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

  • STATUS
    Recruiting
  • End date
    May 31, 2022
  • participants needed
    72
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 30 August 2021
ct scan
platelet count
body mass index
total bilirubin
hysterectomy
absolute neutrophil count
antiretroviral
antiretroviral agents
antiretroviral therapy
hiv test
dolutegravir
western blot
interferon
isoniazid
chest radiograph
urine test
HIV Vaccine
investigational new drug
skin test
tuberculin test
immune globulin
antibody test
interferon-gamma release assay
hiv-1 infection
rifapentine
hiv-1 rna measurement
hiv-1 antigen

Summary

This study will evaluate the potential drug-drug interactions between dolutegravir (DTG) and steady state rifapentine (RPT) when RPT is 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.

Description

The purpose of this study is to evaluate the potential drug-drug interactions between dolutegravir (DTG) and steady state rifapentine (RPT) when RPT is 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 will receive study-provided INH and RPT once daily for 4 weeks (1HP). During the 1HP treatment, DTG will be administered twice daily in Arm 1, and once daily in Arm 2.

At study entry, all participants must also be on DTG-based antiretroviral (ARV) treatment with 2 nucleoside reverse transcriptase inhibitors (NRTIs) (excluding tenofovir alafenamide [TAF]) during the study. In Arm 1 participants, DTG 50 mg will be administered twice daily; the morning dose from non-study ARV supply and the evening dose from study supply. In Arm 2 participants, DTG 50 mg will be administered once daily, in the morning, from non-study ARV supply.

Participants must 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) will not be provided by the study.

The study will begin enrollment with Arm 1. Opening of Arm 2 will depend on assessment of DTG pharmacokinetics (PK) data from participants in Arm 1.

The majority of participants will be on study for 6 weeks (a 4-week on-study treatment period and a 2-week follow-up period). Some participants may be on study for up to 11 weeks if the on-study treatment duration has been extended or if participants need to have additional follow-up visits to measure viral load.

Details
Condition Latent Tuberculosis, HIV infection, Immunodeficiency, Primary Immunodeficiency Disorders, HIV Infections, LTBI, human immunodeficiency virus, hiv disease, latent tb
Treatment Dolutegravir (DTG), Isoniazid (INH), Rifapentine (RPT), Pyridoxine (vitamin B6), Antiretroviral Therapy (ART)
Clinical Study IdentifierNCT04272242
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on30 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Males and females at least 18 but no more than 65 years of age at study entry
Ability and willingness of participant or legal guardian/representative to provide informed consent
Weight 40 kg and a body mass index (BMI) of greater than 18.5 kg/m^2
Documentation of HIV-1 infection status, as below
HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000 copies/mL are also acceptable as documentation of HIV-1 infection
Note A: The term "licensed" refers to a US Food and Drug Administration (FDA)-approved kit, which is required for all investigational new drug (IND) studies, or for sites that are located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies
Note B: World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load
HIV-1 plasma viral load <50 copies/mL obtained within 30 days prior to study entry by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that is Virology Quality Assessment (VQA) certified
At US sites: Evidence of LTBI by tuberculin skin test (TST) reactivity 5 mm, or a positive interferon gamma release assay (IGRA) at any time prior to study entry
At non-US sites: Indication for LTBI treatment according to WHO latent TB guidelines (Note: TST/IGRA results not required)
On a stable once daily DTG (50 mg) based ART with once daily 2 NRTIs and
with at least 28 total days of DTG and NRTI dosing prior to study entry
with no gaps in self-reported DTG and NRTI adherence of more than 3 consecutive days in the 28 days prior to study entry
with no intention to change ART for the duration of the study
NOTE A: Participants who switch from another ART regimen to DTG to meet eligibility requirements for this study will be eligible to enroll as long as the ART is switched at least 28 days prior to study entry
Chest radiograph or chest computed tomography (CT) scan performed within 30 days prior to study entry without evidence of active TB
The following laboratory values obtained within 30 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practice (GCLP) and participates in appropriate external quality assurance programs
Absolute neutrophil count (ANC) >750 cells/mm^3
Hemoglobin 7.4 g/dL
Platelet count 50,000/mm^3
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) <2.5 X the upper limit of normal (ULN)
Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) <2.5 X ULN
Total bilirubin 1.5 x ULN
Creatinine <1.3 ULN
For females of reproductive potential, negative serum or urine pregnancy test at Screening within 30 days prior to entry and within 48 hours prior to entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs
NOTE A: If screening visit occurs within 48 hours prior to entry, only one test will occur prior to entry
NOTE B: Urine test must have a sensitivity of 15-25 mIU/mL
Female participants of reproductive potential must agree not to participate in the conception process (i.e., active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, must agree to use one reliable nonhormonal method of contraception, as listed below, while on study treatment and through study completion
Acceptable forms of contraception include
Intrauterine device (IUD) or intrauterine system
Cervical cap with spermicide
Diaphragm with spermicide
NOTE A: Condoms (male or female) with or without a spermicidal agent are not acceptable, as they are not sufficiently reliable
NOTE B: Participant-reported history is acceptable documentation of menopause (i.e., at least 1 year amenorrheic), hysterectomy, or bilateral oophorectomy or bilateral tubal ligation; these candidates are considered not of reproductive potential and are eligible without the required use of contraception

Exclusion Criteria

Breastfeeding, pregnancy, or plans to become pregnant
Known allergy/sensitivity or any hypersensitivity to components of the study drugs, or their formulations
Presence of any confirmed or probable active TB based on criteria listed in the current AIDS Clinical Trials Group (ACTG) Diagnosis Appendix at screening
History of rifamycin-monoresistant, INH-monoresistent, multi-drug resistant (MDR) or extensively-drug resistant (XDR) TB at any time prior to study entry
Known exposure to rifamycin-monoresistant, INH-monoresistant, MDR- or XDR-TB (e.g., household member of a person with rifamycin-monoresistant, INH monoresistant, MDR- or XDR-TB) at any time prior to study entry by participant self report or medical records
History of peripheral neuropathy Grade 2 according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, July 2017, which can be found on the DAIDS RSC website at <https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.>
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
Acute or serious illness requiring systemic treatment and/or hospitalization within 7 days prior to study entry
Known cirrhosis, a history of decompensated liver disease (ascites, hepatic encephalopathy, or esophageal varices) or current Child Pugh Class B or C hepatic impairment
Note: Refer to the study protocol for Child Pugh scoring and classification table
Initiated, discontinued, or changed doses of drugs that are P-glycoprotein (PGP) inducers, that are P-glycoprotein (PGP) inhibitors,or that are known to have drug interactions with DTG, within 30 days prior to study entry
Note: Refer to the list of prohibited and precautionary medications in the study protocol
Known porphyria at any time prior to study entry
Receipt of any other antiretroviral therapy other than DTG and 2 NRTI within 28 days prior to study entry
Receipt of TAF within 28 days prior to study entry
Documented resistance that may confer reduced susceptibility to DTG, at any time prior to study entry. This includes the following INSTI mutations: Q148 substitutions, T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, G193E/R, or N155H
Clinically suspected INSTI resistance, at any time prior to study entry, as evidenced by prior receipt of INSTI containing ART, during which time two or more HIV-1 RNA levels of >200 copies/mL were observed after having attained virologic suppression to <200 copies/mL and without known interruption
Consumption of >3 alcohol beverages on any day within 30 days prior to entry
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