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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003034-86 | EudraCT Number |
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Hepatic impairment PK study
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1_Without impairment | Experimental | Single, 25 mg dose of PF-05221304 |
|
| Cohort 2_Mild impairment | Experimental | Single, 25 mg dose of PF-05221304 |
|
| Cohort 3_Moderate impairment | Experimental | Single, 25 mg dose of PF-05221304 |
|
| Cohort 4_Severe impairment | Experimental | Single, 25 mg dose of PF-05221304 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-05221304 | Drug | 25 mg dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of PF-05221304 | Cmax was observed directly from data. | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 | 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. | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
| Fraction Unbound (fu) of PF-05221304 | 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. | 4 hours postdose |
| Unbound Cmax (Cmax,u) of PF-05221304 | Cmax,u was calculated by fu*Cmax. | 4 hours postdose |
| Unbound AUCinf (AUCinf,u) of PF-05221304 | AUCinf,u was calculated by fu*AUCinf. | 4 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 | Tmax was observed directly from data as time of first occurrence. | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
| Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 |
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Key Exclusion Criteria:
All subjects -
Healthy/ those without hepatic impairment -
Those with varying degrees of hepatic impairment -
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orlando Clinical Research Center | Orlando | Florida | 32809 | United States | ||
| Pfizer Clinical Research Unit |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Plasma Concentration (Cmax) of PF-05221304 | Cmax was observed directly from data. | The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter (ng/mL) | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer,Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 29, 2019 | Jun 19, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Sep 18, 2017 | Jun 19, 2019 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D015507 | Drugs, Investigational |
| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
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|
AUClast was calculated by linear/Log trapezoidal method. |
| 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
| Unbound AUClast ( AUClast,u) of PF-05221304 | AUClast,u was calculated by fu*AUClast. | 4 hours postdose |
| Apparent Clearance After Oral Dose (CL/F) of PF-05221304 | CL/F was calculated by Dose/AUCinf. | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
| Unbound CL/F (CLu/F) of PF-05221304 | CLu/F was calculated by fu*CL/F. | 4 hours postdose |
| Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 | 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. | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
| Unbound Vz/F (Vz,u/F) of PF-05221304 | Vz,u/F was calculated by fu*Vz/F. | 4 hours postdose |
| Terminal Half-Life ( t½) of PF-05221304 | t1/2 was calculated by loge(2)/kel. | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | Approximately 30 days |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | 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. | 7 days |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | 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. | 7 days |
| Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | 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. | 7 days |
| Number of Participants With Clinical Significant Findings in Vital Signs | 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. | 7 days |
| Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data | 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. | 7 days |
| Brussels |
| B-1070 |
| Belgium |
| Pharmaceutical Research Associates CZ, s.r.o. | Prague | 170 00 | Czechia |
| Nemocnice Na Bulovce | Prague | 180 81 | Czechia |
| Summit Clinical Research s.r.o. | Bratislava | 83101 | Slovakia |
| Univerzitná Nemocnica Bratislava | Bratislava | 83305 | Slovakia |
| BG001 |
| 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| 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. |
| OG002 | 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. |
| OG003 | 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. |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 | 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. | The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram*hour per milliliter (ng*hr/mL) | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
|
|
|
|
| Primary | Fraction Unbound (fu) of PF-05221304 | 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. | The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | 4 hours postdose |
|
|
|
|
| Primary | Unbound Cmax (Cmax,u) of PF-05221304 | Cmax,u was calculated by fu*Cmax. | The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 4 hours postdose |
|
|
|
|
| Primary | Unbound AUCinf (AUCinf,u) of PF-05221304 | AUCinf,u was calculated by fu*AUCinf. | The analysis population was defined as all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 4 hours postdose |
|
|
|
|
| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 | Tmax was observed directly from data as time of first occurrence. | The analysis population included all participants who received 1 dose of PF-05221304 and in whom at least 1 plasma concentration value was reported. | Posted | Median | Full Range | Hours | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
|
|
|
| Secondary | Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 | AUClast was calculated by linear/Log trapezoidal method. | The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
|
|
|
| Secondary | Unbound AUClast ( AUClast,u) of PF-05221304 | AUClast,u was calculated by fu*AUClast. | The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 4 hours postdose |
|
|
|
| Secondary | Apparent Clearance After Oral Dose (CL/F) of PF-05221304 | CL/F was calculated by Dose/AUCinf. | The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour (L/hr) | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
|
|
|
| Secondary | Unbound CL/F (CLu/F) of PF-05221304 | CLu/F was calculated by fu*CL/F. | The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 4 hours postdose |
|
|
|
| Secondary | Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 | 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. | The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
|
|
|
| Secondary | Unbound Vz/F (Vz,u/F) of PF-05221304 | Vz,u/F was calculated by fu*Vz/F. | The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | 4 hours postdose |
|
|
|
| Secondary | Terminal Half-Life ( t½) of PF-05221304 | t1/2 was calculated by loge(2)/kel. | The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Mean | Standard Deviation | Hours | 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose |
|
|
|
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | The analysis population included all participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | Approximately 30 days |
|
|
|
| Secondary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology | 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. | The analysis population included all participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Secondary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry | 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. | The analysis population included all participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Secondary | Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis | 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. | The analysis population included all participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Secondary | Number of Participants With Clinical Significant Findings in Vital Signs | 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. | The analysis population included all participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Secondary | Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data | 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. | The analysis population included all participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | 7 days |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | 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. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG002 | 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. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG003 | 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. | 0 | 6 | 0 | 6 | 0 | 6 |
| Somnolence | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
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.
| ANOVA |
The natural log transformed parameter was used. |
| Mean Difference (Final Values) |
| 124.23 |
| 2-Sided |
| 90 |
| 86.20 |
| 179.03 |
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. |
| Other |
| ANOVA | The natural log transformed parameter was used. | Mean Difference (Final Values) | 118.65 | 2-Sided | 90 | 82.33 | 170.99 | 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. | Other |
| ANOVA |
The natural log transformed parameter was used. |
| Mean Difference (Final Values) |
| 147.0778 |
| 2-Sided |
| 90 |
| 97.3132 |
| 222.2911 |
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. |
| Other |
| ANOVA | The natural log transformed parameter was used. | Mean Difference (Final Values) | 224.7373 | 2-Sided | 90 | 148.6962 | 339.6647 | 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. | Other |
| ANOVA |
The natural log transformed parameter was used. |
| Mean Difference (Final Values) |
| 172.74 |
| 2-Sided |
| 90 |
| 109.56 |
| 272.35 |
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. |
| Other |
| ANOVA | The natural log transformed parameter was used. | Mean Difference (Final Values) | 293.31 | 2-Sided | 90 | 186.04 | 462.44 | 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. | Other |
| ANOVA |
The natural log transformed parameter was used. |
| Mean Difference (Final Values) |
| 182.51 |
| 2-Sided |
| 90 |
| 111.78 |
| 298.02 |
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. |
| Other |
| ANOVA | The natural log transformed parameter was used. | Mean Difference (Final Values) | 266.29 | 2-Sided | 90 | 163.08 | 434.80 | 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. | Other |
| Treatment-related TEAE |
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| Hematocrit <0.8*LLN |
|
| Erythrocytes <0.8*LLN |
|
| Reticulocytes <0.5*LLN |
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| Reticulocytes >1.5*upper limit of normal (ULN) |
|
| Erythrocyte Mean Corpuscular Volume <0.9*LLN |
|
| Erythrocyte Mean Corpuscular Volume >1.1*ULN |
|
| Erythrocyte MCHC <0.9*LLN |
|
| Erythrocyte MCHC >1.1*ULN |
|
| Erythrocyte Mean Corpuscular Hemoglobin <0.9*LLN |
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| Erythrocyte Mean Corpuscular Hemoglobin >1.1*ULN |
|
| Platelets <0.5*LLN |
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| Platelets >1.75*ULN |
|
| Leukocytes <0.6*LLN |
|
| Leukocytes >1.5*ULN |
|
| Lymphocytes <0.8*LLN |
|
| Lymphocytes >1.2*ULN |
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| Neutrophils <0.8*LLN |
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| Neutrophils >1.2*ULN |
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| Basophils >1.2*ULN |
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| Eosinophils >1.2*ULN |
|
| Monocytes >1.2*ULN |
|
| Activated Partial Thromboplastin Time >1.1*ULN |
|
| Prothrombin Time >1.1*ULN |
|
|
| Direct Bilirubin >1.5*ULN |
|
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| Indirect Bilirubin >1.5*ULN |
|
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| Aspartate Aminotransferase >3.0*ULN |
|
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| Alanine Aminotransferase >3.0*ULN |
|
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| Gamma Glutamyl Transferase >3.0*ULN |
|
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| Alkaline Phosphatase >3.0*ULN |
|
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| Protein <0.8*LLN |
|
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| Protein >1.2*ULN |
|
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| Albumin <0.8*LLN |
|
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| Albumin >1.2*ULN |
|
|
| Blood Urea Nitrogen >1.3*ULN |
|
|
| Creatinine >1.3*ULN |
|
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| Urate >1.2*ULN |
|
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| Sodium <0.95*LLN |
|
|
| Sodium >1.05*ULN |
|
|
| Potassium <0.9*LLN |
|
|
| Potassium >1.1*ULN |
|
|
| Chloride <0.9*LLN |
|
|
| Chloride >1.1*ULN |
|
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| Calcium <0.9*LLN |
|
|
| Calcium >1.1*ULN |
|
|
| Phosphate <0.8*LLN |
|
|
| Phosphate >1.2*ULN |
|
|
| Bicarbonate <0.9*LLN |
|
|
| Bicarbonate >1.1*ULN |
|
|
| Creatine Kinase >2.0*ULN |
|
|
| Fasting Glucose <0.6*LLN |
|
|
| Fasting-Glucose >1.5*ULN |
|
|
|
| Scalar Ketones >=1 |
|
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| Scalar Urine Protein >=1 |
|
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| Scalar Urine Hemoglobin >=1 |
|
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| Scalar Urobilinogen >=1 |
|
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| Scalar Urine Bilirubin >=1 |
|
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| Scalar Nitrite >=1 |
|
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| Scalar Leukocyte Esterase >=1 |
|
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| Urine Erythrocytes >=20 (/high power field [HPF]) |
|
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| Urine Leukocytes >=20 (/HPF) |
|
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| Hyaline Casts >1 (/low power field [LPF]) |
|
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| Scalar Bacteria >20 |
|
|