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

Stopped early · Phase 2

Conditions studied: HIV Infection, LTBI

In brief

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.

Key facts

Study ID

NCT04272242

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

37

Starts

2021-02-27

Expected to finish

2021-12-27

Last updated by the study team

2024-09-19

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• NOTE: An existing chest X-ray or CT scan from within 30 days prior to entry can be used as qualifying chest imaging. If chest imaging will be performed for study evaluation (i.e., Screening), then chest X-ray should be performed. A CT scan will be used only if an existing scan is already available and will not be performed as part of study.
• 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.

You may not qualify if…

• 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-monoresistant, 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.

Where it is running

• University of California HIV/AIDS CRS — San Francisco, California, United States
• Houston AIDS Research Team CRS — Houston, Texas, United States
• Gaborone CRS — Gaborone, South-East District, Botswana
• GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS — Port-au-Prince, Haiti
• Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS — Port-au-Prince, Haiti
• Malawi CRS — Lilongwe, Central Malawi, Malawi
• University of Cape Town Lung Institute (UCTLI) CRS — Cape Town, South Africa
• South African Tuberculosis Vaccine Initiative (SATVI) CRS — Cape Town, South Africa
• Thai Red Cross AIDS Research Centre (TRC-ARC) CRS — Pathum Wan, Bangkok, Thailand
• Milton Park CRS — Milton Park, Harare, Zimbabwe

Full record on ClinicalTrials.gov

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