Trial Outcomes & Findings for The Compartmental Biology of HIV in the Male Genital Tract (NCT NCT02638493)

NCT ID: NCT02638493

Last Updated: 2017-07-24

Results Overview

Samples will be analyzed for drug concentrations at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate clearance from semen from a 300mg dose of tenofovir.

Recruitment status

COMPLETED

Target enrollment

26 participants

Primary outcome timeframe

Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose

Results posted on

2017-07-24

Participant Flow

All participants were recruited at the University of North Carolina at Chapel Hill and surrounding areas, through Institutional Review Board (IRB)-approved advertisements.

Participants interested in the study were pre-screened for eligibility using an IRB-approved questionnaire.

Participant milestones

Participant milestones
Measure	HIV Positive TDF/FTC 8 HIV positive men taking TDF/FTC (Tenofovir Disoproxil Fumarate/Emtricitabine) as treatment	HIV Negative 8 HIV negative men taking TDF/FTC (Tenofovir Disoproxil Fumarate/Emtricitabine) as pre-exposure prophylaxis	HIV Positive TAF 8 HIV positive men taking TAF (Tenofovir Alafenamide) as treatment
Overall Study STARTED	10	8	8
Overall Study COMPLETED	8	8	8
Overall Study NOT COMPLETED	2	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	HIV Positive TDF/FTC 8 HIV positive men taking TDF/FTC (Tenofovir Disoproxil Fumarate/Emtricitabine) as treatment	HIV Negative 8 HIV negative men taking TDF/FTC (Tenofovir Disoproxil Fumarate/Emtricitabine) as pre-exposure prophylaxis	HIV Positive TAF 8 HIV positive men taking TAF (Tenofovir Alafenamide) as treatment
Overall Study Inability to provide semen samples	2	0	0

Baseline Characteristics

The Compartmental Biology of HIV in the Male Genital Tract

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	24 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	36.5 years n=5 Participants	30.5 years n=7 Participants	45.5 years n=5 Participants	36.5 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment United States	8 participants n=5 Participants	8 participants n=7 Participants	8 participants n=5 Participants	24 participants n=4 Participants

PRIMARY outcome

Timeframe: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose

Samples will be analyzed for drug concentrations at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate clearance from semen from a 300mg dose of tenofovir.

Outcome measures

Outcome measures
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment
Semen Clearance (CL) of Tenofovir	33.88 L/hr Interval 18.86 to 65.26	51.21 L/hr Interval 19.18 to 77.79	5.65 L/hr Interval 3.23 to 7.23

PRIMARY outcome

Timeframe: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose

Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate clearance from semen from a 200mg dose of emtricitabine.

Outcome measures

Outcome measures
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment
Semen Clearance (CL) of Emtricitabine	5.91 L/hr Interval 5.43 to 8.28	8.72 L/hr Interval 4.95 to 12.3	7.12 L/hr Interval 3.91 to 11.09

PRIMARY outcome

Timeframe: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose

Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of tenofovir diphosphate, an intracellular metabolite of tenofovir, from seminal mononuclear cells, following a 300mg dose of tenofovir.

Outcome measures

Outcome measures
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment
Semen Clearance (CL) of Tenofovir Diphosphate	21 fmol/10x6 cells Interval 5.7 to 88.0	21 fmol/10x6 cells Interval 4.2 to 91.0	35 fmol/10x6 cells Interval 24.0 to 78.0

PRIMARY outcome

Timeframe: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose

Population: Semen (SMC) Steady State Concentrations (Css,ave) of Emtricitabine Triphosphate

Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of emtricitabine triphosphate, an intracellular metabolite of emtricitabine, from seminal mononuclear cells, following a 200mg dose of emtricitabine.

Outcome measures

Outcome measures
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment
Semen Clearance (CL) of Emtricitabine Triphosphate	59 fmol/10 E6 cells Interval 22.0 to 119.0	90 fmol/10 E6 cells Interval 34.0 to 193.0	179 fmol/10 E6 cells Interval 108.0 to 395.0

PRIMARY outcome

Timeframe: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose

Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of tenofovir diphosphate, an intracellular metabolite of tenofovir, from peripheral blood mononuclear cells, following a 300mg dose of tenofovir.

Outcome measures

Outcome measures
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment
Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Tenofovir Diphosphate	174 fmol/10 E6 cells Interval 115.0 to 239.0	119 fmol/10 E6 cells Interval 76.0 to 174.0	935 fmol/10 E6 cells Interval 684.0 to 2024.0

PRIMARY outcome

Timeframe: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose

Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of emtricitabine triphosphate, an intracellular metabolite of emtricitabine, from peripheral blood mononuclear cells, following a 200mg dose of emtricitabine.

Outcome measures

Outcome measures
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment
Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Emtricitabine Triphosphate	6038 fmol/10 E6 cells Interval 4465.0 to 10088.0	6135 fmol/10 E6 cells Interval 3889.0 to 8303.0	8242 fmol/10 E6 cells Interval 5602.0 to 13480.0

SECONDARY outcome

Timeframe: Average concentration in a 24 hour dosing interval

dATP concentrations in seminal mononuclear cells will be measured and compared to tenofovir diphosphate concentrations, using a ratio, and summarized descriptively for each subject, as well as across subjects. As the six seminal cell samples collected per man were pooled for analysis due to low cell recovery, a single ratio value per participant was calculated and summarized by study arm.

Outcome measures

Outcome measures
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment
Tenofovir Diphosphate (TFVdp)/Deoxyadenosine Triphosphate (dATP) Ratio in Seminal Mononuclear Cells	0.99 TFVdp:dATP ratio Interval 0.43 to 1.54	0.66 TFVdp:dATP ratio Interval 0.22 to 1.21	1.10 TFVdp:dATP ratio Interval 0.42 to 1.7

SECONDARY outcome

Timeframe: Average concentration in a 24 hour dosing interval

dCTP concentrations in seminal mononuclear cells will be measured and compared to emtricitabine triphosphate concentrations, using a ratio, and summarized descriptively for each subject, as well as across subjects. As the six seminal cell samples collected per man were pooled for analysis due to low cell recovery, a single ratio value per participant was calculated and summarized by study arm.

Outcome measures

Outcome measures
Measure	HIV Positive TDF/FTC n=8 Participants 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 Participants 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 Participants 8 HIV positive men taking TAF as treatment
Emtricitabine Triphosphate (FTCtp)/Deoxyadenosine Triphosphate (dCTP) Ratio in Seminal Mononuclear Cells	0.52 FTCtp:dCTP ratio Interval 0.38 to 1.14	0.96 FTCtp:dCTP ratio Interval 0.39 to 1.85	3.81 FTCtp:dCTP ratio Interval 2.3 to 3.98

Adverse Events

HIV Positive TDF/FTC

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

HIV Negative

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

HIV Positive TAF

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	HIV Positive TDF/FTC n=8 participants at risk 8 HIV positive men taking TDF/FTC as treatment	HIV Negative n=8 participants at risk 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis	HIV Positive TAF n=8 participants at risk 8 HIV positive men taking TAF as treatment
Respiratory, thoracic and mediastinal disorders Viral Pharyngitis	0.00% 0/8 • Adverse events were collected from the time of informed consent, until end of study enrollment. does not differ	12.5% 1/8 • Number of events 1 • Adverse events were collected from the time of informed consent, until end of study enrollment. does not differ	0.00% 0/8 • Adverse events were collected from the time of informed consent, until end of study enrollment. does not differ
Skin and subcutaneous tissue disorders Penile skin irritation	0.00% 0/8 • Adverse events were collected from the time of informed consent, until end of study enrollment. does not differ	0.00% 0/8 • Adverse events were collected from the time of informed consent, until end of study enrollment. does not differ	12.5% 1/8 • Number of events 1 • Adverse events were collected from the time of informed consent, until end of study enrollment. does not differ

Additional Information

Julie B. Dumond, PharmD, MS, BCPS, AAHIVP

University of North Carolina at Chapel Hill

Phone: 919-966-5017

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place