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

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ClinicalTrials.gov Identifier: NCT03727152
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : August 12, 2019
Sponsor:
Collaborators:
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

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

Condition or disease Intervention/treatment Phase
HIV Drug: generic single tablet TAF/FTC/DTG Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 190 participants
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
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 :
  1. Proportion of participants without tolerability failure [ Time Frame: weeks 24 and weeks 48 ]
    Proportion of participants without tolerability failure

  2. Cmax of DTG [ Time Frame: weeks 24 and weeks 48 ]
    maximum plasma concentration (Cmax) of DTG 50 mg

  3. Tmax of DTG [ Time Frame: weeks 24 and weeks 48 ]
    time to reach maximal concentration (Tmax) of DTG 50 mg

  4. 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

  5. T1/2 of DTG [ Time Frame: weeks 24 and weeks 48 ]
    elimination half life (T1/2) of DTG 50 mg

  6. Ke of DTG [ Time Frame: weeks 24 and weeks 48 ]
    elimination rate constant (Ke) of DTG 50 mg

  7. CL of DTG [ Time Frame: weeks 24 and weeks 48 ]
    total plasma clearance (CL) of DTG 50 mg

  8. 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).

  9. 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).

  10. 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)

  11. Changes from baseline in insulin [ Time Frame: weeks 24 and weeks 48 ]
    Changes from baseline in insulin

  12. Changes from baseline in fasting blood glucose levels [ Time Frame: weeks 24 and weeks 48 ]
    Changes from baseline in fasting blood glucose levels

  13. Changes from baseline in renal parameters (creatinine, eGFR) [ Time Frame: weeks 24 and weeks 48 ]
    Changes from baseline in renal parameters (creatinine, eGFR)

  14. Changes from baseline in transient elastography results [ Time Frame: weeks 24 and weeks 48 ]
    Changes from baseline in transient elastography results



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

  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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727152


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

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

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Responsible Party: The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier: NCT03727152     History of Changes
Other Study ID Numbers: HIV-NAT 256
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019

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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
Additional relevant MeSH terms:
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Ritonavir
HIV Protease Inhibitors
Tenofovir
Dolutegravir
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors