Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals

NCT ID: NCT02251236

Last Updated: 2019-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2017-01-18

Brief Summary

The project will have two tracks, one for participants who are currently taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or E/C/F/tenofovir alafenamide (E/C/F/TDF or E/C/F/TAF) single-tablet regimen* (STR) (Track A) and one for participants who will begin therapy with E/C/F/TDF or E/C/F/TAF STR during the study (Track B).

Participants will take E/C/F/TDF and/or E/C/F/tenofovir alafenamide fumarate (E/C/F/TAF) STR** (if available) for 24 weeks.

*Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate.

**Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide fumarate.

Detailed Description

The proposed project will be a prospective, open-label treatment trial of 14 HIV-infected adults. Participants will be enrolled in two tracks. Track A will enroll participants who have been taking E/C/F/TDF to E/C/F/TAF for at least 12 weeks. Track B will enroll participants who are not taking ART and no prior exposure to elvitegravir and no genotypic drug resistance to any component of E/C/F/TDF to E/C/F/TAF. CSF and blood will be collected twice in Track A (two on-treatment assessments) and three times in Track B (one pre-treatment, two on-treatment assessments). If possible, we plan to time assessments to bridge the transition from E/C/F/TDF to E/C/F/TAF so that all participants will ideally have one CSF collection on each regimen, enabling a paired comparison of tenofovir concentrations between the two tenofovir formulations. We estimate that 28 on-treatment CSF collections will be sufficient to provide a small-sample estimate of the distribution of elvitegravir, tenofovir and TAF into CSF.

Conditions

HIV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stribild Arm

Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.

Group Type: OTHER

Stribild

Intervention Type: DRUG

To be administered orally, once daily with food.

Genvoya

Intervention Type: DRUG

To be administered orally, once daily with food.

Genvoya Arm

Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.

Group Type: OTHER

Genvoya

Intervention Type: DRUG

To be administered orally, once daily with food.

Untreated Arm

Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.

Group Type: OTHER

Stribild

Intervention Type: DRUG

To be administered orally, once daily with food.

Genvoya

Intervention Type: DRUG

To be administered orally, once daily with food.

Interventions

Stribild

To be administered orally, once daily with food.

Intervention Type: DRUG

Genvoya

To be administered orally, once daily with food.

Intervention Type: DRUG

Other Intervention Names

Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate; Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide

Eligibility Criteria

Inclusion Criteria

• Adult men or women aged 18-60 years. Able and willing to provide informed consent.
• Presence of HIV-1 infection as documented by a licensed ELISA test kit and confirmed by Western blot or HIV RNA.
• Track A (Currently taking E/C/F/TDF or E/C/F/TAF): Taking E/C/F/TDF or E/C/F/TAF for at least 3 months prior to screening and undetectable plasma HIV-1 RNA (≤ 40 copies/mL)

Exclusion Criteria

• Plasma HIV-1 RNA ≥ 5,000c/mL and CD4+ T-cell count ≥200cells/mm3.

• Track B: Presence of primary drug resistance mutations for EVG, tenofovir, or emtricitabine.
• Use of drugs of abuse or alcohol which would interfere with adherence or completion of this study. While on-study, subjects will be instructed not to consume alcohol for 48 hours prior to pharmacokinetic sampling days.
• 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 subjects ability to participate in the protocol.
• Use of prohibited protocol-specified drugs, prescription or over-the-counter, within 14 days prior to study entry.
• Bleeding abnormality or other contraindication to lumbar puncture.
• Moderate or severe cognitive impairment by history or based on Montreal Cognitive Assessment.
• Hepatitis B surface antigen (HBsAg) positive (Positive anti-HBs antibody and negative HBsAg results are acceptable)
• Hepatitis C antibody (HCV Ab) positive
• 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/mm3;

3. AST (SGOT) or ALT (SGPT) > 1.5 x the upper limit of normal (ULN);

4. Estimated GFR<70 ml/min

5. Weight less than 50 kg

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University at Buffalo

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Scott Letendre

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Scott Letendre, MD

Role: PRINCIPAL_INVESTIGATOR

UCSD

Locations

UC San Diego AntiViral Research Center

San Diego, California, United States

Countries

United States

References

Ma Q, Ocque AJ, Morse GD, Sanders C, Burgi A, Little SJ, Letendre SL. Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid. Clin Infect Dis. 2020 Aug 14;71(4):982-988. doi: 10.1093/cid/ciz926.

Reference Type: DERIVED

PMID: 31560741 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IN-US-236-1266

Identifier Type: -

Identifier Source: org_study_id