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

NCT02251236 | Completed Results DMC

• 1 other identifier: IN-US-236-1266
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV

Keywords

Stribild; Genvoya; elvitegravir; Cerebrospinal Fluid; HIV

Outcome Measures

Primary Outcomes (4)

• Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline

  Baseline

• Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24

  Week 24

• Concentration of Tenofovir in Cerebrospinal Fluid at Baseline

  Baseline

• Concentration of Tenofovir in Cerebrospinal Fluid at Week 24

  Week 24

Study Arms (3)

Stribild Arm

OTHER

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; Drug: Genvoya

Genvoya Arm

OTHER

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

Untreated Arm

OTHER

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; Drug: Genvoya

Interventions

Stribild DRUG

To be administered orally, once daily with food.

Also known as: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate

Stribild Arm; Untreated Arm

Genvoya DRUG

To be administered orally, once daily with food.

Also known as: Co-formulated elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide

Genvoya Arm; Stribild Arm; Untreated Arm

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• Hemoglobin \< 12.5 g/dL for men; \< 11.5 g/dL for women;
• Platelet count \< 100,000 platelets/mm3;
• AST (SGOT) or ALT (SGPT) \> 1.5 x the upper limit of normal (ULN);
• Estimated GFR\<70 ml/min

Sponsors & Collaborators

• University of California, San Diego: lead
• Gilead Sciences: collaborator
• University at Buffalo: collaborator

Study Sites (1)

UC San Diego AntiViral Research Center

San Diego, California, 92103, United States

Location

Related Publications (1)

• 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.

  PMID: 31560741 DERIVED

MeSH Terms

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Cobicistat; Emtricitabine; Tenofovir; tenofovir alafenamide

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Scott Letendre, Principal Investigator
• Organization: University of California, San Diego

sletendre@ucsd.edu

6195438080

Study Officials

• Scott Letendre, MD

  UCSD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: September 24, 2014
• First Posted: September 29, 2014
• Study Start: January 1, 2016
• Primary Completion: January 18, 2017
• Study Completion: January 18, 2017
• Last Updated: October 31, 2019
• Results First Posted: October 31, 2019

Record last verified: 2019-10

Locations

US (1)