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

NCT04424264 | Completed Phase 1 DMC

• 1 other identifier: WRHI061
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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)

Conditions

HIV-1-infection; Tuberculosis

Keywords

Rifampicin, RIF/INH; Tenofovir alafenamide fumarate (TAF); Pharmacokinetics; Intracellular tenofovir-diphosphate

Outcome Measures

Primary Outcomes (1)

• IC TFV-DP concentrations during coadministration of TAF or TDF with RIF/INH in TB/HIV-1 coinfected participants

  Intracellular and plasma TFV-DP concentrations measured during coadministration of TAF or TDF with RIF/INH

  56 days

Secondary Outcomes (3)

• Maintenance of irological suppression (HIV-1 RNA < 50 copies/mL)

  At screening, day 28, completion of TB and EOS visits

• Comparison plasma concentrations of TAF with TDF

  56 days

• Comparison of IC TFV-DP concentrations of TDF

  56 days

Study Arms (1)

Tenofovir Alafenamide

EXPERIMENTAL

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

Drug: Phase 1: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz coadministered with Rifampicin/Isoniazid; Drug: Phase 2: Tenofovir alafenamide/Lamivudine/Efavirenz coadministered with Rifampicin/Isoniazid; Drug: Phase 3: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz

Interventions

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

Also known as: Atripla, Rifinah

Tenofovir Alafenamide

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

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

Also known as: HepBest, Stocrin

Tenofovir Alafenamide

Phase 3: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz DRUG

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

Also known as: Atripla, Rifinah

Tenofovir Alafenamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (≥ 18 years old) male or female
• HIV-1 infected on TDF/FTC/EFV with HIV RNA \< 50 copies/mL in the last three months
• On TB treatment in the maintenance phase (RIF/INH) with at least one month of TB treatment needed for completion
• Women of childbearing potential must not be pregnant or breastfeeding, with a negative pregnancy test at screening
• 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
• 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.

You may not qualify if:

• Weight \< 40 kg
• Estimated creatinine clearance \< 50 mL/min
• 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
• Chronic medical requirement for any drugs that are known to affect the PK of the study drugs
• Active drug/alcohol abuser
• History of allergy or hypersensivity to any of the study drugs
• Currently enrolled in an investigational drug study or has participated in an investigational drug study within the 4 weeks before screening
• Unable to comply with study protocol and study protocol restrictions

Sponsors & Collaborators

• Professor Francois Venter: lead
• University of Cape Town: collaborator

Study Sites (2)

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, Gauteng, 2196, South Africa

Location

Wits RHI Yeoville Clinic

Johannesburg, Gauteng, South Africa

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; efavirenz

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Simiso Sokhela, MBBCh

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Divisional Director of Ezintsha

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 9, 2020
• Study Start: December 5, 2019
• Primary Completion: October 30, 2020
• Study Completion: October 30, 2020
• Last Updated: June 7, 2022

Record last verified: 2022-06

Locations

ZA (2)