Study of PF-05221304 in Subjects With Varying Degrees of Hepatic Impairment
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT03309202
Collaborator
(none)
24
6
4
6.9
4
0.6
Study Details
Study Description
Brief Summary
Hepatic impairment PK study
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of varying degrees of hepatic impairment on the plasma pharmacokinetics (total and unbound) of PF-05221304 after a single oral dose administered in the fed state.
Study Design
Study Type:
Interventional
Actual Enrollment
:
24 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL COHORT STUDY TO COMPARE THE PHARMACOKINETICS OF PF-05221304 IN ADULT SUBJECTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO SUBJECTS WITHOUT HEPATIC IMPAIRMENT
Actual Study Start Date
:
Dec 19, 2017
Actual Primary Completion Date
:
Jun 26, 2018
Actual Study Completion Date
:
Jul 18, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1_Without impairment Single, 25 mg dose of PF-05221304 |
Drug: PF-05221304
25 mg dose
Other Names:
|
| Experimental: Cohort 2_Mild impairment Single, 25 mg dose of PF-05221304 |
Drug: PF-05221304
25 mg dose
Other Names:
|
| Experimental: Cohort 3_Moderate impairment Single, 25 mg dose of PF-05221304 |
Drug: PF-05221304
25 mg dose
Other Names:
|
| Experimental: Cohort 4_Severe impairment Single, 25 mg dose of PF-05221304 |
Drug: PF-05221304
25 mg dose
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Plasma Concentration (Cmax) of PF-05221304 [0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose]
Cmax was observed directly from data.
- Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 [0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose]
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.
- Fraction Unbound (fu) of PF-05221304 [4 hours postdose]
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.
- Unbound Cmax (Cmax,u) of PF-05221304 [4 hours postdose]
Cmax,u was calculated by fu*Cmax.
- Unbound AUCinf (AUCinf,u) of PF-05221304 [4 hours postdose]
AUCinf,u was calculated by fu*AUCinf.
Secondary Outcome Measures
- Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 [0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose]
Tmax was observed directly from data as time of first occurrence.
- Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 [0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose]
AUClast was calculated by linear/Log trapezoidal method.
- Unbound AUClast ( AUClast,u) of PF-05221304 [4 hours postdose]
AUClast,u was calculated by fu*AUClast.
- Apparent Clearance After Oral Dose (CL/F) of PF-05221304 [0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose]
CL/F was calculated by Dose/AUCinf.
- Unbound CL/F (CLu/F) of PF-05221304 [4 hours postdose]
CLu/F was calculated by fu*CL/F.
- Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 [0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose]
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.
- Unbound Vz/F (Vz,u/F) of PF-05221304 [4 hours postdose]
Vz,u/F was calculated by fu*Vz/F.
- Terminal Half-Life ( t½) of PF-05221304 [0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose]
t1/2 was calculated by loge(2)/kel.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Approximately 30 days]
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.
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology [7 days]
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.
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry [7 days]
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.
- Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis [7 days]
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.
- Number of Participants With Clinical Significant Findings in Vital Signs [7 days]
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.
- Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data [7 days]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Key Exclusion Criteria:
All subjects -
-
Adults <18 years of age and >70 years of age
-
BMI < 17.5 and > 35.4 kg/m2
-
HIV positive
-
Conditions that affect drug absorption
-
Positive breath alcohol test
Healthy/ those without hepatic impairment -
-
Known or suspected hepatic impairment
-
Evidence of Hepatitis B or C
-
On any chronic medications
Those with varying degrees of hepatic impairment -
-
Not meeting Classification A, B, or C of hepatic impairment based on Child-Pugh Classification
-
Evidence of Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy
-
Recent GI bleed
-
Moderate or severe renal impairment
-
Hepatic encephalopathy Grade 3 or higher
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Orlando Clinical Research Center | Orlando | Florida | United States | 32809 |
| 2 | Pfizer Clinical Research Unit | Brussels | Belgium | B-1070 | |
| 3 | Pharmaceutical Research Associates CZ, s.r.o. | Praha 7 | Czechia | 170 00 | |
| 4 | Nemocnice Na Bulovce | Praha 8 | Czechia | 180 81 | |
| 5 | Summit Clinical Research s.r.o. | Bratislava | Slovakia | 83101 | |
| 6 | Univerzitná Nemocnica Bratislava | Bratislava | Slovakia | 83305 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
- To obtain contact information for a study center near you, click here.
- To obtain contact information for a study center near you, click here.
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03309202
Other Study ID Numbers:
- C1171006
- 2017-003034-86
First Posted:
Oct 13, 2017
Last Update Posted:
Aug 8, 2019
Last Verified:
Jun 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 6 | 6 | 6 | 6 |
| COMPLETED | 5 | 6 | 6 | 6 |
| NOT COMPLETED | 1 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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 of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 24 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
6
100%
|
6
100%
|
4
66.7%
|
5
83.3%
|
21
87.5%
|
| >=65 years |
0
0%
|
0
0%
|
2
33.3%
|
1
16.7%
|
3
12.5%
|
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
56.17
(2.23)
|
55.50
(9.73)
|
60.00
(5.97)
|
55.33
(7.50)
|
56.75
(6.74)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
33.3%
|
1
16.7%
|
2
33.3%
|
1
16.7%
|
6
25%
|
| Male |
4
66.7%
|
5
83.3%
|
4
66.7%
|
5
83.3%
|
18
75%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| White |
4
66.7%
|
5
83.3%
|
6
100%
|
6
100%
|
21
87.5%
|
| Black or African American |
2
33.3%
|
0
0%
|
0
0%
|
0
0%
|
2
8.3%
|
| Asian |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
4.2%
|
Outcome Measures
| Title | Maximum Plasma Concentration (Cmax) of PF-05221304 |
|---|---|
| Description | Cmax was observed directly from data. |
| Time Frame | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [Nanogram per milliliter (ng/mL)] |
1220
(20)
|
1591
(33)
|
1433
(20)
|
1592
(27)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 2 (Mild Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 130.47 | |
| Confidence Interval |
(2-Sided) 90% 101.57 to 167.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 2 (Mild Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 3 (Moderate Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 117.49 | |
| Confidence Interval |
(2-Sided) 90% 91.46 to 150.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 3 (Moderate Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 130.55 | |
| Confidence Interval |
(2-Sided) 90% 101.63 to 167.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 4 (Severe Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
| Title | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 |
|---|---|
| Description | 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. |
| Time Frame | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [Nanogram*hour per milliliter (ng*hr/mL)] |
17520
(36)
|
23890
(41)
|
21770
(31)
|
20790
(43)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 2 (Mild Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 136.37 | |
| Confidence Interval |
(2-Sided) 90% 94.63 to 196.53 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 2 (Mild Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 3 (Moderate Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 124.23 | |
| Confidence Interval |
(2-Sided) 90% 86.20 to 179.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 3 (Moderate Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 118.65 | |
| Confidence Interval |
(2-Sided) 90% 82.33 to 170.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 4 (Severe Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
| Title | Fraction Unbound (fu) of PF-05221304 |
|---|---|
| Description | 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. |
| Time Frame | 4 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.005519
(44)
|
0.006883
(55)
|
0.008117
(45)
|
0.01240
(26)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 2 (Mild Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 124.7309 | |
| Confidence Interval |
(2-Sided) 90% 82.5275 to 188.5165 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 2 (Mild Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 3 (Moderate Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 147.0778 | |
| Confidence Interval |
(2-Sided) 90% 97.3132 to 222.2911 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 3 (Moderate Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 224.7373 | |
| Confidence Interval |
(2-Sided) 90% 148.6962 to 339.6647 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 4 (Severe Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
| Title | Unbound Cmax (Cmax,u) of PF-05221304 |
|---|---|
| Description | Cmax,u was calculated by fu*Cmax. |
| Time Frame | 4 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
6.731
(57)
|
10.94
(44)
|
11.63
(48)
|
19.74
(43)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 2 (Mild Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 162.58 | |
| Confidence Interval |
(2-Sided) 90% 103.12 to 256.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 2 (Mild Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 3 (Moderate Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 172.74 | |
| Confidence Interval |
(2-Sided) 90% 109.56 to 272.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 3 (Moderate Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 293.31 | |
| Confidence Interval |
(2-Sided) 90% 186.04 to 462.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 4 (Severe Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
| Title | Unbound AUCinf (AUCinf,u) of PF-05221304 |
|---|---|
| Description | AUCinf,u was calculated by fu*AUCinf. |
| Time Frame | 4 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was defined as all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
96.78
(75)
|
164.4
(34)
|
176.6
(51)
|
257.7
(45)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 2 (Mild Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 169.84 | |
| Confidence Interval |
(2-Sided) 90% 104.02 to 277.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 2 (Mild Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 3 (Moderate Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 182.51 | |
| Confidence Interval |
(2-Sided) 90% 111.78 to 298.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 3 (Moderate Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1 (Without Hepatic Impairment), Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 266.29 | |
| Confidence Interval |
(2-Sided) 90% 163.08 to 434.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimate mean difference was derived from ratio (%) of adjusted geometric means of Test and Reference.Cohort 4 (Severe Hepatic Impairment) was Test and Cohort 1 (Without Hepatic Impairment) was Reference. | |
| Title | Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 |
|---|---|
| Description | Tmax was observed directly from data as time of first occurrence. |
| Time Frame | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Median (Full Range) [Hours] |
4.01
|
4.95
|
4.50
|
4.00
|
| Title | Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 |
|---|---|
| Description | AUClast was calculated by linear/Log trapezoidal method. |
| Time Frame | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
17400
(36)
|
23670
(40)
|
21680
(31)
|
20700
(43)
|
| Title | Unbound AUClast ( AUClast,u) of PF-05221304 |
|---|---|
| Description | AUClast,u was calculated by fu*AUClast. |
| Time Frame | 4 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
96.07
(75)
|
163.3
(34)
|
175.9
(51)
|
256.7
(45)
|
| Title | Apparent Clearance After Oral Dose (CL/F) of PF-05221304 |
|---|---|
| Description | CL/F was calculated by Dose/AUCinf. |
| Time Frame | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [Liter per hour (L/hr)] |
1.427
(36)
|
1.048
(41)
|
1.151
(31)
|
1.202
(43)
|
| Title | Unbound CL/F (CLu/F) of PF-05221304 |
|---|---|
| Description | CLu/F was calculated by fu*CL/F. |
| Time Frame | 4 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [L/hr] |
258.7
(75)
|
152.0
(33)
|
141.6
(51)
|
97.02
(45)
|
| Title | Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 |
|---|---|
| Description | 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. |
| Time Frame | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters] |
34.94
(35)
|
24.53
(24)
|
23.16
(28)
|
23.97
(23)
|
| Title | Unbound Vz/F (Vz,u/F) of PF-05221304 |
|---|---|
| Description | Vz,u/F was calculated by fu*Vz/F. |
| Time Frame | 4 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters] |
6334
(69)
|
3563
(51)
|
2854
(59)
|
1931
(37)
|
| Title | Terminal Half-Life ( t½) of PF-05221304 |
|---|---|
| Description | t1/2 was calculated by loge(2)/kel. |
| Time Frame | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [Hours] |
17.43
(4.7471)
|
17.25
(6.8372)
|
14.30
(3.4135)
|
14.76
(5.7937)
|
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
|---|---|
| Description | 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. |
| Time Frame | Approximately 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received at least 1 dose of study medication. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| All-causality TEAE |
0
0%
|
1
16.7%
|
2
33.3%
|
0
0%
|
| Treatment-related TEAE |
0
0%
|
1
16.7%
|
1
16.7%
|
0
0%
|
| Title | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology |
|---|---|
| Description | 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. |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received at least 1 dose of study medication. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Hemoglobin <0.8*lower limit of normal (LLN) |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| Hematocrit <0.8*LLN |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| Erythrocytes <0.8*LLN |
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
| Reticulocytes <0.5*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Reticulocytes >1.5*upper limit of normal (ULN) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Erythrocyte Mean Corpuscular Volume <0.9*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Erythrocyte Mean Corpuscular Volume >1.1*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Erythrocyte MCHC <0.9*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Erythrocyte MCHC >1.1*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Erythrocyte Mean Corpuscular Hemoglobin <0.9*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Erythrocyte Mean Corpuscular Hemoglobin >1.1*ULN |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Platelets <0.5*LLN |
0
0%
|
0
0%
|
3
50%
|
2
33.3%
|
| Platelets >1.75*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Leukocytes <0.6*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Leukocytes >1.5*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Lymphocytes <0.8*LLN |
0
0%
|
0
0%
|
2
33.3%
|
1
16.7%
|
| Lymphocytes >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Neutrophils <0.8*LLN |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Neutrophils >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Basophils >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Eosinophils >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Monocytes >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Activated Partial Thromboplastin Time >1.1*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Prothrombin Time >1.1*ULN |
0
0%
|
0
0%
|
1
16.7%
|
3
50%
|
| Title | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry |
|---|---|
| Description | 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. |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received at least 1 dose of study medication. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Bilirubin >1.5*ULN |
0
0%
|
0
0%
|
1
16.7%
|
5
83.3%
|
| Direct Bilirubin >1.5*ULN |
0
0%
|
0
0%
|
0
0%
|
|
| Indirect Bilirubin >1.5*ULN |
0
0%
|
0
0%
|
0
0%
|
2
33.3%
|
| Aspartate Aminotransferase >3.0*ULN |
0
0%
|
0
0%
|
1
16.7%
|
2
33.3%
|
| Alanine Aminotransferase >3.0*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Gamma Glutamyl Transferase >3.0*ULN |
0
0%
|
1
16.7%
|
0
0%
|
2
33.3%
|
| Alkaline Phosphatase >3.0*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Protein <0.8*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Protein >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Albumin <0.8*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Albumin >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Blood Urea Nitrogen >1.3*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine >1.3*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Urate >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sodium <0.95*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sodium >1.05*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Potassium <0.9*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Potassium >1.1*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Chloride <0.9*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Chloride >1.1*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Calcium <0.9*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Calcium >1.1*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Phosphate <0.8*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Phosphate >1.2*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Bicarbonate <0.9*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Bicarbonate >1.1*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatine Kinase >2.0*ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Fasting Glucose <0.6*LLN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Fasting-Glucose >1.5*ULN |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Title | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis |
|---|---|
| Description | 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. |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received at least 1 dose of study medication. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Scalar Urine Glucose >=1 |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Scalar Ketones >=1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Scalar Urine Protein >=1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Scalar Urine Hemoglobin >=1 |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| Scalar Urobilinogen >=1 |
0
0%
|
0
0%
|
1
16.7%
|
3
50%
|
| Scalar Urine Bilirubin >=1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Scalar Nitrite >=1 |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Scalar Leukocyte Esterase >=1 |
1
16.7%
|
1
16.7%
|
2
33.3%
|
1
16.7%
|
| Urine Erythrocytes >=20 (/high power field [HPF]) |
0
0%
|
0
0%
|
0
0%
|
|
| Urine Leukocytes >=20 (/HPF) |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Hyaline Casts >1 (/low power field [LPF]) |
1
16.7%
|
1
16.7%
|
||
| Scalar Bacteria >20 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Clinical Significant Findings in Vital Signs |
|---|---|
| Description | 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. |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received at least 1 dose of study medication. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data |
|---|---|
| Description | 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. |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received at least 1 dose of study medication. |
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 6 | 6 | 6 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | 30 days | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||||
| Arm/Group Title | Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) | ||||
| Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||
Serious Adverse Events |
||||||||
| Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Cohort 1 (Without Hepatic Impairment) | Cohort 2 (Mild Hepatic Impairment) | Cohort 3 (Moderate Hepatic Impairment) | Cohort 4 (Severe Hepatic Impairment) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/6 (0%) | ||||
| Infections and infestations | ||||||||
| Influenza | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | ||||
| Nervous system disorders | ||||||||
| Somnolence | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Blister | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer,Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03309202
Other Study ID Numbers:
- C1171006
- 2017-003034-86
First Posted:
Oct 13, 2017
Last Update Posted:
Aug 8, 2019
Last Verified:
Jun 1, 2019