Trial Outcomes & Findings for Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/HCV Seronegative Volunteers (NCT NCT02404805)
NCT ID: NCT02404805
Last Updated: 2021-03-17
Results Overview
Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
25 participants
Primary outcome timeframe
Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7
Results posted on
2021-03-17
Participant Flow
Participant milestones
| Measure |
Sequence 1a
Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 1b
Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 2a
Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 2b
Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 3a
Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 3b
Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
3
|
5
|
5
|
3
|
4
|
|
Overall Study
COMPLETED
|
4
|
3
|
5
|
5
|
3
|
4
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1a
Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 1b
Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 2a
Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 2b
Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 3a
Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 3b
Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/HCV Seronegative Volunteers
Baseline characteristics by cohort
| Measure |
Sequence 1a
n=5 Participants
Sequence 1,2,3: simeprevir only, then dolutegravir only, then both simeprevir and dolutegravir.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 1b
n=3 Participants
Sequence 1,3,2: simeprevir only, then both simeprevir and dolutegravir, then dolutegravir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 2a
n=5 Participants
Sequence 2,1,3: dolutegravir only, then simeprevir only, then both simeprevir and dolutegravir.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 2b
n=5 Participants
Sequence 2,3,1: dolutegravir only, then both simeprevir and dolutegravir, then simeprevir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 3a
n=3 Participants
Sequence 3,1,2: both simeprevir and dolutegravir, then simeprevir only, then dolutegravir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Sequence 3b
n=4 Participants
Sequence 3,2,1: Both simeprevir and dolutegravir, then dolutegravir only, then simeprevir only.
dolutegravir: dolutegravir tablets 50mg, once daily x 7 days.
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Total
n=25 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
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
25 Participants
n=115 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
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Continuous
|
30.8 years
n=5 Participants
|
34.3 years
n=7 Participants
|
36.4 years
n=5 Participants
|
35.6 years
n=4 Participants
|
35.7 years
n=21 Participants
|
33.8 years
n=10 Participants
|
34.3 years
n=115 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
16 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
ETHNICITY · CAUCASIAN
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
22 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
ETHNICITY · HISPANIC
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
5 participants
n=4 Participants
|
3 participants
n=21 Participants
|
4 participants
n=10 Participants
|
25 participants
n=115 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7Population: Only arms that included Simeprevir administration are included.
Determine simeprevir area-under-the concentration time curve (AUC) when administered alone and when being co-administered with Dolutegravier.
Outcome measures
| Measure |
Simeprevir Administered Alone
n=24 Participants
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Simeprevir and Dolutegravier Co-administered
n=24 Participants
Dolutegravir and simeprevir together:
dolutegravir tablets 50mg, once daily and simeprevir tablets 150mg, once daily x 7 days.
|
|---|---|---|
|
Simeprevir AUC Pharmacokinetics
|
30946 ng*h/mL
Geometric Coefficient of Variation 80
|
30333 ng*h/mL
Geometric Coefficient of Variation 82
|
PRIMARY outcome
Timeframe: Pre-dose and, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose on day 7Population: Only arms that included Dolutegravir administration are included.
Determine Dolutegravir area-under-the concentration time curve (AUC) when administered alone and when co-administered with simeprevir.
Outcome measures
| Measure |
Simeprevir Administered Alone
n=24 Participants
simeprevir: simeprevir tablets 150mg, once daily x 7 days.
|
Simeprevir and Dolutegravier Co-administered
n=24 Participants
Dolutegravir and simeprevir together:
dolutegravir tablets 50mg, once daily and simeprevir tablets 150mg, once daily x 7 days.
|
|---|---|---|
|
Dolutegravir AUC Pharmacokinetics
|
68186 ng*h/mL
Geometric Coefficient of Variation 30
|
78433 ng*h/mL
Geometric Coefficient of Variation 24
|
Adverse Events
Simeprevir Only
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Dolutegravir Only
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Dolutegravir and Simeprevir Co-administered:
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Simeprevir Only
n=25 participants at risk
Simeprevir tablets 150mg, once daily x 7 days.
|
Dolutegravir Only
n=24 participants at risk
Dolutegravir tablets 50mg, once daily x 7 days.
|
Dolutegravir and Simeprevir Co-administered:
n=24 participants at risk
Dolutegravir and simeprevir co-administered:
dolutegravir tablets 50mg, once daily, and simeprevir tablets 150mg, once daily, x 7 days
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
8.0%
2/25 • Number of events 2 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
12.5%
3/24 • Number of events 3 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
12.5%
3/24 • Number of events 3 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
|
Gastrointestinal disorders
Gastrointestinal issues (stomach pain, gas, vomiting, nausea, diarrhea)
|
8.0%
2/25 • Number of events 2 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
16.7%
4/24 • Number of events 4 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
12.5%
3/24 • Number of events 3 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
|
General disorders
Fatigue
|
0.00%
0/25 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
0.00%
0/24 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
8.3%
2/24 • Number of events 2 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
0.00%
0/25 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
0.00%
0/24 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
8.3%
2/24 • Number of events 2 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
|
General disorders
Abnormal Labs
|
4.0%
1/25 • Number of events 1 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
20.8%
5/24 • Number of events 7 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
29.2%
7/24 • Number of events 7 • Time of consenting to study exit (Phone follow up 7 days after final intensive PK visit, max 3 months)
AEs were graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November, 2014. Available: http://rsc.tech-res.com/safetyandpharmacovigilance/.
|
Additional Information
Dr. Jennifer Kiser
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
Phone: (303) 724-6131
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place