Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified August 2019 by The HIV Netherlands Australia Thailand Research Collaboration

Sponsor
The HIV Netherlands Australia Thailand Research Collaboration

Collaborator
Faculty of Medical Sciences, Radboud University of Medical Center
Department of Pharmaceutical care, Faculty of Pharmacy, Chiang Mai University
Police General Hospital

Information provided by (Responsible Party)
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier
NCT03727152

First received: October 26, 2018
Last updated: August 8, 2019
Last Verified: August 2019
History of Changes
Purpose

Purpose

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

Condition Intervention Phase
HIV

Drug : generic single tablet TAF/FTC/DTG
Phase 3

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Maintenance of Switching From Protease Inhibitor/Ritonavir to Generic Single Tablet Regimen of Tenofovir Alafenamide/Emtricitibine/Dolutegravir in Virologically Suppressed HIV-infected Adults

Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures

  • 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
Secondary Outcome Measures:
  • Proportion of participants without tolerability failure [ Time Frame: weeks 24 and weeks 48 ]
    Proportion of participants without tolerability failure
  • Cmax of DTG [ Time Frame: weeks 24 and weeks 48 ]
    maximum plasma concentration (Cmax) of DTG 50 mg
  • Tmax of DTG [ Time Frame: weeks 24 and weeks 48 ]
    time to reach maximal concentration (Tmax) of DTG 50 mg
  • 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
  • T1/2 of DTG [ Time Frame: weeks 24 and weeks 48 ]
    elimination half life (T1/2) of DTG 50 mg
  • Ke of DTG [ Time Frame: weeks 24 and weeks 48 ]
    elimination rate constant (Ke) of DTG 50 mg
  • CL of DTG [ Time Frame: weeks 24 and weeks 48 ]
    total plasma clearance (CL) of DTG 50 mg
  • 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).
  • 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).
  • 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)
  • Changes from baseline in insulin [ Time Frame: weeks 24 and weeks 48 ]
    Changes from baseline in insulin
  • Changes from baseline in fasting blood glucose levels [ Time Frame: weeks 24 and weeks 48 ]
    Changes from baseline in fasting blood glucose levels
  • Changes from baseline in renal parameters (creatinine, eGFR) [ Time Frame: weeks 24 and weeks 48 ]
    Changes from baseline in renal parameters (creatinine, eGFR)
  • Changes from baseline in transient elastography results [ Time Frame: weeks 24 and weeks 48 ]
    Changes from baseline in transient elastography results

Estimated Enrollment: 190
Study Start Date: May 1, 2019
Estimated Study Completion Date: December 31, 2021
Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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
Drug: generic single tablet TAF/FTC/DTG

HIV-infected adults who are virologically suppressed and on protease inhibitor/ritonavir are switched to generic single tablet regimen of tenofovir alafenamide/emtricitibine/dolutegravir

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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.
  1. On current ART for at least 6 months prior to study entry
  2. Current ART includes boosted protease inhibitors
  3. 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
  4. HIV-1 plasma RNA <50 copies/mL at screening visit
  5. No prior or current exposure to integrase strand transfer inhibitor (INSTI)
  6. 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
  1. Alcohol or drug abuse that, in the opinion of the investigator, would interfere with completion of study procedures
  2. Any serious illness that, in the opinion of the investigator, would interfere with
completion of study procedures

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03727152

Contacts

Contact:   June Ohata, BS 6626523040 ext 147 juneohata4@gmail.com

Locations

Thailand
HIV-NAT, Thai Red Cross AIDS Research Centre Recruiting
Bangkok, Thailand, 10330
Contact: Sivaporn Gatechompol, MD    662 6523040 ext 171    sivaporn.k@hivnat.org
Principal Investigator: Sivaporn Gatechompol, MD
Police General Hospital Recruiting
Bangkok, Thailand, 10330
Contact: Jirayu Visutranukul, MD    +66 (02) 207 6000    nutjv@yahoo.com
Principal Investigator: Jirayu Visutranukul, MD

Sponsors and Collaborators

The HIV Netherlands Australia Thailand Research Collaboration
Faculty of Medical Sciences, Radboud University of Medical Center
Department of Pharmaceutical care, Faculty of Pharmacy, Chiang Mai University
Police General Hospital

Investigators

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

More Information


Responsible Party: The HIV Netherlands Australia Thailand Research Collaboration  
ClinicalTrials.gov Identifier: NCT03727152   History of Changes  
Other Study ID Numbers: HIV-NAT 256  
Study First Received: October 26, 2018  
Last Updated: August 8, 2019  

Studies a U.S. FDA-regulated Drug Product: No  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:

generic TAF/E/D
virologically suppressed HIV-infected adults
pharmacokinetics (PK) parameters of DTG
psychiatric symptoms
metabolic syndrome
ASCVD risk
liver fibrosis

ClinicalTrials.gov processed this data on May 24, 2020
This information is provided by ClinicalTrials.gov.