg once or twice daily) or COBI (150 mg daily), the latter of which has been coformulated into a fixed-dose tablet with DRV (DRV/c 800/150 mg).
Drug: Isoniazid (INH)
INH is an antimycobacterial agent that can be used alone or in combination with RPT for the treatment of LTBI. Given with Pyridoxine (vitamin B6)
Dietary Supplement: Pyridoxine
- Area-under-the-curve during the dosing interval of 0 to t (AUC0-t), maximum total plasma concentration (Cmax), time to maximum plasma concentration (t-max), terminal halflife (t1/2), apparent oral clearance (CL/F) [ Time Frame: Days 4 14, and 19 ]To assess the effects of once weekly administration of RPT and INH given at doses used for treating LTBI on the steady state PK of DRV/c
- AEs and abnormal laboratory values graded according to the Division of AIDS AE Table, laboratory measures: hepatic & renal function, lipids, complete blood count, creatine kinase & lipase [ Time Frame: Day 34 ]To assess the safety of coadministration of DRV/c with once weekly RPT and INH through documentation of adverse events (AE) according to the Division of AIDS AE table
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): NCT02771249
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Joseph A Kovacs, M.D.||National Institutes of Health Clinical Center (CC)|