Switching From Protease Inhibitor/Ritonavir to Generic Single Tablet Regimen of Tenofovir Alafenamide/Emtricitibine/Dolutegravir

Maintenance of Switching From Protease Inhibitor/Ritonavir to Generic Single Tablet Regimen of Tenofovir Alafenamide/Emtricitibine/Dolutegravir in Virologically Suppressed HIV-infected Adults

This is a phase III, multicenter, open-label, single-arm study of 190 virologically suppressed HIV-infected adults

Study Overview

Status

Completed

Conditions

Detailed Description

The fundamental principle of regimen switching is to maintain viral suppression without jeopardizing future treatment options. The reasons to consider regimen switching in the viral suppressed population are to simplify the regimen by reducing the pill burden and dosing frequency, to increase the tolerability, reduce the adverse effects as well as long-term toxicities, to prevent drug-to-drug interactions and to avoid the dietary requirements.

Generic TAF/E/D (tenofovir alafenamide 25mg/emtricitabine 200mg/dolutegravir 50 mg), a single-tablet once daily regimen, will be an affordable regimen with the potential characteristics such as reduced pill burden, less drug to drug interaction and toxicities. The generic form (Mylan) is recently received the tentative approval from the U.S. Food and Drug Administration (FDA) under the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Whether DTG-containing regimen is a better option than protease inhibitors among resource-limited settings during the decisions for second-line treatment options, is needed to be evaluated.

All participants will be switched from their pre-study ART regimen to a single tablet regimen (STR) of TAF/FTC/DTG 25/200/50mg once daily.

Study Type

Interventional

Enrollment (Actual)

170

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bangkok, Thailand, 10330
        • HIV-NAT, Thai Red Cross AIDS Research Centre
      • Bangkok, Thailand, 10330
        • Police General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Documented HIV-1 infection
  2. Aged ≥18 years old
  3. Female participant may be eligible to participate if she:

    is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea or >=54 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, is of child-bearing potential, with a negative pregnancy test at both Screening and week 0 and agrees to use one of the protocol-defined methods of contraception to avoid pregnancy.

  4. On current ART for at least 6 months prior to study entry
  5. Current ART includes boosted protease inhibitors
  6. No more than one HIV-1 plasma RNA >50 copies/mL and <200 copies/L (only one 'blip') in the past 6 months with a subsequent HIV-1 plasma RNA <50 copies/mL
  7. HIV-1 plasma RNA <50 copies/mL at screening visit
  8. No prior or current exposure to integrase strand transfer inhibitor (INSTI)
  9. Have signed the informed consent form

Exclusion Criteria:

  1. Breastfeeding female
  2. Pregnancy or positive UPT at screening
  3. Calculated creatinine clearance as estimated by Cockcroft-Gault equation (CrCl) <60 mL/min,
  4. Alanine aminotransferase (ALT) >2.5 x ULN,
  5. Concomitant use of any of the following medications:

(1) aluminum and magnesium-containing antacids, proton-pump inhibitors (2) anticonvulsants: carbamazepine, oxcarbamazepine, phenobarbital, phenytoin (3) antimycobacterials: rifabutin, rifampin, rifapentine (4) St. John's wort

6. Alcohol or drug abuse that, in the opinion of the investigator, would interfere with completion of study procedures

7. Any serious illness that, in the opinion of the investigator, would interfere with completion of study procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: generic single tablet regimen of tenofovir alafenamide/e
HIV infected adults currently on protease inhibitor/ritonavir will switch to use generic single tablet regimen of tenofovir alafenamide/emtricitibine/dolutegravir to see if the single tablet can continue to suppress viral replication and be used as a maintenance regimen
HIV-infected adults who are virologically suppressed and on protease inhibitor/ritonavir are switched to generic single tablet regimen of tenofovir alafenamide/emtricitibine/dolutegravir

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of subjects with undetectable viral load
Time Frame: 48 weeks
Proportion of participants with plasma HIV-1 RNA <50 copies/mL using Snapshot algorithm at week 48
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants without tolerability failure
Time Frame: weeks 24 and weeks 48
Proportion of participants without tolerability failure
weeks 24 and weeks 48
Cmax of DTG
Time Frame: weeks 24 and weeks 48
maximum plasma concentration (Cmax) of DTG 50 mg
weeks 24 and weeks 48
Tmax of DTG
Time Frame: weeks 24 and weeks 48
time to reach maximal concentration (Tmax) of DTG 50 mg
weeks 24 and weeks 48
AUC of DTG
Time Frame: weeks 24 and weeks 48
area under the curve of a plasma concentration versus time profile (AUC) of DTG 50 mg
weeks 24 and weeks 48
T1/2 of DTG
Time Frame: weeks 24 and weeks 48
elimination half life (T1/2) of DTG 50 mg
weeks 24 and weeks 48
Ke of DTG
Time Frame: weeks 24 and weeks 48
elimination rate constant (Ke) of DTG 50 mg
weeks 24 and weeks 48
CL of DTG
Time Frame: weeks 24 and weeks 48
total plasma clearance (CL) of DTG 50 mg
weeks 24 and weeks 48
Anxiety at baseline will be compared to level of anxiety at weeks 24 and weeks 48.
Time Frame: weeks 24 and weeks 48
Anxiety at baseline will be compared to anxiety level at weeks 24 and weeks 48. Anxiety will be assessed using Hospital Anxiety and Depression Scale (HADS). There are 7 different items that assess the level of anxiety of the participants based on a four-point grading scale specific for each item assessed (i.e., I feel tense or 'wound up'; 0 = not at all; 1 = from time to time, occasionally; 2 = a lot of the time; 3 = most of the time). If the total score is between 0-7, then this is considered to be normal. If the total score is between 8-10, then this is considered borderline abnormal (borderline case). If the total score is between 11-21, then this is considered abnormal (case).
weeks 24 and weeks 48
Depression at baseline will be compared to depression level at weeks 24 and weeks 48.
Time Frame: weeks 24 and weeks 48
Depression at baseline will be compared to depression level at weeks 24 and weeks 48. Depression will be assessed using Hospital Anxiety and Depression Scale (HADS). There are 7 different items that assess the level of depression of the participants based on a four-point grading scale specific for each item assessed (i.e., I still enjoy the things I used to enjoy; 0 = definitely as much; 1 = not quite so much; 2 = only a little; 3 = hardly at all). If the total score is between 0-7, then this is considered to be normal. If the total score is between 8-10, then this is considered borderline abnormal (borderline case). If the total score is between 11-21, then this is considered abnormal (case).
weeks 24 and weeks 48
Changes from baseline in fasting lipid profiles
Time Frame: weeks 24 and weeks 48
Changes from baseline in fasting lipid profiles (HDL, LDL, cholesterol, TG)
weeks 24 and weeks 48
Changes from baseline in insulin
Time Frame: weeks 24 and weeks 48
Changes from baseline in insulin
weeks 24 and weeks 48
Changes from baseline in fasting blood glucose levels
Time Frame: weeks 24 and weeks 48
Changes from baseline in fasting blood glucose levels
weeks 24 and weeks 48
Changes from baseline in renal parameters (creatinine, eGFR)
Time Frame: weeks 24 and weeks 48
Changes from baseline in renal parameters (creatinine, eGFR)
weeks 24 and weeks 48
Changes from baseline in transient elastography results
Time Frame: weeks 24 and weeks 48
Changes from baseline in transient elastography results
weeks 24 and weeks 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Sivaporn Gatechompol, MD, The HIV Netherlands Australia Thailand Research Collaboration

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Actual)

April 4, 2023

Study Completion (Actual)

April 4, 2023

Study Registration Dates

First Submitted

October 26, 2018

First Submitted That Met QC Criteria

October 30, 2018

First Posted (Actual)

November 1, 2018

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 26, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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