NCT02985996

Body Compartment PK for New HIV Pre-exposure Prophylaxis Modalities

Completed Phase 1 Results posted Last updated 17 September 2019

What this trial tests

Phase 1 trial testing Truvada in HIV Infections in 48 participants. Completed in 29 November 2017.

Timeline

6 February 2017

Primary endpoint
29 November 2017

29 November 2017

Quick facts

Lead sponsor	Emory University
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	48
Start date	6 February 2017
Primary completion	29 November 2017
Estimated completion	29 November 2017
Sites	1 location across United States

Drugs / interventions tested

• Truvada — full drug profile →
• Genvoya — full drug profile →

Conditions studied

• HIV Infections — all drugs for HIV Infections →

Sponsor

Emory University

Who can join

Adults 18 to 49, male only, with HIV Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Changes in Intracellular Emtricitabine Triphosphate (FTC-TP) Primary · Baseline, Visit 4 (Up to ten days post drug)

Intracellular emtricitabine triphosphate (FTC-TP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	3380	2091 – 4320
Phase II/Truvada	2580	1531 – 5340
Phase III/Genvoya	6470	3030 – 15,380
Phase III/Truvada	7660	3170 – 10,470

Changes in Intracellular Tenofovir Diphosphate (TFV-DP) Primary · Baseline, Visit 4 (Up to ten days post drug)

Intracellular tenofovir diphosphate (TFV-DP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	213	111 – 323
Phase II/Truvada	28	0 – 32
Phase III/Genvoya	453	138 – 897
Phase III/Truvada	80	0 – 156

Change in Plasma Emtricitabine (FTC) Concentration Secondary · Baseline, Visit 4 (Up to ten days post drug)

Plasma emtricitabine (FTC) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	30	12 – 46
Phase II/Truvada	34	20 – 206
Phase III/Genvoya	152	31 – 613
Phase III/Truvada	280	66 – 518

Change in Plasma Tenofovir Disoproxil Fumarate (TDF) Concentration Secondary · Baseline, Visit 4 (Up to ten days post drug)

Plasma tenofovir disoproxil fumarate (TDF) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Short Course	0	0 – 0
Phase III/Steady State	28	20 – 59
Phase III/Genvoya	0	0 – 0
Phase III/Truvada	59	38 – 89

Change in Plasma Elvitegravir (EVG) Concentration Secondary · Baseline, Visit 4 (Up to ten days post drug)

Plasma elvitegravir (EVG) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	102	0 – 295
Phase II/Truvada	0	0 – 0
Phase III/Genvoya	384	99 – 705
Phase III/Truvada	0	0 – 0

Change in Rectal Emtricitabine (FTC) Concentration Secondary · Baseline, Visit 4 (Up to ten days post drug)

Emtricitabine (FTC) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	288	0 – 42,450
Phase II/Truvada	419	64 – 6935
Phase III/Genvoya	371	0 – 3830
Phase III/Truvada	109	0 – 3900

Change in Rectal Tenofovir Disoproxil Fumarate (TDF) Concentration Secondary · Baseline, Visit 4 (Up to ten days post drug)

Tenofovir disoproxil fumarate (TDF), concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	58	0 – 1195
Phase II/Truvada	45	0 – 263
Phase III/Genvoya	533	0 – 18,400
Phase III/Truvada	1325	0 – 6145

Change in Rectal Elvitegravir (EVG) Concentration Secondary · Baseline, Visit 4 (Up to ten days post drug)

Elvitegravir (EVG) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	405	55 – 7975
Phase II/Truvada	0	0 – 0
Phase III/Genvoya	219	0 – 54,100
Phase III/Truvada	0	0 – 0

Change in Intracellular Emtricitabine (FTC) Concentration in Rectal Tissue Secondary · Baseline, Visit 4 (Up to ten days post drug)

Tissue emtricitabine (FTC) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	0	0 – 11
Phase II/Truvada	0	0 – 51
Phase III/Genvoya	27	0 – 79
Phase III/Truvada	41	0 – 110

Change in Intracellular Tenofovir (TFV) Concentration in Rectal Tissue Secondary · Baseline, Visit 4 (Up to ten days post drug)

Intracellular tenofovir (TFV) Concentration in Rectal Tissue is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	17	0 – 65
Phase II/Truvada	11	0 – 74
Phase III/Genvoya	0	0 – 102
Phase III/Truvada	0	0 – 17

Change in Elvitegravir (EVG) Concentration in Rectal Tissue Secondary · Baseline, Visit 4 (Up to ten days post drug)

Tissue elvitegravir (EVG) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Genvoya	2.7	1.2 – 9.8
Phase II/Truvada	0	0 – 0
Phase III/Genvoya	6.8	4.5 – 11.1
Phase III/Truvada	0	0 – 0

Change in Emtricitabine (FTC) Concentration in Penile Secretions Secondary · Baseline, Visit 4 (Up to ten days post drug)

Emtricitabine (FTC) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as "Below the Limit of Quantification" (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Group	Value	95% CI
Phase I/Pre-Drug	0	0 – 0
Phase II/Short Course	32	0 – 77
Phase III/Steady State	30	0 – 406
Phase III/Genvoya	175	0 – 1775
Phase III/Truvada	54	0 – 9685

Sponsor's own description

The purpose of this study is to determine the ability of new anti-HIV agents to penetrate different body compartments in HIV negative men who have sex with men and transgender women. These new agents might be considered for pre-exposure prophylaxis regimens in the future. This study will include 90 healthy, HIV-negative men who have sex with men and transgender women who are not taking hormones aged 18-49 years. Participant must be willing to participate in 1 of the 3 study phases, be willing to take Truvada® (PrEP) or Genvoya®, and willing to undergo blood draws, urethral swabs, and rectal biopsy procedures.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Single oral dose for HIV pre or post-exposure prophylaxis: user desirability and biological efficacy in macaques.
   Massud I, Ruone S, Zlotorzynska M, Haaland R, et al · · 2020 · cited 19× · PMID 32707451 · DOI 10.1016/j.ebiom.2020.102894
2. Brief Report: Urine Emtricitabine and Tenofovir Concentrations Provide Markers of Recent Antiretroviral Drug Exposure Among HIV-Negative Men Who Have Sex With Men.
   Haaland RE, Martin A, Livermont T, Fountain J, et al · · 2019 · cited 12× · PMID 31335590 · DOI 10.1097/qai.0000000000002133