Trial Outcomes & Findings for Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003) (NCT NCT01930058)
NCT ID: NCT01930058
Last Updated: 2018-10-25
Results Overview
The mean change (log10) in HCV ribonucleic acid (RNA) from baseline to Day 7 was determined for each panel of participants.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
9 participants
Primary outcome timeframe
Baseline and Day 7
Results posted on
2018-10-25
Participant Flow
Participant milestones
| Measure |
Panel A: HCV GT3 MK-8876 150 mg
Participants infected with HCV GT3 received 150 mg MK-8876 once daily (q.d.) by mouth for 7 days.
|
Panel B: HCV GT3 MK-8876 800 mg
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Panel E: HCV GT1a MK-8876 800 mg
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Pharmacokinetics, and Pharmacodynamics of MK-8876 in Participants With Hepatitis C Infection (MK-8876-003)
Baseline characteristics by cohort
| Measure |
Panel A: HCV GT3 MK-8876 150 mg
n=3 Participants
Participants infected with HCV GT3 received 150 mg MK-8876 q.d. by mouth for 7 days.
|
Panel B: HCV GT3 MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Panel E: HCV GT1a MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
32 Years
STANDARD_DEVIATION 2.6 • n=5 Participants
|
45 Years
STANDARD_DEVIATION 12.5 • n=7 Participants
|
49.7 Years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
42.2 Years
STANDARD_DEVIATION 10.8 • 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
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 7Population: All participants in Panels A, B, and E are included in the analysis.
The mean change (log10) in HCV ribonucleic acid (RNA) from baseline to Day 7 was determined for each panel of participants.
Outcome measures
| Measure |
Panel A: HCV GT3 MK-8876 150 mg
n=3 Participants
Participants infected with HCV GT3 received 150 mg MK-8876 q.d. by mouth for 7 days.
|
Panel B: HCV GT3 MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Panel E: HCV GT1a MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
|
|---|---|---|---|
|
Mean Change From Baseline in HCV Viral Load
|
-0.42 Log10 change
Standard Error 0.12
|
-1.88 Log10 change
Standard Error 0.5
|
-3.39 Log10 change
Standard Error 0.27
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7Population: All participants in Panels A, B, and E are included in the analysis.
AUC0-24hr is a measure of the mean concentration of drug in plasma after dosing to 24 hr post-dose. Plasma AUC0-24hr was calculated on Day 1 and Day 7 of MK-8876 dosing.
Outcome measures
| Measure |
Panel A: HCV GT3 MK-8876 150 mg
n=3 Participants
Participants infected with HCV GT3 received 150 mg MK-8876 q.d. by mouth for 7 days.
|
Panel B: HCV GT3 MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Panel E: HCV GT1a MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876
Day 1
|
1.9 µM*hr
Geometric Coefficient of Variation 88.6
|
4.83 µM*hr
Geometric Coefficient of Variation 26.1
|
10.7 µM*hr
Geometric Coefficient of Variation 16.5
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (hr) Post-dose (AUC0-24 hr) of MK-8876
Day 7
|
5.23 µM*hr
Geometric Coefficient of Variation 113.7
|
23.1 µM*hr
Geometric Coefficient of Variation 13.2
|
23.1 µM*hr
Geometric Coefficient of Variation 22.0
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7Population: All participants in Panels A, B, and E are included in the analysis.
Cmax is a measure of the maximum plasma concentration of drug post-dose. Plasma Cmax was determined on Day 1 and Day 7 of MK-8876 dosing.
Outcome measures
| Measure |
Panel A: HCV GT3 MK-8876 150 mg
n=3 Participants
Participants infected with HCV GT3 received 150 mg MK-8876 q.d. by mouth for 7 days.
|
Panel B: HCV GT3 MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Panel E: HCV GT1a MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of MK-8876
Day 1
|
177 nM
Geometric Coefficient of Variation 69.7
|
373 nM
Geometric Coefficient of Variation 29.7
|
773 nM
Geometric Coefficient of Variation 26.1
|
|
Maximum Plasma Concentration (Cmax) of MK-8876
Day 7
|
375 nM
Geometric Coefficient of Variation 70.7
|
1310 nM
Geometric Coefficient of Variation 12.3
|
1380 nM
Geometric Coefficient of Variation 22.9
|
SECONDARY outcome
Timeframe: 24 hours post-dose on Days 1 and 7Population: All participants in Panels A, B, and E are included in the analysis.
C24hr is a measure of the plasma drug concentration 24 hours post-dose (i.e., trough concentration). Plasma C24hr was determined on Day 1 and Day 7 of MK-8876 dosing.
Outcome measures
| Measure |
Panel A: HCV GT3 MK-8876 150 mg
n=3 Participants
Participants infected with HCV GT3 received 150 mg MK-8876 q.d. by mouth for 7 days.
|
Panel B: HCV GT3 MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Panel E: HCV GT1a MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
|
|---|---|---|---|
|
Trough Plasma Concentration (C24hr) of MK-8876
Day 1
|
59.1 nM
Geometric Coefficient of Variation 99.5
|
189 nM
Geometric Coefficient of Variation 17.1
|
370 nM
Geometric Coefficient of Variation 18.2
|
|
Trough Plasma Concentration (C24hr) of MK-8876
Day 7
|
173 nM
Geometric Coefficient of Variation 140.7
|
907 nM
Geometric Coefficient of Variation 17
|
869 nM
Geometric Coefficient of Variation 21.4
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7Population: All participants in Panels A, B, and E are included in the analysis.
Tmax is a measure of time required to reach the maximum plasma drug concentration post-dose. Plasma Tmax was calculated on Day 1 and Day 7 of MK-8876 dosing.
Outcome measures
| Measure |
Panel A: HCV GT3 MK-8876 150 mg
n=3 Participants
Participants infected with HCV GT3 received 150 mg MK-8876 q.d. by mouth for 7 days.
|
Panel B: HCV GT3 MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Panel E: HCV GT1a MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
|
|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) of MK-8876
Day 7
|
4 Hours
Interval 4.0 to 6.0
|
4 Hours
Interval 2.0 to 6.0
|
4 Hours
Interval 2.0 to 4.0
|
|
Time to Maximum Plasma Concentration (Tmax) of MK-8876
Day 1
|
4 Hours
Interval 4.0 to 6.0
|
6 Hours
Interval 4.0 to 6.0
|
4 Hours
Interval 4.0 to 8.0
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Day 7Population: All participants in Panels A, B, and E are included in the analysis.
t½ is the time required for the maximum plasma drug concentration to reduce by 50% post-dose. Plasma t½ was determined on Day 7 of MK-8876 dosing.
Outcome measures
| Measure |
Panel A: HCV GT3 MK-8876 150 mg
n=3 Participants
Participants infected with HCV GT3 received 150 mg MK-8876 q.d. by mouth for 7 days.
|
Panel B: HCV GT3 MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT3 received 800 mg MK-8876 q.d. by mouth for 7 days.
|
Panel E: HCV GT1a MK-8876 800 mg
n=3 Participants
Participants infected with HCV GT1a received 800 mg MK-8876 q.d. by mouth for 7 days.
|
|---|---|---|---|
|
Apparent Terminal Plasma Half-life (t½) of MK-8876
|
77.1 Hours
Geometric Coefficient of Variation 20.5
|
140 Hours
Geometric Coefficient of Variation 24.2
|
62.5 Hours
Geometric Coefficient of Variation 66.1
|
Adverse Events
MK-8876 150 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
MK-8876 800 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
MK-8876 150 mg
n=3 participants at risk
All HCV GT3 participants treated with MK-8876 150 mg are included.
|
MK-8876 800 mg
n=6 participants at risk
All HCV GT1a and GT3 participants treated with MK-8876 800 mg are included.
|
|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/3 • Up to Day 21
All AE data for GT1a and GT3 participants treated with MK-8876 800 mg were combined.
|
33.3%
2/6 • Number of events 2 • Up to Day 21
All AE data for GT1a and GT3 participants treated with MK-8876 800 mg were combined.
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
1/3 • Number of events 1 • Up to Day 21
All AE data for GT1a and GT3 participants treated with MK-8876 800 mg were combined.
|
0.00%
0/6 • Up to Day 21
All AE data for GT1a and GT3 participants treated with MK-8876 800 mg were combined.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.
- Publication restrictions are in place
Restriction type: OTHER