Elvitegravir (EVG) Cerebrospinal Fluid (CSF) Pharmacokinetics in HIV-Infected Individuals
Study Details
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 |
|---|---|---|
| N/A |
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
Arms and Interventions
| 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:
Drug: Genvoya
To be administered orally, once daily with food.
Other Names:
|
| 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:
|
| 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:
Drug: Genvoya
To be administered orally, once daily with food.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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]
Eligibility Criteria
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:
-
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
-
Weight less than 50 kg
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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)
More Information
Publications
None provided.- IN-US-236-1266
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Stribild Arm | Genvoya Arm | Untreated Arm |
|---|---|---|---|
| Arm/Group Description | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | 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. Genvoya: To be administered orally, once daily with food. | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. |
| Period Title: Overall Study | |||
| STARTED | 9 | 5 | 0 |
| COMPLETED | 9 | 5 | 0 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Stribild Arm | Genvoya Arm | Untreated Arm | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | 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. Genvoya: To be administered orally, once daily with food. | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | Total of all reporting groups |
| Overall Participants | 9 | 5 | 0 | 14 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
34
|
45
|
34.5
|
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
1
11.1%
|
0
0%
|
1
Infinity
|
|
| Male |
8
88.9%
|
5
100%
|
13
Infinity
|
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
NaN
|
|
| Asian |
0
0%
|
0
0%
|
0
NaN
|
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
NaN
|
|
| Black or African American |
1
11.1%
|
1
20%
|
2
Infinity
|
|
| White |
8
88.9%
|
4
80%
|
12
Infinity
|
|
| More than one race |
0
0%
|
0
0%
|
0
NaN
|
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
NaN
|
|
| Plasma HIV RNA ≤ 40 copies/mL (Count of Participants) | ||||
| Count of Participants [Participants] |
9
100%
|
5
100%
|
14
Infinity
|
|
| CD4+ T-cell Count (cells/µL) [Median (Full Range) ] | ||||
| Median (Full Range) [cells/µL] |
601
|
784
|
717
|
|
Outcome Measures
| Title | Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline |
|---|---|
| Description | |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| No participants enrolled in the Untreated Arm |
| Arm/Group Title | Stribild Arm | Genvoya Arm | Untreated Arm |
|---|---|---|---|
| Arm/Group Description | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | 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. Genvoya: To be administered orally, once daily with food. | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. |
| Measure Participants | 9 | 5 | 0 |
| Median (Full Range) [ng/mL] |
4.3
|
2.72
|
| Title | Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24 |
|---|---|
| Description | |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| No participants enrolled in the Untreated Arm |
| Arm/Group Title | Stribild Arm | Genvoya Arm | Untreated Arm |
|---|---|---|---|
| Arm/Group Description | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | 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. Genvoya: To be administered orally, once daily with food. | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. |
| Measure Participants | 9 | 5 | 0 |
| Median (Full Range) [ng/mL] |
5.90
|
3.09
|
| Title | Concentration of Tenofovir in Cerebrospinal Fluid at Baseline |
|---|---|
| Description | |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| No participants enrolled in the Untreated Arm |
| Arm/Group Title | Stribild Arm | Genvoya Arm | Untreated Arm |
|---|---|---|---|
| Arm/Group Description | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | 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. Genvoya: To be administered orally, once daily with food. | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. |
| Measure Participants | 9 | 5 | 0 |
| Median (Full Range) [ng/mL] |
3.03
|
0.49
|
| Title | Concentration of Tenofovir in Cerebrospinal Fluid at Week 24 |
|---|---|
| Description | |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| No participants enrolled in the Untreated Arm |
| Arm/Group Title | Stribild Arm | Genvoya Arm | Untreated Arm |
|---|---|---|---|
| Arm/Group Description | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | 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. Genvoya: To be administered orally, once daily with food. | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. |
| Measure Participants | 9 | 5 | 0 |
| Median (Full Range) [ng/mL] |
0.507
|
0.481
|
Adverse Events
| Time Frame | 24 weeks | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | No participants enrolled in the Untreated Arm so the number of participants at risk is zero | |||||
| Arm/Group Title | Stribild Arm | Genvoya Arm | Untreated Arm | |||
| Arm/Group Description | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | 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. Genvoya: To be administered orally, once daily with food. | 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. Stribild: To be administered orally, once daily with food. Genvoya: To be administered orally, once daily with food. | |||
All Cause Mortality |
||||||
| Stribild Arm | Genvoya Arm | Untreated Arm | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/5 (0%) | 0/0 (NaN) | |||
Serious Adverse Events |
||||||
| Stribild Arm | Genvoya Arm | Untreated Arm | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/9 (11.1%) | 1/5 (20%) | 0/0 (NaN) | |||
| Nervous system disorders | ||||||
| Headache, Grade 3 | 0/9 (0%) | 0 | 1/5 (20%) | 1 | 0/0 (NaN) | 0 |
| Renal and urinary disorders | ||||||
| Creatinine Clearance Reduction, Grade 3 | 1/9 (11.1%) | 2 | 0/5 (0%) | 0 | 0/0 (NaN) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Stribild Arm | Genvoya Arm | Untreated Arm | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/9 (44.4%) | 5/5 (100%) | 0/0 (NaN) | |||
| Blood and lymphatic system disorders | ||||||
| Leukopenia, Grade 1 | 0/9 (0%) | 0 | 1/5 (20%) | 1 | 0/0 (NaN) | 0 |
| Endocrine disorders | ||||||
| Elevated Serum Glucose, Grade 1 | 1/9 (11.1%) | 2 | 1/5 (20%) | 1 | 0/0 (NaN) | 0 |
| Hepatobiliary disorders | ||||||
| Elevated Hepatic Alanine Transaminase, Grade 1 | 1/9 (11.1%) | 2 | 1/5 (20%) | 1 | 0/0 (NaN) | 0 |
| Elevated Hepatic Aspartate Transaminase, Grade 2 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/0 (NaN) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Elevated Lactic Acid, Grade 1 | 1/9 (11.1%) | 1 | 1/5 (20%) | 1 | 0/0 (NaN) | 0 |
| Elevated Creatine Kinase, Grade 2 | 0/9 (0%) | 0 | 1/5 (20%) | 1 | 0/0 (NaN) | 0 |
| Renal and urinary disorders | ||||||
| Elevated Serum Bicarbonate, Grade 1 | 0/9 (0%) | 0 | 1/5 (20%) | 2 | 0/0 (NaN) | 0 |
| Elevated Serum Creatinine, Grade 1 or 2 | 1/9 (11.1%) | 3 | 1/5 (20%) | 1 | 0/0 (NaN) | 0 |
| Hypernatremia, Grade 2 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/0 (NaN) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Scott Letendre, Principal Investigator |
|---|---|
| Organization | University of California, San Diego |
| Phone | 6195438080 |
| sletendre@ucsd.edu |
- IN-US-236-1266