Clinical Trials

MainTitle

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

This study has been completed
Sponsor
University of California, San Diego

Collaborator
Gilead Sciences
University at Buffalo

Information provided by (Responsible Party)
Scott Letendre, University of California, San Diego

ClinicalTrials.gov Identifier
NCT02251236

First received: September 24, 2014
Last updated: May 22, 2017
Last Verified: May 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention
HIV

Drug : Stribild
Drug : Genvoya

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals

Further study details as provided by Scott Letendre, University of California, San Diego:

Primary Outcome Measures

  • Determine the concentrations of elvitegravir, tenofovir and TAF in cerebrospinal fluid (CSF) [ Time Frame: Baseline, week 2 and week 24 ]
Secondary Outcome Measures:
  • Compare tenofovir concentrations in CSF with E/C/F/TDF to tenofovir concentrations in CSF with E/C/F/TAF. [ Time Frame: Baseline, week 2 and week 24 ]
  • Compare changes in drug concentrations in CSF over 24 weeks to changes in drug concentrations in blood [ Time Frame: 6 months ]
  • Compare changes in drug concentrations in CSF over 24 weeks to changes in HIV RNA levels in CSF [ Time Frame: 6 months ]
  • Compare changes in drug concentrations in CSF over 24 weeks to changes in blood-brain barrier (BBB) permeability, as estimated by the CSF-serum albumin ratio [ Time Frame: 6 months ]
  • Compare changes in drug concentrations in CSF over 24 weeks to changes in Montreal Cognitive Assessment (MoCA) scores. [ Time Frame: 6 months ]

Enrollment: 14
Study Start Date: January 2016
Study Completion Date: January 18, 2017
Primary Completion Date: January 18, 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: Track A
Track A is for participants already taking Stribild or Genvoya 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 Name: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate
Drug: Genvoya

To be administered orally, once daily with food.

Other Name: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide
Other: Track B
Track B 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 Name: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate
Drug: Genvoya

To be administered orally, once daily with food.

Other Name: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 60 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

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)
  • 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

    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: NCT02251236

    Locations

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

    Sponsors and Collaborators

    University of California, San Diego
    Gilead Sciences
    University at Buffalo

    Investigators

    Principal Investigator: Scott Letendre, MD UCSD
    More Information

    More Information


    Responsible Party: Scott Letendre, Associate Professor of Medicine, University of California, San Diego  
    ClinicalTrials.gov Identifier: NCT02251236   History of Changes  
    Other Study ID Numbers: IN-US-236-1266  
    Study First Received: September 24, 2014  
    Last Updated: May 22, 2017  

    Keywords provided by Scott Letendre, University of California, San Diego:

    Stribild
    Genvoya
    elvitegravir
    Cerebrospinal Fluid
    HIV

    Additional relevant MeSH terms:
    Tenofovir
    Emtricitabine
    Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
    Cobicistat
    Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

    ClinicalTrials.gov processed this data on December 18, 2017
    This information is provided by ClinicalTrials.gov.