Trial Outcomes & Findings for Pre-Exposure Prophylaxis (PrEP) Adherence Monitoring Using Dried Blood Spots (NCT NCT02022657)
NCT ID: NCT02022657
Last Updated: 2019-04-30
Results Overview
TFV-DP concentrations in DBS respective to dosing regimens of 33%, 67%, 100% of daily dosing.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
52 participants
Primary outcome timeframe
Assessed every 2 weeks during the dosing periods and at steady-state, week 12 for the first dosing period and week 36 for the second dosing period.
Results posted on
2019-04-30
Participant Flow
52 subjects from 2 sites were analyzed-- CU enrolled only 34.
Participant milestones
| Measure |
100% First, Then 67%
100% dosing: Dose every day for \~12 weeks 67% holiday dosing regimen: 2 weeks on medication, 1 week off, repeat for \~ 12 weeks 67% intermittent dosing regimen: 2 days on medication, 1 day off, repeat for \~ 12 weeks
67% Intermittent and 67% Holiday dosing combined for analysis.
|
100% First, Then 33%
100% dosing regimen: dosing every day for \~12 weeks 33% holiday dosing regimen: 1 week on medication, 2 weeks off, repeat for \~ 12 weeks 33% intermittent dosing regimen:1 day on medication, 2 days off, repeat for \~ 12 weeks
33% Intermittent and 33% Holiday dosing combined for analysis.
|
67% First, Then 100%
67% holiday dosing regimen: 2 weeks on medication, 1 week off, repeat for \~ 12 weeks 67% intermittent dosing regimen: 2 days on medication, 1 day off, repeat for \~ 12 weeks 100% dosing regimen: dosing every day, repeat for \~12 weeks
67% Intermittent and 67% Holiday dosing combined for analysis.
|
67% First, Then 33%
67% holiday dosing regimen: 2 weeks on medication, 1 week off, repeat for \~ 12 weeks 67% intermittent dosing regimen: 2 days on medication, 1 day off, repeat for \~ 12 weeks 33% holiday dosing regimen: 1 week on medication, 2 weeks off, repeat for \~ 12 weeks 33% intermittent dosing regimen:1 day on medication, 2 days off, repeat for \~ 12 weeks
67% Intermittent and 67% Holiday dosing combined for analysis. 33% Intermittent and 33% Holiday dosing combined for analysis.
|
33% First, Then 100%
33% holiday dosing regimen: 1 week on medication, 2 weeks off, repeat for \~ 12 weeks 33% intermittent dosing regimen:1 day on medication, 2 days off, repeat for \~ 12 weeks 100% dosing: Dose every day for \~12 weeks
33% Intermittent and 33% Holiday dosing combined for analysis.
|
33% First, Then 67%
33% holiday dosing regimen: 1 week on medication, 2 weeks off, repeat for \~ 12 weeks 33% intermittent dosing regimen:1 day on medication, 2 days off, repeat for \~ 12 weeks 67% holiday dosing regimen: 2 weeks on medication, 1 week off, repeat for \~ 12 weeks 67% intermittent dosing regimen: 2 days on medication, 1 day off, repeat for \~ 12 weeks
33% Intermittent and 33% Holiday dosing combined for analysis. 67% Intermittent and 67% Holiday dosing combined for analysis.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
8
|
9
|
8
|
8
|
9
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
1
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
100% First, Then 67%
100% dosing: Dose every day for \~12 weeks 67% holiday dosing regimen: 2 weeks on medication, 1 week off, repeat for \~ 12 weeks 67% intermittent dosing regimen: 2 days on medication, 1 day off, repeat for \~ 12 weeks
67% Intermittent and 67% Holiday dosing combined for analysis.
|
100% First, Then 33%
100% dosing regimen: dosing every day for \~12 weeks 33% holiday dosing regimen: 1 week on medication, 2 weeks off, repeat for \~ 12 weeks 33% intermittent dosing regimen:1 day on medication, 2 days off, repeat for \~ 12 weeks
33% Intermittent and 33% Holiday dosing combined for analysis.
|
67% First, Then 100%
67% holiday dosing regimen: 2 weeks on medication, 1 week off, repeat for \~ 12 weeks 67% intermittent dosing regimen: 2 days on medication, 1 day off, repeat for \~ 12 weeks 100% dosing regimen: dosing every day, repeat for \~12 weeks
67% Intermittent and 67% Holiday dosing combined for analysis.
|
67% First, Then 33%
67% holiday dosing regimen: 2 weeks on medication, 1 week off, repeat for \~ 12 weeks 67% intermittent dosing regimen: 2 days on medication, 1 day off, repeat for \~ 12 weeks 33% holiday dosing regimen: 1 week on medication, 2 weeks off, repeat for \~ 12 weeks 33% intermittent dosing regimen:1 day on medication, 2 days off, repeat for \~ 12 weeks
67% Intermittent and 67% Holiday dosing combined for analysis. 33% Intermittent and 33% Holiday dosing combined for analysis.
|
33% First, Then 100%
33% holiday dosing regimen: 1 week on medication, 2 weeks off, repeat for \~ 12 weeks 33% intermittent dosing regimen:1 day on medication, 2 days off, repeat for \~ 12 weeks 100% dosing: Dose every day for \~12 weeks
33% Intermittent and 33% Holiday dosing combined for analysis.
|
33% First, Then 67%
33% holiday dosing regimen: 1 week on medication, 2 weeks off, repeat for \~ 12 weeks 33% intermittent dosing regimen:1 day on medication, 2 days off, repeat for \~ 12 weeks 67% holiday dosing regimen: 2 weeks on medication, 1 week off, repeat for \~ 12 weeks 67% intermittent dosing regimen: 2 days on medication, 1 day off, repeat for \~ 12 weeks
33% Intermittent and 33% Holiday dosing combined for analysis. 67% Intermittent and 67% Holiday dosing combined for analysis.
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Pre-Exposure Prophylaxis (PrEP) Adherence Monitoring Using Dried Blood Spots
Baseline characteristics by cohort
| Measure |
All Dosing Regimens
n=48 Participants
Baseline characteristics for all 48 subjects included in analysis. Baseline characteristics not stratified based on dosing regimen.
|
|---|---|
|
Age, Continuous
|
29 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
26 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
8 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Assessed every 2 weeks during the dosing periods and at steady-state, week 12 for the first dosing period and week 36 for the second dosing period.Population: The total number of participants was 48. Each participant was randomized to 2 of 3 dosing regimens for a total of 32 participants each, however 2 participants completed only the first regimen.
TFV-DP concentrations in DBS respective to dosing regimens of 33%, 67%, 100% of daily dosing.
Outcome measures
| Measure |
DOT-DBS Dosing 33%
n=30 Participants
33%
|
DOT-DBS Dosing 67%
n=32 Participants
67%
|
DOT-DBS Dosing 100%
n=32 Participants
|
|---|---|---|---|
|
Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada
|
530 fmol/punch
Standard Deviation 159
|
997 fmol/punch
Standard Deviation 267
|
1605 fmol/punch
Standard Deviation 405
|
Adverse Events
All Dosing Regimens
Serious events: 1 serious events
Other events: 48 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Dosing Regimens
n=48 participants at risk
Overall, the study showed an unremarkable and expected AE profile. At study initiation Truvada was FDA approved for daily dosing (100% daily dosing). Thus, the AE profile was already established for 100% dosing and AE rates in the lower doses (33% and 67%) would not exceed the established rate for daily dosing (100%). 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.
|
|---|---|
|
Psychiatric disorders
Anxiety
|
2.1%
1/48 • Number of events 1 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.1%
1/48 • Number of events 1 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
Other adverse events
| Measure |
All Dosing Regimens
n=48 participants at risk
Overall, the study showed an unremarkable and expected AE profile. At study initiation Truvada was FDA approved for daily dosing (100% daily dosing). Thus, the AE profile was already established for 100% dosing and AE rates in the lower doses (33% and 67%) would not exceed the established rate for daily dosing (100%). 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.
|
|---|---|
|
General disorders
Cold Symptoms
|
85.4%
41/48 • Number of events 83 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
Gastrointestinal disorders
Abdominal Pain
|
29.2%
14/48 • Number of events 17 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
Gastrointestinal disorders
Diarrhea
|
14.6%
7/48 • Number of events 12 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
General disorders
Headache
|
14.6%
7/48 • Number of events 10 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
Gastrointestinal disorders
Nausea
|
31.2%
15/48 • Number of events 24 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
Gastrointestinal disorders
Vomitting
|
8.3%
4/48 • Number of events 7 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
General disorders
Fatigue
|
29.2%
14/48 • Number of events 16 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
General disorders
Loss of Appetite
|
6.2%
3/48 • Number of events 5 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
|
General disorders
Abnormal Labs
|
66.7%
32/48 • Number of events 88 • Time of consenting to study exit (Week 36 or earlier), Max 10 months.
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V1.0 Aug 2009 (US Dept HHS, NIH, NIAID) Available from: http://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf Arms were combined as Truvada was FDA approved for daily use (100% dosing) at the time of study initiation- no arm was considered to be more at risk for AEs than another.
|
Additional Information
Dr. Peter Anderson
Skaggs School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora
Phone: 3037246821
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place