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

• ClinicalTrials.gov Identifier: NCT02251236
• Recruitment Status: Completed
• First Posted: September 29, 2014
• Results First Posted: October 31, 2019
• Last Update Posted: October 31, 2019
• Sponsor: University of California, San Diego
• Collaborators: Gilead Sciences; University at Buffalo
• Information provided by (Responsible Party): Scott Letendre, University of California, San Diego

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV	Drug: Stribild; Drug: Genvoya	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• 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
• Study Start Date: January 2016
• Actual Primary Completion Date: January 18, 2017
• Actual Study Completion Date: January 18, 2017

Arms and Interventions

Arm	Intervention/treatment
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 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
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 Name: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide
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 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

Outcome Measures

Primary Outcome Measures :

1. Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline [ Time Frame: Baseline ]
2. Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24 [ Time Frame: Week 24 ]
3. Concentration of Tenofovir in Cerebrospinal Fluid at Baseline [ Time Frame: Baseline ]
4. Concentration of Tenofovir in Cerebrospinal Fluid at Week 24 [ Time Frame: Week 24 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• 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

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

  Study Documents (Full-Text)

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

Study Protocol and Statistical Analysis Plan  [PDF] July 2, 2014

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Scott Letendre, Associate Professor of Medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT02251236
• Other Study ID Numbers: IN-US-236-1266
• First Posted: September 29, 2014
• Results First Posted: October 31, 2019
• Last Update Posted: October 31, 2019
• Last Verified: October 2019

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; Emtricitabine tenofovir alafenamide; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Elvitegravir; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Integrase Inhibitors