Bictegravir in the Elderly Living With HIV (BICEP)

NCT ID: NCT05064020

Last Updated: 2024-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

162 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-08-01

Study Completion Date

2024-12-31

Brief Summary

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This is a prospective, open-label, single center, post-approval and post-marketing study. Current national guideline recommends an integrase strand inhibitors (INSTI) in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) as standard of therapy for HIV-1 infected patients. INSTI-based regimen may require a potent CYP3A inhibitor such as cobicistat to increase INSTI's plasma concentration and prolongs half-life. However, co-administration with a CYP3A inhibitor may increase the risk of drug-drug interactions. A novel INSTI, bictegravir, does not need a booster for pharmacokinetic enhancement.

Hypothesis: switching HIV-1 infected patients from booster containing regimen to bictegravir based regimen would decrease the risk of drug-drug interactions caused by a booster and improve quality of life and adherence.

Detailed Description

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Antiretroviral treatment consisting of integrase strand inhibitors (INSTI) in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) has become the standard of therapy for HIV-1 infected patients (2017 DHHS Guidelines). The development and advancement of such therapy have resulted in improved prognosis, allowing a larger proportion of patients in United States (\> 50%) with HIV-1 infection to be 50 years of age or older, which is defined by the CDC as "older adults". A novel INSTI, bictegravir (BIC), has been recently approved by FDA, available in a fixed dose combination with emtricitabine (FTC) and tenofovir alafenamide (TAF) as a novel single-tablet regimen (STR), BIKTARVY®. Similar to other INSTI, BIC prevents HIV replication by inhibiting HIV integration into the host cell. In vitro studies have shown its selectivity against HIV-1 infected cells with a low cytotoxic profile.

Elvitegravir, boosted with cobicistat, is currently available as part of a single-tablet formulation with FTC and TAF (GenvoyaTM) or with FTC and TDF (StribildTM). Unlike ritonavir, cobicistat has no antiretroviral activity, but has potent inhibitory effects on CYP3A44. Elvitegravir is primarily metabolized by CYP3A4 and its co-administration with cobicistat boosts elvitegravir plasma concentration and prolongs its half-life4. Concurrent use of a potent CYP3A4 inhibitor, e.g., cobicistat, with medications that are metabolized by CYP3A4 can significantly increase the risk of drug-drug interactions. With an increase in the average survivability age of HIV-infected patients, chances of polypharmacy due to multimorbidity, a term used to define the presence of two or more concurrent chronic medical conditions, increases. Two studies have demonstrated that older HIV+ individuals engaged in polypharmacy are more likely to experience potential drug-drug interactions (PDDI). Many chronic medications such as antidepressants, HMG-CoA reductase inhibitors (statins), and cardiovascular medications are metabolized by CYP3A4. Concurrent administration of these medications with GenvoyaTM and StribildTMcan lead to increases in PDDI. Such interactions can result in more adverse drug reactions, drug-related toxicity of narrow therapeutic index drugs, and variations in the efficacy of concurrent medications. However, unlike elvitegravir, BIC does not require a booster such as cobicistat for pharmacokinetic enhancement. Its use can result in reductions in PDDI caused by cobicistat in adults with polypharmacy. This can improve quality of life in general, adherence and can directly avoid DDI-related adverse effects.

Although antiretroviral therapy (ART), when used concurrently with certain medications, has an increased risk of PDDI, studies have suggested a low DDI profile of BIC. In this study, such benefits of bictegravir will be assessed through the evaluation of polypharmacy, PDDI, health-related quality of life, and adherence of HIV-infected subjects.

BIC/FTC/TAF related adverse drug events are possible in the study. Due to BIC's recent FDA approval, a comprehensive list on the possible adverse drug events has become available. Common side effects reported in clinical phase II and phase III studies include diarrhea, nausea, and headache. Serious adverse events, including lactic acidosis, severe hepatomegaly have been reported with nucleoside reverse transcriptase inhibitors, but are uncommon. The standard regimen of BIC/FTC/TAF will be used; if a regimen change occurs, participation in the study will be discontinued. Participants will be carefully screened and those with pre-conditions, such as morbid obesity, hepatitis B virus, hepatitis C virus co-infection will be documented in the study.

Conditions

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HIV-1-infection

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Polypharmacy

Polypharmacy: patient is using five or more medications will be considered polypharmacy.

Subjects having polypharmacy condition with taking Elvitegravir/Cobicistat/Emtricitabine/Tenofovir/Alafenamide 150MG-150MG-200MG-10MG Oral Tablet \[Genvoya\] or Elevitegravir/Cobicistat/Emtricitabine/Tenofovir disoproxil fumarate 150MG-150MG-200MG-300MG Oral Tablet \[Stribild\] will switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet \[BIKTARVY\]

Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet [BIKTARVY]

Intervention Type DRUG

Administer BIC/FTC/TAF 50/200/25 mg tablet by mouth once a day from day 1 to168.

Nonpolypharmacy

Nonpolypharmacy: patient is using less than five medications will be considered nonpolypharmacy

Nonpolypharmacy Subjects taking Elvitegravir/Cobicistat/Emtricitabine/Tenofovir/Alafenamide 150MG-150MG-200MG-10MG Oral Tablet \[Genvoya\] or Elevitegravir/Cobicistat/Emtricitabine/Tenofovir disoproxil fumarate 150MG-150MG-200MG-300MG Oral Tablet \[Stribild\] will switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet \[BIKTARVY\]

Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet [BIKTARVY]

Intervention Type DRUG

Administer BIC/FTC/TAF 50/200/25 mg tablet by mouth once a day from day 1 to168.

Interventions

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Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet [BIKTARVY]

Administer BIC/FTC/TAF 50/200/25 mg tablet by mouth once a day from day 1 to168.

Intervention Type DRUG

Other Intervention Names

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Biktarvy BIC/FTC/TAF

Eligibility Criteria

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Inclusion Criteria

* Adult individuals \> 18 years of age.
* Able and willing to provide informed/signed consent.
* Presence of HIV-1 infection as documented by a licensed ELISA test kit and confirmed by Western blot or HIV RNA.
* Current antiretroviral therapy, Genvoya or Stribild for HIV-1 infection.
* At least 1 or more concurrent prescription medication.
* HIV VL \< 50 for over 6 months, no current OI, no cancers

Exclusion Criteria

* Use of drugs of abuse or alcohol which would interfere with adherence or completion of this study.
* Current antiretroviral therapy other than GenvoyaTM or StribildTM for HIV-1 infection.
* Pregnancy or breast-feeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to study entry and day of entry.
* Chronic, severe, or other medical conditions that, in the opinion of the investigator, would interfere with the subject's ability to participate in the protocol.
* Use of prohibited protocol-specified drugs, prescription or over-the-counter medication (see Section 6.4.2) within 14 days prior to study entry.
* Moderate or severe cognitive impairment by history that, in the opinion of the investigator, would interfere with the subject's ability to participate in the protocol
* Laboratory parameters documented within 21 days prior to study entry that would increase the risk for adverse events:

1. Hemoglobin \< 12.5 g/dL for men; \< 11.5 g/dL for women;
2. Platelet count \< 100,000 platelets/mm 3;
3. AST (SGOT) or ALT (SGPT) \> 1.5 x the upper limit of normal (ULN);
4. Estimated GFR \< 30 ml/min
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

State University of New York at Buffalo

OTHER

Sponsor Role lead

Responsible Party

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Qing Ma, PharmD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Qing Ma, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

University at Buffalo

Locations

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Evergreen Health

Buffalo, New York, United States

Site Status

Countries

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United States

References

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Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar ES, Wohl D, Rockstroh J, Wei X, Custodio J, White K, Martin H, Cheng A, Quirk E. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2063-2072. doi: 10.1016/S0140-6736(17)32299-7. Epub 2017 Aug 31.

Reference Type BACKGROUND
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Gleason LJ, Luque AE, Shah K. Polypharmacy in the HIV-infected older adult population. Clin Interv Aging. 2013;8:749-63. doi: 10.2147/CIA.S37738. Epub 2013 Jun 21.

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Sax PE, Pozniak A, Arribas J, et al. Phase 3 randomized, controlled, clinical trial of bictegravir coformulated with FTC/TAF in a fixed-dose combination vs dolutegravir + FTC/TAF in treatment-naïve HIV-1-positive adults: Week 48 results. International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2017; Paris, France. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2017.

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Provided Documents

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Document Type: Study Protocol

View Document

Related Links

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http://www.natap.org/2017/IAS/IAS_39.htm

The link to the Citation that didn't find a PubMed ID

https://www.biktarvyhcp.com/dosing-administration/dosing

The information related to Biktarvy package insert

Other Identifiers

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STUDY00003629

Identifier Type: -

Identifier Source: org_study_id

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