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

October 8, 2019 updated by: Scott Letendre, University of California, San Diego

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Not Applicable

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

  • United States
    • California
      • San Diego, California, United States, 92103
        • UC San Diego AntiViral Research Center

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

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)
  • Track B (Currently not taking ART): Off ART for at least 3 months. Prior exposure to TDF and FTC will be allowed but subjects must not have primary genotypic drug resistance mutations to elvitegravir, tenofovir, or emtricitabine (see Exclusion Criteria)
  • Plasma HIV-1 RNA ≥ 5,000c/mL and CD4+ T-cell count ≥200cells/mm3.

Exclusion Criteria:

  • 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

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.
Drug: Stribild
To be administered orally, once daily with food.
Other Names:
  • Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate
Drug: Genvoya
To be administered orally, once daily with food.
Other Names:
  • Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide
Other: 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.
Drug: Genvoya
To be administered orally, once daily with food.
Other Names:
  • Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide
Other: 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.
Drug: Stribild
To be administered orally, once daily with food.
Other Names:
  • Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate
Drug: Genvoya
To be administered orally, once daily with food.
Other Names:
  • Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline
Time Frame: Baseline
Baseline
Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24
Time Frame: Week 24
Week 24
Concentration of Tenofovir in Cerebrospinal Fluid at Baseline
Time Frame: Baseline
Baseline
Concentration of Tenofovir in Cerebrospinal Fluid at Week 24
Time Frame: Week 24
Week 24

Collaborators and Investigators

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

Sponsor

University of California, San Diego

Collaborators

Gilead Sciences
University at Buffalo

Investigators

  • Principal Investigator: Scott Letendre, MD, UCSD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

January 1, 2016

Primary Completion (Actual)

January 18, 2017

Study Completion (Actual)

January 18, 2017

Study Registration Dates

First Submitted

September 24, 2014

First Submitted That Met QC Criteria

September 24, 2014

First Posted (Estimate)

September 29, 2014

Study Record Updates

Last Update Posted (Actual)

October 31, 2019

Last Update Submitted That Met QC Criteria

October 8, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IN-US-236-1266

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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