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

NCT ID: NCT04424264

Last Updated: 2022-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-05
• Study Completion Date: 2020-10-30

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.

Conditions

HIV-1-infection; Tuberculosis

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tenofovir Alafenamide

TAF 25 mg once-daily administered with RIF/INH 600\*/300mg

Group Type: EXPERIMENTAL

Phase 1: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz coadministered with Rifampicin/Isoniazid

Intervention Type: DRUG

TDF/FTC/EFV 300/200/600 mg once daily plus RIF/INH 600\*/300 mg daily from screening until enrolment (days -15 to 0)

Phase 2: Tenofovir alafenamide/Lamivudine/Efavirenz coadministered with Rifampicin/Isoniazid

Intervention Type: DRUG

TAF 25 mg + 3TC 300 mg + EFV 600 mg once daily plus RIF/INH 600/\*300 mg daily (days 1 to ≤ 56)

Phase 3: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz

Intervention Type: DRUG

TDF/FTC/EFV 300/200/600 mg once daily. RIF/INH 600mg \<70kg, 750mg \>70kg

Interventions

Phase 1: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz coadministered with Rifampicin/Isoniazid

TDF/FTC/EFV 300/200/600 mg once daily plus RIF/INH 600\*/300 mg daily from screening until enrolment (days -15 to 0)

Intervention Type: DRUG

Phase 2: Tenofovir alafenamide/Lamivudine/Efavirenz coadministered with Rifampicin/Isoniazid

TAF 25 mg + 3TC 300 mg + EFV 600 mg once daily plus RIF/INH 600/\*300 mg daily (days 1 to ≤ 56)

Intervention Type: DRUG

Phase 3: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz

TDF/FTC/EFV 300/200/600 mg once daily. RIF/INH 600mg \<70kg, 750mg \>70kg

Intervention Type: DRUG

Other Intervention Names

Atripla; Rifinah; HepBest; Stocrin; Atripla; Rifinah

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cape Town

OTHER

Sponsor Role: collaborator

Professor Francois Venter

OTHER

Sponsor Role: lead

Responsible Party

Professor Francois Venter

Divisional Director of Ezintsha

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Simiso Sokhela, MBBCh

Role: PRINCIPAL_INVESTIGATOR

Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)

Locations

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, Gauteng, South Africa

Wits RHI Yeoville Clinic

Johannesburg, Gauteng, South Africa

Countries

South Africa

Other Identifiers

WRHI061

Identifier Type: -

Identifier Source: org_study_id