Clinical trial NCT04424264: The Effect of Rifampicin on the Pharmacokinetics of Intracellular Tenofovir-diphosphate and Tenofovir When Coadministered With Tenofovir Alafenamide Fumarate During the Maintenance Phase of Tuberculosis Treatment in TB/HIV-1 Coinfected Participants
Official title: The Effect of Rifampicin on the Pharmacokinetics of Intracellular Tenofovir-diphosphate and Tenofovir When Coadministered With Tenofovir Alafenamide Fumarate During the Maintenance Phase of Tuberculosis Treatment in TB/HIV-1 Coinfected Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1-infection
Tuberculosis
Keywords: Rifampicin, RIF/INH
Tenofovir alafenamide fumarate (TAF)
Pharmacokinetics
Intracellular tenofovir-diphosphate
Lead sponsor: University of Witwatersrand, South Africa
Sponsor class: OTHER
Collaborators: name: University of Cape Town
First posted: 2020-06-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a pharmacokinetic study investigating the effect of rifampicin on the pharmacokinetics of intracellular tenofovir-diphosphate and plasma tenofovir when coadministered with tenofovir alafenamide fumarate during the maintenance phase of tuberculosis treatment in TB/HIV-1 coinfected participants (EpiTAF)

Detailed description: This is an open-label, sequential, single centre pharmacokinetic (PK) study investigating the effect of rifampicin on the pharmacokinetics of intracellular tenofovir-diphosphate and plasma tenofovir when coadministered with tenofovir alafenamide fumarate during the maintenance phase of tuberculosis treatment in TB/HIV-1 coinfected participants (EpiTAF).

An open-label, sequential, pharmacokinetic (PK) drug-drug interaction study will be conducted in medically stable virologically suppressed HIV-1 infected adults coinfected with TB, who are in the maintenance phase of their TB treatment. After intensive PK evaluation of IC TFV-DP and pTFV, participants will be switched from their standard-of-care tenofovir disoproxil fumarate (TDF)/FTC/EFV regimen, to TAF + 3TC + EFV at the start of the study treatment period. After 28 days each participant will have intensive PK evaluation of IC TFV-DP and pTFV on TAF + 3TC + EFV with rifampicin (RIF). After the second intensive PK assessment is completed, participants will be switched back to TDF/FTC/EFV, with a final intensive PK evaluation of IC TFV-DP and pTFV 8 days after completion of TB treatment, at the final study visit. Eighteen volunteers will be enrolled for a target of 13 participants completing the study.

The study includes screening and enrolment visits, 1 visit on day 28 and an end of study visit 28 days after the end of TB treatment.

Eligibility criteria: Inclusion Criteria:

1. Adult (≥ 18 years old) male or female
2. HIV-1 infected on TDF/FTC/EFV with HIV RNA \< 50 copies/mL in the last three months
3. On TB treatment in the maintenance phase (RIF/INH) with at least one month of TB treatment needed for completion
4. Women of childbearing potential must not be pregnant or breastfeeding, with a negative pregnancy test at screening
5. Women must be postmenopausal, surgically sterile or practicing an effective birth control method (established before and maintained throughout the trial). Women who are not sexually active must agree to use an effective birth control method if they become heterosexually active during the trial
6. Understand the purpose of and procedures required for the study and having confirmed they are willing to participate in the study by signing the informed consent document.

Exclusion Criteria:

1. Weight \< 40 kg
2. Estimated creatinine clearance \< 50 mL/min
3. Any active clinically significant or life-threatening disease (e.g. acute infections, pancreatitis, hepatitis, cardiac dysfunction), medical or psychiatric condition, or findings during screening, that in the investigator's opinion would compromise the safety of the participant or the study outcome, or their ability to comply with the study procedures
4. Chronic medical requirement for any drugs that are known to affect the PK of the study drugs
5. Active drug/alcohol abuser
6. History of allergy or hypersensivity to any of the study drugs
7. Currently enrolled in an investigational drug study or has participated in an investigational drug study within the 4 weeks before screening
8. Unable to comply with study protocol and study protocol restrictions

Primary outcomes:
measure: IC TFV-DP concentrations during coadministration of TAF or TDF with RIF/INH in TB/HIV-1 coinfected participants
timeFrame: 56 days
Secondary outcomes:
measure: Maintenance of irological suppression (HIV-1 RNA < 50 copies/mL)
timeFrame: At screening, day 28, completion of TB and EOS visits
measure: Comparison plasma concentrations of TAF with TDF
timeFrame: 56 days
measure: Comparison of IC TFV-DP concentrations of TDF
timeFrame: 56 days
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits RHI Yeoville Clinic
state: Gauteng
Study officials:
affiliation: Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)
name: Simiso Sokhela, MBBCh
role: PRINCIPAL_INVESTIGATOR
References: