Trial Outcomes & Findings for Bioequivalence of Tenofovir and Emtricitabine Following Overencapsulation (NCT NCT02968576)

NCT ID: NCT02968576

Last Updated: 2020-03-06

Results Overview

Tenofovir and emtricitabine concentration max (Cmax) following FTC/TDF in the overencapsulated versus non-encapsulated form. Drug concentrations will be assayed with validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methodology.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 25 participants
• Primary outcome timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
• Results posted on: 2020-03-06

Participant Flow

IRB approval was obtained for 48 subjects to allow for screen failures, withdrawals, lost to follow up, etc.

Participant milestones

Measure	Truvada First, Then Coencapsulated PSS-Truvada Single dose of unencapsulated Truvada (Tenofovir disoproxil fumarate 300mg/Emtricitabine 200mg), 14-day washout followed by single dose of Truvada coencapsulated with the Proteus Sensor System (PSS) (device).	Coencapsulated PSS-Truvada First, Then Truvada Single dose of Truvada (Tenofovir disoproxil fumarate 300mg/Emtricitabine 200mg) coencapsulated with the Proteus Sensor System (PSS) (device), 14-day washout followed by single dose of unencapsulated Truvada.
Overall Study STARTED	11	14
Overall Study COMPLETED	11	13
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Truvada First, Then Coencapsulated PSS-Truvada Single dose of unencapsulated Truvada (Tenofovir disoproxil fumarate 300mg/Emtricitabine 200mg), 14-day washout followed by single dose of Truvada coencapsulated with the Proteus Sensor System (PSS) (device).	Coencapsulated PSS-Truvada First, Then Truvada Single dose of Truvada (Tenofovir disoproxil fumarate 300mg/Emtricitabine 200mg) coencapsulated with the Proteus Sensor System (PSS) (device), 14-day washout followed by single dose of unencapsulated Truvada.
Overall Study Pregnancy	0	1

Baseline Characteristics

Bioequivalence of Tenofovir and Emtricitabine Following Overencapsulation

Baseline characteristics by cohort

Measure	All Participants n=25 Participants Single dose of unencapsulated and coencapsulated TDF/FTC. A 14-day washout separated each dosing.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic	3 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · African American	3 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Caucasian	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose

Population: All subjects who completed the study: single dose of unencapsulated and coencapsulated TDF/FTC. A 14-day washout separated each dosing.

Tenofovir and emtricitabine concentration max (Cmax) following FTC/TDF in the overencapsulated versus non-encapsulated form. Drug concentrations will be assayed with validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methodology.

Outcome measures

Measure	All Participants n=477 PK timepoint samples Single dose of unencapsulated and coencapsulated TDF/FTC. A 14-day washout separated each dosing.
Peak Plasma Concentration (Cmax) TFV Cmax-unencapsulated	222 ng/mL Geometric Coefficient of Variation 37
Peak Plasma Concentration (Cmax) TFV Cmax-coencapsulated	229 ng/mL Geometric Coefficient of Variation 32
Peak Plasma Concentration (Cmax) FTC Cmax-unencapsulated	1567 ng/mL Geometric Coefficient of Variation 33
Peak Plasma Concentration (Cmax) FTC Cmax-coencapsulated	1684 ng/mL Geometric Coefficient of Variation 29

PRIMARY outcome

Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose

Population: All subjects who completed the study: single dose of unencapsulated and coencapsulated TDF/FTC. A 14-day washout separated each dosing.

Tenofovir and emtricitabine area under the concentration-time curve (AUC) following FTC/TDF in the overencapsulated versus non-encapsulated form. Drug concentrations will be assayed with validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methodology.

Outcome measures

Measure	All Participants n=477 PK timepoint samples Single dose of unencapsulated and coencapsulated TDF/FTC. A 14-day washout separated each dosing.
Area Under the Concentration-time Curve (AUC) TFV AUC-unencapsulated	1978 ng*h/mL Geometric Coefficient of Variation 27
Area Under the Concentration-time Curve (AUC) TFV AUC-coencapsulated	2042 ng*h/mL Geometric Coefficient of Variation 26
Area Under the Concentration-time Curve (AUC) FTC AUC-unencapsulated	9342 ng*h/mL Geometric Coefficient of Variation 23
Area Under the Concentration-time Curve (AUC) FTC AUC-coencapsulated	9512 ng*h/mL Geometric Coefficient of Variation 20

Adverse Events

All Subjects

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	All Subjects n=25 participants at risk Overall, the study showed an unremarkable and expected AE profile. At study initiation Truvada was FDA approved thus, the AE profile was already established. This study was not designed to collect new safety data or to update the established AE/Safety profiles for Truvada. Therefore AE data was combined for all dosing regimens since AEs reported per arm/group are not meaningful for research or clinical applications.
Gastrointestinal disorders Nausea	12.0% 3/25 • Number of events 3 • Time of consenting to study exit, Max. 54 days AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available on the DAIDS RSC Web site: http://rsc.tech-res.com/safetyandpharmacovigilance/
Gastrointestinal disorders Vomitting	4.0% 1/25 • Number of events 1 • Time of consenting to study exit, Max. 54 days AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available on the DAIDS RSC Web site: http://rsc.tech-res.com/safetyandpharmacovigilance/
General disorders Headache	4.0% 1/25 • Number of events 1 • Time of consenting to study exit, Max. 54 days AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available on the DAIDS RSC Web site: http://rsc.tech-res.com/safetyandpharmacovigilance/
General disorders Common Cold	28.0% 7/25 • Number of events 7 • Time of consenting to study exit, Max. 54 days AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available on the DAIDS RSC Web site: http://rsc.tech-res.com/safetyandpharmacovigilance/
Respiratory, thoracic and mediastinal disorders Respiratory Infection	4.0% 1/25 • Number of events 1 • Time of consenting to study exit, Max. 54 days AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available on the DAIDS RSC Web site: http://rsc.tech-res.com/safetyandpharmacovigilance/
General disorders Facial Swelling	4.0% 1/25 • Number of events 1 • Time of consenting to study exit, Max. 54 days AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available on the DAIDS RSC Web site: http://rsc.tech-res.com/safetyandpharmacovigilance/

Additional Information

Dr. Peter Anderson

University of Colorado | Skaggs School of Pharmacy and Pharmaceutical Sciences

Phone: 3037246128

Email: peter.anderson@ucdenver.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place