Trial Outcomes & Findings for Study of PF-05221304 in Subjects With Varying Degrees of Hepatic Impairment (NCT NCT03309202)
NCT ID: NCT03309202
Last Updated: 2019-08-08
Results Overview
Cmax was observed directly from data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Results posted on
2019-08-08
Participant Flow
Recruitment for participants in Cohorts 3 and 4 initiated first and recruitment for participants in Cohort 2 started when approximately 50% of total participants across Cohorts 3 and 4 had been dosed. Participants in Cohort 1 were recruited last to match the average demographics across the pooled Cohorts 2 through 4.
A total of 24 subjects with 4 varying degrees of hepatic function were enrolled into the study to ensure that up to 6 evaluable subjects in each of the 4 hepatic function cohorts complete the study.
Participant milestones
| Measure |
Cohort 1 (Without Hepatic Impairment)
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
5
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1 (Without Hepatic Impairment)
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Study of PF-05221304 in Subjects With Varying Degrees of Hepatic Impairment
Baseline characteristics by cohort
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Total
n=24 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
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Age, Continuous
|
56.17 Years
STANDARD_DEVIATION 2.23 • n=5 Participants
|
55.50 Years
STANDARD_DEVIATION 9.73 • n=7 Participants
|
60.00 Years
STANDARD_DEVIATION 5.97 • n=5 Participants
|
55.33 Years
STANDARD_DEVIATION 7.50 • n=4 Participants
|
56.75 Years
STANDARD_DEVIATION 6.74 • n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdosePopulation: The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported.
Cmax was observed directly from data.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of PF-05221304
|
1220 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 20
|
1591 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 33
|
1433 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 20
|
1592 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 27
|
PRIMARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdosePopulation: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
AUCinf was calculated by AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304
|
17520 Nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 36
|
23890 Nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 41
|
21770 Nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 31
|
20790 Nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 43
|
PRIMARY outcome
Timeframe: 4 hours postdosePopulation: The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported.
fu was the fraction of PF-05221304 unbound in plasma. fu was calculated based on the post-dialysis plasma concentrations, post-dialysis buffer concentrations, collected post-dialysis plasma and post-dialysis buffer sample volume (assuming no volume shift prior to and after dialysis), and the total plasma concentrations.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Fraction Unbound (fu) of PF-05221304
|
0.005519 Ratio
Geometric Coefficient of Variation 44
|
0.006883 Ratio
Geometric Coefficient of Variation 55
|
0.008117 Ratio
Geometric Coefficient of Variation 45
|
0.01240 Ratio
Geometric Coefficient of Variation 26
|
PRIMARY outcome
Timeframe: 4 hours postdosePopulation: The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported.
Cmax,u was calculated by fu\*Cmax.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Unbound Cmax (Cmax,u) of PF-05221304
|
6.731 ng/mL
Geometric Coefficient of Variation 57
|
10.94 ng/mL
Geometric Coefficient of Variation 44
|
11.63 ng/mL
Geometric Coefficient of Variation 48
|
19.74 ng/mL
Geometric Coefficient of Variation 43
|
PRIMARY outcome
Timeframe: 4 hours postdosePopulation: The analysis population was defined as all participants dosed who had at least 1 of the PK parameters of primary interest.
AUCinf,u was calculated by fu\*AUCinf.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Unbound AUCinf (AUCinf,u) of PF-05221304
|
96.78 ng*hr/mL
Geometric Coefficient of Variation 75
|
164.4 ng*hr/mL
Geometric Coefficient of Variation 34
|
176.6 ng*hr/mL
Geometric Coefficient of Variation 51
|
257.7 ng*hr/mL
Geometric Coefficient of Variation 45
|
SECONDARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdosePopulation: The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported.
Tmax was observed directly from data as time of first occurrence.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304
|
4.01 Hours
Interval 1.98 to 4.93
|
4.95 Hours
Interval 2.95 to 5.0
|
4.50 Hours
Interval 1.02 to 5.02
|
4.00 Hours
Interval 0.917 to 5.0
|
SECONDARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdosePopulation: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
AUClast was calculated by linear/Log trapezoidal method.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304
|
17400 ng*hr/mL
Geometric Coefficient of Variation 36
|
23670 ng*hr/mL
Geometric Coefficient of Variation 40
|
21680 ng*hr/mL
Geometric Coefficient of Variation 31
|
20700 ng*hr/mL
Geometric Coefficient of Variation 43
|
SECONDARY outcome
Timeframe: 4 hours postdosePopulation: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
AUClast,u was calculated by fu\*AUClast.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Unbound AUClast ( AUClast,u) of PF-05221304
|
96.07 ng*hr/mL
Geometric Coefficient of Variation 75
|
163.3 ng*hr/mL
Geometric Coefficient of Variation 34
|
175.9 ng*hr/mL
Geometric Coefficient of Variation 51
|
256.7 ng*hr/mL
Geometric Coefficient of Variation 45
|
SECONDARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdosePopulation: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
CL/F was calculated by Dose/AUCinf.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Apparent Clearance After Oral Dose (CL/F) of PF-05221304
|
1.427 Liter per hour (L/hr)
Geometric Coefficient of Variation 36
|
1.048 Liter per hour (L/hr)
Geometric Coefficient of Variation 41
|
1.151 Liter per hour (L/hr)
Geometric Coefficient of Variation 31
|
1.202 Liter per hour (L/hr)
Geometric Coefficient of Variation 43
|
SECONDARY outcome
Timeframe: 4 hours postdosePopulation: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
CLu/F was calculated by fu\*CL/F.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Unbound CL/F (CLu/F) of PF-05221304
|
258.7 L/hr
Geometric Coefficient of Variation 75
|
152.0 L/hr
Geometric Coefficient of Variation 33
|
141.6 L/hr
Geometric Coefficient of Variation 51
|
97.02 L/hr
Geometric Coefficient of Variation 45
|
SECONDARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdosePopulation: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
Vz/F was calculated by Dose/(AUCinf\*kel). kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304
|
34.94 Liters
Geometric Coefficient of Variation 35
|
24.53 Liters
Geometric Coefficient of Variation 24
|
23.16 Liters
Geometric Coefficient of Variation 28
|
23.97 Liters
Geometric Coefficient of Variation 23
|
SECONDARY outcome
Timeframe: 4 hours postdosePopulation: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
Vz,u/F was calculated by fu\*Vz/F.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Unbound Vz/F (Vz,u/F) of PF-05221304
|
6334 Liters
Geometric Coefficient of Variation 69
|
3563 Liters
Geometric Coefficient of Variation 51
|
2854 Liters
Geometric Coefficient of Variation 59
|
1931 Liters
Geometric Coefficient of Variation 37
|
SECONDARY outcome
Timeframe: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdosePopulation: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
t1/2 was calculated by loge(2)/kel.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Terminal Half-Life ( t½) of PF-05221304
|
17.43 Hours
Standard Deviation 4.7471
|
17.25 Hours
Standard Deviation 6.8372
|
14.30 Hours
Standard Deviation 3.4135
|
14.76 Hours
Standard Deviation 5.7937
|
SECONDARY outcome
Timeframe: Approximately 30 daysPopulation: The analysis population included all participants who received at least 1 dose of study medication.
An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event did not need to have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Number of participants with both all-causality and treatment-related TEAEs are presented below.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
All-causality TEAE
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Treatment-related TEAE
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 7 daysPopulation: The analysis population included all participants who received at least 1 dose of study medication.
Hematology evaluation included: hemoglobin, hematocrit, erythrocytes, reticulocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin concentration (MCHC), erythrocyte mean corpuscular hemoglobin, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time and prothrombin time.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Hemoglobin <0.8*lower limit of normal (LLN)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Hematocrit <0.8*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Erythrocytes <0.8*LLN
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Reticulocytes <0.5*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Reticulocytes >1.5*upper limit of normal (ULN)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Erythrocyte Mean Corpuscular Volume <0.9*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Erythrocyte Mean Corpuscular Volume >1.1*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Erythrocyte MCHC <0.9*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Erythrocyte MCHC >1.1*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Erythrocyte Mean Corpuscular Hemoglobin <0.9*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Erythrocyte Mean Corpuscular Hemoglobin >1.1*ULN
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Platelets <0.5*LLN
|
0 Participants
|
0 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Platelets >1.75*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Leukocytes <0.6*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Leukocytes >1.5*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Lymphocytes <0.8*LLN
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Lymphocytes >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Neutrophils <0.8*LLN
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Neutrophils >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Basophils >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Eosinophils >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Monocytes >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Activated Partial Thromboplastin Time >1.1*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology
Prothrombin Time >1.1*ULN
|
0 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 7 daysPopulation: The analysis population included all participants who received at least 1 dose of study medication.
Clinical chemistry evaluation included: bilirubin, direct/indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase , alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, phosphate, bicarbonate, creatine kinase, and fasting glucose.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Urate >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Bilirubin >1.5*ULN
|
0 Participants
|
0 Participants
|
1 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Direct Bilirubin >1.5*ULN
|
—
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Indirect Bilirubin >1.5*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Aspartate Aminotransferase >3.0*ULN
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Alanine Aminotransferase >3.0*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Gamma Glutamyl Transferase >3.0*ULN
|
0 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Alkaline Phosphatase >3.0*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Protein <0.8*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Protein >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Albumin <0.8*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Albumin >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Blood Urea Nitrogen >1.3*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Creatinine >1.3*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Sodium <0.95*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Sodium >1.05*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Potassium <0.9*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Potassium >1.1*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Chloride <0.9*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Chloride >1.1*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Calcium <0.9*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Calcium >1.1*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Phosphate <0.8*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Phosphate >1.2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Bicarbonate <0.9*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Bicarbonate >1.1*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Creatine Kinase >2.0*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Fasting Glucose <0.6*LLN
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry
Fasting-Glucose >1.5*ULN
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 7 daysPopulation: The analysis population included all participants who received at least 1 dose of study medication.
Urinalysis evaluation included: scalar urine glucose, scalar ketones, scalar urine protein, scalar urine hemoglobin, scalar urobilinogen, scalar urine bilirubin, scalar nitrite, scalar leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and scalar bacteria.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Urine Glucose >=1
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Ketones >=1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Urine Protein >=1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Urine Hemoglobin >=1
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Urobilinogen >=1
|
0 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Urine Bilirubin >=1
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Nitrite >=1
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Leukocyte Esterase >=1
|
1 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Urine Erythrocytes >=20 (/high power field [HPF])
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Urine Leukocytes >=20 (/HPF)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Hyaline Casts >1 (/low power field [LPF])
|
—
|
1 Participants
|
1 Participants
|
—
|
|
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis
Scalar Bacteria >20
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 7 daysPopulation: The analysis population included all participants who received at least 1 dose of study medication.
Vital signs evaluation included: sitting systolic and diastolic blood pressure (BP), and sitting pulse rate. Clinically significant findings in vital signs were determined by the investigator.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Number of Participants With Clinical Significant Findings in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 7 daysPopulation: The analysis population included all participants who received at least 1 dose of study medication.
ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), QT interval corrected for heart rate using Fridericia's formula (QTcF interval), and heart rate. Clinically significant findings in ECG data were determined by the investigator.
Outcome measures
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 Participants
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 Participants
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Cohort 1 (Without Hepatic Impairment)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 2 (Mild Hepatic Impairment)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 3 (Moderate Hepatic Impairment)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 4 (Severe Hepatic Impairment)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1 (Without Hepatic Impairment)
n=6 participants at risk
Participants in this cohort had no hepatic impairment. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in Clinical Research Unit (CRU) from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 2 (Mild Hepatic Impairment)
n=6 participants at risk
Participants in this cohort met the criteria of Class A (5 to 6 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 3 (Moderate Hepatic Impairment)
n=6 participants at risk
Participants in this cohort met the criteria of Class B (7 to 9 points) in Child-Pugh Score.PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
Cohort 4 (Severe Hepatic Impairment)
n=6 participants at risk
Participants in this cohort met the criteria of Class C (10 to 15 points) in Child-Pugh Score. PF-05221304 was administered as a single oral 25 mg dose in fed state on Study Day 1. Participants were hospitalized in CRU from Study Days 1 to 3, and continued inpatient stay or daily outpatient visits to CRU from Days 4 to 7.
|
|---|---|---|---|---|
|
Infections and infestations
Influenza
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
16.7%
1/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
16.7%
1/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
16.7%
1/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
0.00%
0/6 • 30 days
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER