Trial Outcomes & Findings for The Influence of Hepatic Insufficiency on the Pharmacokinetics of Elbasvir (MK-8742) (MK-8742-009) (NCT NCT01797536)
NCT ID: NCT01797536
Last Updated: 2018-10-25
Results Overview
Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the AUC0-inf of elbasvir.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
31 participants
Primary outcome timeframe
Predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168
Results posted on
2018-10-25
Participant Flow
3 participants from the mild insufficiency arm were mistakenly reenrolled into the moderate arm and received a 2nd single dose of study drug. Data for these 3 participants were excluded from pharmacokinetic analysis of the moderate arm but were included in the safety analysis. An additional 3 participants were enrolled in the moderate arm.
Participant milestones
| Measure |
Mild Hepatic Insufficiency
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
11
|
7
|
8
|
|
Overall Study
COMPLETED
|
8
|
10
|
7
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Mild Hepatic Insufficiency
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
0
|
Baseline Characteristics
The Influence of Hepatic Insufficiency on the Pharmacokinetics of Elbasvir (MK-8742) (MK-8742-009)
Baseline characteristics by cohort
| Measure |
Mild Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=11 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
54 Years
n=5 Participants
|
54 Years
n=7 Participants
|
56 Years
n=5 Participants
|
54 Years
n=4 Participants
|
54.35 Years
n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168Population: Participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment and had available data for the endpoint. Moderate arm summary excludes data for 3 participants incorrectly re-enrolled and dosed in moderate arm after completing dosing and follow-up in the mild insufficiency arm.
Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the AUC0-inf of elbasvir.
Outcome measures
| Measure |
Mild Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Area Under the Curve From 0 to Infinity (AUC0-inf) of Elbasvir
|
1.56 μM•hr
Interval 0.95 to 2.57
|
1.86 μM•hr
Interval 1.1 to 3.16
|
2.28 μM•hr
Interval 1.34 to 3.87
|
2.58 μM•hr
Interval 1.58 to 4.24
|
PRIMARY outcome
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, and 24Population: Participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment and had available data for the endpoint. Moderate arm summary excludes data for 3 participants incorrectly re-enrolled and dosed in moderate arm after completing dosing and follow-up in the mild insufficiency arm.
Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 to determine the AUC0-24hr of elbasvir.
Outcome measures
| Measure |
Mild Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Elbasvir
|
0.87 μM•hr
Interval 0.54 to 1.41
|
0.92 μM•hr
Interval 0.55 to 1.55
|
0.92 μM•hr
Interval 0.55 to 1.54
|
1.45 μM•hr
Interval 0.9 to 2.35
|
PRIMARY outcome
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168Population: Participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment and had available data for the endpoint. Moderate arm summary excludes data for 3 participants incorrectly re-enrolled and dosed in moderate arm after completing dosing and follow-up in the mild insufficiency arm.
Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the Cmax of Elbasvir.
Outcome measures
| Measure |
Mild Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Maximum Concentration (Cmax) of Elbasvir
|
70.1 nM
Interval 42.3 to 116.0
|
83.0 nM
Interval 50.1 to 137.0
|
70.7 nM
Interval 41.3 to 121.0
|
121.0 nM
Interval 73.1 to 200.0
|
PRIMARY outcome
Timeframe: Hour 24Population: Participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment and had available data for the endpoint. Moderate arm summary excludes data for 3 participants incorrectly re-enrolled and dosed in moderate arm after completing dosing and follow-up in the mild insufficiency arm.
Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24, to determine the concentration of elbasvir at Hour 24 was determined.
Outcome measures
| Measure |
Mild Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Concentration at 24 Hours (C24) After Dosing Elbasvir
|
22.9 nM
Interval 14.0 to 37.5
|
25.9 nM
Interval 15.3 to 43.9
|
29.6 nM
Interval 17.4 to 50.1
|
37.7 nM
Interval 23.0 to 61.7
|
PRIMARY outcome
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168Population: Participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment and had available data for the endpoint. Moderate arm summary excludes data for 3 participants incorrectly re-enrolled and dosed in moderate arm after completing dosing and follow-up in the mild insufficiency arm.
Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the maximum concentration (Cmax) of elbasvir. The time to reach Cmax (Tmax) was determined.
Outcome measures
| Measure |
Mild Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of Elbasvir
|
3.50 hour (hr)
Interval 2.0 to 6.0
|
3.50 hour (hr)
Interval 2.0 to 4.0
|
4.00 hour (hr)
Interval 3.0 to 4.0
|
3.50 hour (hr)
Interval 2.0 to 4.0
|
PRIMARY outcome
Timeframe: Predose and Hours 0.5, 1, 2, 3, 4, , 6, 8, 12, 16, 24, 48, 96, 144, and 168Population: Participants who complied with the protocol sufficiently to ensure that generated data were likely to exhibit the effects of treatment and had available data for the endpoint. Moderate arm summary excludes data for 3 participants incorrectly re-enrolled and dosed in moderate arm after completing dosing and follow-up in the mild insufficiency arm.
Blood samples were collected at predose and Hours 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 96, 144, and 168 to determine the t1/2 of elbasvir.
Outcome measures
| Measure |
Mild Hepatic Insufficiency
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 Participants
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Apparent Terminal Half-Life (t1/2) of Elbasvir
|
24.80 hr
Geometric Coefficient of Variation 21.65
|
25.39 hr
Geometric Coefficient of Variation 34.24
|
33.72 hr
Geometric Coefficient of Variation 20.82
|
20.74 hr
Geometric Coefficient of Variation 12.64
|
Adverse Events
Mild Hepatic Insufficiency
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Moderate Hepatic Insufficiency
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Severe Hepatic Insufficiency
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Healthy Participants
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Mild Hepatic Insufficiency
n=8 participants at risk
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=11 participants at risk
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 participants at risk
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 participants at risk
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Psychiatric disorders
Alcohol withdrawal syndrome
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
9.1%
1/11 • Number of events 1 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/7 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
Other adverse events
| Measure |
Mild Hepatic Insufficiency
n=8 participants at risk
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with mild hepatic insufficiency, defined as a score of 5 to 6 on the Child-Pugh scale
|
Moderate Hepatic Insufficiency
n=11 participants at risk
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with moderate hepatic insufficiency, defined as a score of 7 to 9 on the Child-Pugh scale
|
Severe Hepatic Insufficiency
n=7 participants at risk
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants with severe hepatic insufficiency, defined as a score of 10 to 15 on the Child-Pugh scale
|
Healthy Participants
n=8 participants at risk
Single oral dose of 5 x 10 mg capsules of elbasvir administered to participants matched to the mean of all hepatic insufficiency participants for age, gender, and weight
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
9.1%
1/11 • Number of events 1 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/7 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
9.1%
1/11 • Number of events 1 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/7 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
1/8 • Number of events 1 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/11 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/7 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
9.1%
1/11 • Number of events 1 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/7 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
0.00%
0/8 • up to 14 days post-dose (total of 14 days for each panel)
All participants who received study medication. Includes safety data for 3 participants who were enrolled in both mild and moderate hepatic insufficiency arms and received study medication while enrolled in both arms.
|
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 study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
- Publication restrictions are in place
Restriction type: OTHER