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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 (EpiTAF)

Primary Purpose

HIV-1-infection, Tuberculosis

Status

Completed

Phase

Phase 1

Locations

South Africa

Study Type

Interventional

Intervention

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

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

Phase 3: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz

About this trial

This is an interventional treatment trial for HIV-1-infection focused on measuring Rifampicin, RIF/INH, Tenofovir alafenamide fumarate (TAF), Pharmacokinetics, Intracellular tenofovir-diphosphate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

Charlotte Maxeke Johannesburg Academic Hospital
Wits RHI Yeoville Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tenofovir Alafenamide

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Assessment of maintenance of virological suppression (HIV-1 RNA < 50 copies/mL) while on TAF/RIF

Comparison plasma concentrations of TAF with TDF

Assessment to compare the plasma concentrations of tenofovir of TAF with TDF during coadministration of RIF/INH in TB/HIV-1 coinfected participants

Comparison of IC TFV-DP concentrations of TDF

4. To compare the IC TFV-DP concentrations of TDF with and without coadministration with RIF/INH in TB/HIV-1 coinfected participants

Full Information

NCT ID

NCT04424264

First Posted

June 5, 2020

Last Updated

June 6, 2022

Sponsor

Professor Francois Venter

Collaborators

University of Cape Town

1. Study Identification

Unique Protocol Identification Number

NCT04424264

Brief 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

Acronym

EpiTAF

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Completed

Study Start Date

December 5, 2019 (Actual)

Primary Completion Date

October 30, 2020 (Actual)

Study Completion Date

October 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Professor Francois Venter

Collaborators

University of Cape Town

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV-1-infection, Tuberculosis

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tenofovir Alafenamide

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

Atripla, Rifinah

Intervention Description

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

Intervention Name(s)

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

Other Intervention Name(s)

HepBest, Stocrin

Intervention Description

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

Intervention Name(s)

Phase 3: Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz

Other Intervention Name(s)

Atripla, Rifinah

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

56 days

Secondary Outcome Measure Information:

Title

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

Description

Assessment of maintenance of virological suppression (HIV-1 RNA < 50 copies/mL) while on TAF/RIF

Time Frame

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

Title

Comparison plasma concentrations of TAF with TDF

Description

Assessment to compare the plasma concentrations of tenofovir of TAF with TDF during coadministration of RIF/INH in TB/HIV-1 coinfected participants

Time Frame

56 days

Title

Comparison of IC TFV-DP concentrations of TDF

Description

4. To compare the IC TFV-DP concentrations of TDF with and without coadministration with RIF/INH in TB/HIV-1 coinfected participants

Time Frame

56 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Simiso Sokhela, MBBCh

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Charlotte Maxeke Johannesburg Academic Hospital

City

Johannesburg

State/Province

Gauteng

ZIP/Postal Code

2196

Country

South Africa

Facility Name

Wits RHI Yeoville Clinic

City

Johannesburg

State/Province

Gauteng

Country

South Africa

12. IPD Sharing Statement

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