Trial Outcomes & Findings for A Study to Assess Pharmacokinetics of Preladenant in Participants With Chronic Hepatic Impairment (P06513) (NCT NCT01465412)
NCT ID: NCT01465412
Last Updated: 2018-09-24
Results Overview
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant.
COMPLETED
PHASE1
42 participants
Pre-dose up to 72 hours postdose
2018-09-24
Participant Flow
Participant milestones
| Measure |
Mild Hepatic Impaired (HI) Part 1
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
9
|
9
|
|
Overall Study
COMPLETED
|
12
|
12
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess Pharmacokinetics of Preladenant in Participants With Chronic Hepatic Impairment (P06513)
Baseline characteristics by cohort
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
55.3 Years
STANDARD_DEVIATION 6.5 • n=5 Participants
|
52.3 Years
STANDARD_DEVIATION 7.1 • n=7 Participants
|
52.2 Years
STANDARD_DEVIATION 4.8 • n=5 Participants
|
50.1 Years
STANDARD_DEVIATION 3.3 • n=4 Participants
|
52.7 Years
STANDARD_DEVIATION 5.9 • n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
34 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Pre-dose up to 72 hours postdosePopulation: All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant.
Outcome measures
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Time of the Last Quantifiable Concentration (AUC 0-t) of Preladenant After a Single Dose of Preladenant
|
97.864 hr*ng/mL
Interval 33.181 to 304.594
|
91.014 hr*ng/mL
Interval 27.457 to 171.81
|
300.667 hr*ng/mL
Interval 81.081 to 571.197
|
115.715 hr*ng/mL
Interval 16.816 to 352.507
|
PRIMARY outcome
Timeframe: Pre-dose up to 72 hours postdosePopulation: All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant.
Outcome measures
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Preladenant After a Single Dose of Preladenant
|
39.380 ng/mL
Interval 15.9 to 61.5
|
30.171 ng/mL
Interval 5.89 to 73.2
|
56.997 ng/mL
Interval 8.95 to 109.0
|
39.735 ng/mL
Interval 4.13 to 113.0
|
SECONDARY outcome
Timeframe: Pre-dose up to 72 hours postdosePopulation: All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of SCH 434748.
Outcome measures
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
AUC 0-t of Preladenant Metabolite SCH 434748 After a Single Dose of Preladenant
|
28.505 hr*ng/mL
Interval 17.858 to 60.434
|
15.395 hr*ng/mL
Interval 0.156 to 45.462
|
60.486 hr*ng/mL
Interval 17.213 to 96.253
|
25.288 hr*ng/mL
Interval 6.399 to 149.982
|
SECONDARY outcome
Timeframe: Pre-dose up to 72 hours postdosePopulation: All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of SCH 434748.
Outcome measures
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
Cmax of Preladenant Metabolite SCH 434748 After a Single Dose of Preladenant
|
10.503 ng/mL
Interval 5.28 to 20.4
|
6.784 ng/mL
Interval 0.624 to 21.4
|
13.983 ng/mL
Interval 4.53 to 52.7
|
9.936 ng/mL
Interval 2.97 to 54.5
|
SECONDARY outcome
Timeframe: Pre-dose up to 72 hours postdosePopulation: All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of SCH 446637.
Outcome measures
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
AUC 0-t of Preladenant Metabolite SCH 446637 After a Single Dose of Preladenant
|
38.262 hr*ng/mL
Interval 18.636 to 87.772
|
24.612 hr*ng/mL
Interval 0.149 to 84.837
|
170.215 hr*ng/mL
Interval 55.366 to 491.013
|
35.421 hr*ng/mL
Interval 10.783 to 70.257
|
SECONDARY outcome
Timeframe: Pre-dose up to 72 hours postdosePopulation: All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of SCH 446637.
Outcome measures
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
Cmax of Preladenant Metabolite SCH 446637 After a Single Dose of Preladenant
|
12.691 ng/mL
Interval 6.47 to 29.1
|
10.004 ng/mL
Interval 0.595 to 24.0
|
21.761 ng/mL
Interval 9.84 to 45.6
|
10.993 ng/mL
Interval 4.91 to 21.4
|
SECONDARY outcome
Timeframe: Pre-dose up to 72 hours postdosePopulation: All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the AUC 0-t of preladenant calculated using free drug concentration.
Outcome measures
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
AUC 0-t of Preladenant Calculated Using Free Drug Concentration After a Single Dose of Preladenant
|
1.605 hr*ng/mL
Interval 0.547 to 6.396
|
1.211 hr*ng/mL
Interval 0.261 to 3.295
|
6.792 hr*ng/mL
Interval 1.133 to 15.708
|
1.681 hr*ng/mL
Interval 0.202 to 6.757
|
SECONDARY outcome
Timeframe: Pre-dose up to 72 hours postdosePopulation: All participants who received an oral dose of preladenant and for whom at least one pharmacokinetic parameter can be calculated for the treatment phase according to the protocol and who did not have any protocol deviation interfering with pharmacokinetics.
For healthy and HI participants blood samples were collected at pre-dose (0 hour) and at 0.50, 1, 2, 4, 6, 12, 16, 24, 30, 36, and 48 hours postdose. Blood samples were also collected for HI participants only at 60 and 72 hours postdose in order to determine the Cmax of preladenant calculated using free drug concentration.
Outcome measures
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 Participants
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 Participants
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 Participants
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 Participants
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
Cmax of Preladenant Calculated Using Free Drug Concentration After a Single Dose of Preladenant
|
0.646 ng/mL
Interval 0.223 to 1.412
|
0.401 ng/mL
Interval 0.13 to 1.129
|
1.288 ng/mL
Interval 0.255 to 2.787
|
0.577 ng/mL
Interval 0.05 to 2.184
|
Adverse Events
Mild Hepatic Impaired (HI) Part 1
Healthy to Match Mild HI Part 1
Moderate HI Part 2
Healthy to Match Moderate HI Part 2
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Mild Hepatic Impaired (HI) Part 1
n=12 participants at risk
Participants with mild chronic liver disease enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Mild HI Part 1
n=12 participants at risk
Healthy volunteers with normal hepatic function matched to participants with mild chronic liver disease by race, age, BMI, and gender, enrolled in Part 1 received one 5-mg preladenant tablet, orally, on Day 1.
|
Moderate HI Part 2
n=9 participants at risk
Participants with moderate chronic liver disease enrolled in Part 2 one 5-mg preladenant tablet, orally, on Day 1.
|
Healthy to Match Moderate HI Part 2
n=9 participants at risk
Healthy volunteers with normal hepatic function matched to participants with moderate chronic liver disease by race, age, BMI, and gender, enrolled in Part 2 received one 5-mg preladenant tablet, orally, on Day 1.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
8.3%
1/12 • Number of events 1 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/12 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/9 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/9 • Up to 7 days
All participants who received an oral dose of preladenant.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/12 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/12 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/9 • Up to 7 days
All participants who received an oral dose of preladenant.
|
11.1%
1/9 • Number of events 1 • Up to 7 days
All participants who received an oral dose of preladenant.
|
|
Nervous system disorders
Dyskinesia
|
0.00%
0/12 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/12 • Up to 7 days
All participants who received an oral dose of preladenant.
|
11.1%
1/9 • Number of events 1 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/9 • Up to 7 days
All participants who received an oral dose of preladenant.
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Number of events 1 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/12 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/9 • Up to 7 days
All participants who received an oral dose of preladenant.
|
0.00%
0/9 • Up to 7 days
All participants who received an oral dose of preladenant.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with regard to proprietary information; the accuracy of the information; and to ensure that the presentation is fairly balanced and in compliance with Food and Drug Administration (FDA) regulations.
- Publication restrictions are in place
Restriction type: OTHER