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| ID | Type | Description | Link |
|---|---|---|---|
| HEPATIC IMPAIRMENT | Other Identifier | Alias Study Number | |
| 2019-003480-21 | EudraCT Number |
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The study is proposed to characterize the effect of varying degrees of hepatic impairment on the plasma PK of PF-06835919
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-06835919 with severe hepatic impairement | Experimental | This arm includes participants with severe hepatic impairment who will receive a 25mg oral dose of PF-06835919 |
|
| PF-06835919 with moderate hepatic impairement | Experimental | This arm includes participants with moderate hepatic impairment who will receive a 25mg oral dose of PF-06835919 |
|
| PF-06835919 with mild hepatic impairement | Experimental | This arm includes participants with mild hepatic impairment who will receive a 25mg oral dose of PF-06835919 |
|
| PF-06835919 without hepatic impairment | Experimental | This arm includes participants without hepatic impairment who will receive a 25mg oral dose of PF-06835919 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-06835919 25 mg | Drug | PF-06835919 in 25 mg oral tablet will be administered on Day 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06835919 | AUCinf was defined as area under the plasma concentration time curve from time 0 extrapolated to infinite time. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
| Maximum Plasma Concentration (Cmax) of PF-06835919 | Cmax was defined as maximum plasma concentration of PF-06835919 and observed directly from data. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
| Unbound Area Under The Plasma Concentration-Time Curve From Time 0 Extrapolated To Infinite Time (AUCinf,u) of PF-06835919 | AUCinf,u was defined as unbound area under the plasma concentration time curve from time 0 extrapolated to infinite time. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
| Unbound Maximum Plasma Concentration (Cmax,u) of PF-06835919 | Cmax,u was defined as unbound maximum plasma concentration. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
| Fraction of Drug Unbound (fu) of PF-06835919 | The fraction of PF-06835919 unbound in plasma (fu) was determined at approximately the expected Tmax in each participant. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AE (TEAE) was defined as an AE with onset date occurring during the on-treatment period. AEs included all SAEs and non-SAEs. |
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Inclusion Criteria:
Exclusion Criteria:
(Participants who have undergone cholecystectomy and/or appendectomy are eligible for this study as long as the surgery occurred more than 6 months prior to Screening)..
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Clinical Research Unit - Brussels | Brussels | Bruxelles-capitale, Région de | B-1070 | Belgium | ||
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| Label | URL |
|---|---|
| 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 34 participants were screened, of whom 11 had screen failure and 23 entered the study. There were 6, 6, 6 and 5 participants in the without hepatic impairment group, mild hepatic impairment group, moderate hepatic impairment group and severe hepatic impairment group, respectively. All of the 23 treated participants received their assigned treatment, and no participant discontinued.
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| ID | Title | Description |
|---|---|---|
| FG000 | Without Hepatic Impairment | This arm included participants without hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| FG001 | Mild Hepatic Impairment | This arm included participants with mild hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| FG002 | Moderate Hepatic Impairment | This arm included participants with moderate hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| FG003 | Severe Hepatic Impairment | This arm included participants with severe hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety Analysis Set included all participants randomly assigned to investigational product and who took at least 1 dose of investigational product.
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| ID | Title | Description |
|---|---|---|
| BG000 | Without Hepatic Impairment | This arm included participants without hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| BG001 | Mild Hepatic Impairment |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | 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 | Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06835919 | AUCinf was defined as area under the plasma concentration time curve from time 0 extrapolated to infinite time. | The PK parameter 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 | nanogram*hour per milliliter (ng*hr/mL) | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
|
Baseline (Day 1) up to follow-up (Day 31)
All participants randomly assigned to investigational product and who took at least 1 dose of investigational product.
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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 | Without Hepatic Impairment | This arm included participants without hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA v24.0 | 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 |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 18, 2020 | Jun 29, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 3, 2021 | Jun 29, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C000730020 | PF-06835919 |
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| Baseline (Day 1) up to follow-up (Day 31) |
| Number of Participants With Clinically Significant Change (Chg) From Baseline in Laboratory Tests | To determine if there were any clinically significant laboratory abnormalities, hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular hemoglobin, mean corpuscular volume, platelet count, lymphocytes, neutrophils, activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio), clinical chemistry (bilirubin, direct and indirect bilirubin, gamma glutamyl transferase, albumin, urea nitrogen, glucose) and urinalysis (glucose, protein, hemoglobin, urobilinogen, nitrite) tests were assessed. Each parameter was evaluated against commonly used and widely accepted criteria. | Baseline (Day 1) up to Day 6 |
| Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiograms (ECGs) | ECG endpoints (PR interval, QRS interval, QT interval and QTcF) meeting the criteria of potential clinical concern were summarized by treatment using categories as defined: 1. PR max. ≥300ms, %Chg ≥25/50%; 3. QRS max. ≥140ms，%Chg ≥50%; 3.maximum post-dose QTcF 450 - ≤480msec, 480 - ≤500msec and >500msec, 30<Chg≤60 and Chg>60. | Baseline (Day 1) up to Day 6 |
| Pharmaceutical Research Associates CZ, s.r.o. |
| Prague |
| 170 00 |
| Czechia |
| Summit Clinical Research, s.r.o., | Bratislava | 83101 | Slovakia |
This arm included participants with mild hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1.
| BG002 | Moderate Hepatic Impairment | This arm included participants with moderate hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| BG003 | Severe Hepatic Impairment | This arm included participants with severe hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
This arm included participants with mild hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| OG002 | Moderate Hepatic Impairment | This arm included participants with moderate hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
| OG003 | Severe Hepatic Impairment | This arm included participants with severe hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. |
|
|
|
| Primary | Maximum Plasma Concentration (Cmax) of PF-06835919 | Cmax was defined as maximum plasma concentration of PF-06835919 and observed directly from data. | The PK parameter 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/mL | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
|
|
|
|
| Primary | Unbound Area Under The Plasma Concentration-Time Curve From Time 0 Extrapolated To Infinite Time (AUCinf,u) of PF-06835919 | AUCinf,u was defined as unbound area under the plasma concentration time curve from time 0 extrapolated to infinite time. | The PK parameter 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 | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
|
|
|
|
| Primary | Unbound Maximum Plasma Concentration (Cmax,u) of PF-06835919 | Cmax,u was defined as unbound maximum plasma concentration. | The PK parameter 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/mL | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
|
|
|
|
| Primary | Fraction of Drug Unbound (fu) of PF-06835919 | The fraction of PF-06835919 unbound in plasma (fu) was determined at approximately the expected Tmax in each participant. | The PK parameter 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 | ratio | Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1. |
|
|
|
| Secondary | Number of Participants Reporting Treatment-emergent Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AE (TEAE) was defined as an AE with onset date occurring during the on-treatment period. AEs included all SAEs and non-SAEs. | The safety analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Baseline (Day 1) up to follow-up (Day 31) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Change (Chg) From Baseline in Laboratory Tests | To determine if there were any clinically significant laboratory abnormalities, hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular hemoglobin, mean corpuscular volume, platelet count, lymphocytes, neutrophils, activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio), clinical chemistry (bilirubin, direct and indirect bilirubin, gamma glutamyl transferase, albumin, urea nitrogen, glucose) and urinalysis (glucose, protein, hemoglobin, urobilinogen, nitrite) tests were assessed. Each parameter was evaluated against commonly used and widely accepted criteria. | The safety analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Baseline (Day 1) up to Day 6 |
|
|
|
| Secondary | Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiograms (ECGs) | ECG endpoints (PR interval, QRS interval, QT interval and QTcF) meeting the criteria of potential clinical concern were summarized by treatment using categories as defined: 1. PR max. ≥300ms, %Chg ≥25/50%; 3. QRS max. ≥140ms，%Chg ≥50%; 3.maximum post-dose QTcF 450 - ≤480msec, 480 - ≤500msec and >500msec, 30<Chg≤60 and Chg>60. | The safety analysis population was defined as all participants randomly assigned to investigational product and who took at least 1 dose of investigational product. | Posted | Count of Participants | Participants | Baseline (Day 1) up to Day 6 |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Mild Hepatic Impairment | This arm included participants with mild hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Moderate Hepatic Impairment | This arm included participants with moderate hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | Severe Hepatic Impairment | This arm included participants with severe hepatic impairment who received a 25 mg single oral dose of PF-06835919 on Day 1. | 0 | 5 | 0 | 5 | 1 | 5 |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v24.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v24.0 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v24.0 | Non-systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | MedDRA v24.0 | 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.
The effect of the hepatic impairment on PK parameter Cmax were assessed by constructing 90% confidence intervals around the estimated difference between each of the Test (impaired) cohorts and the Reference (without hepatic impairment) cohort using a one-way ANOVA model based on natural log transformed data. |
| Ratio (%) of Adjusted Means |
| 102.24 |
| 2-Sided |
| 90 |
| 74.59 |
| 140.15 |
| Other |
| The effect of the hepatic impairment on PK parameter Cmax were assessed by constructing 90% confidence intervals around the estimated difference between each of the Test (impaired) cohorts and the Reference (without hepatic impairment) cohort using a one-way ANOVA model based on natural log transformed data. | Ratio (%) of Adjusted Means | 83.78 | 2-Sided | 90 | 60.18 | 116.62 | Other |
The effect of the hepatic impairment on PK parameter AUCinf,u were assessed by constructing 90% confidence intervals around the estimated difference between each of the Test (impaired) cohorts and the Reference (without hepatic impairment) cohort using a one-way ANOVA model based on natural log transformed data. |
| Ratio (%) of Adjusted Means |
| 178.50 |
| 2-Sided |
| 90 |
| 129.96 |
| 245.18 |
| Other |
| The effect of the hepatic impairment on PK parameter AUCinf,u were assessed by constructing 90% confidence intervals around the estimated difference between each of the Test (impaired) cohorts and the Reference (without hepatic impairment) cohort using a one-way ANOVA model based on natural log transformed data. | Ratio (%) of Adjusted Means | 195.73 | 2-Sided | 90 | 140.31 | 273.03 | Other |
The effect of the hepatic impairment on PK parameter Cmax,u were assessed by constructing 90% confidence intervals around the estimated difference between each of the Test (impaired) cohorts and the Reference (without hepatic impairment) cohort using a one-way ANOVA model based on natural log transformed data. |
| Ratio (%) of Adjusted Means |
| 136.04 |
| 2-Sided |
| 90 |
| 104.75 |
| 176.67 |
| Other |
| The effect of the hepatic impairment on PK parameter Cmax,u were assessed by constructing 90% confidence intervals around the estimated difference between each of the Test (impaired) cohorts and the Reference (without hepatic impairment) cohort using a one-way ANOVA model based on natural log transformed data. | Ratio (%) of Adjusted Means | 117.87 | 2-Sided | 90 | 89.61 | 155.03 | Other |
| With treatment-related TEAE |
|
| With SAE |
|
|
| Hematocrit (%) <0.8*LLN |
|
|
| Erythrocytes (10^6/mm3) <0.8*LLN |
|
|
| Ery. Mean Corpuscular Volume (um^3) >1.1*upper limit of normal (ULN) |
|
|
| Ery. Mean Corpuscular Hemoglobin (pg/cell) >1.1*ULN |
|
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| Platelets (10^3/mm3) <0.8*LLN |
|
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| Lymphocytes (10^3/mm3) <0.8*LLN |
|
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| Neutrophils (10^3/mm3) <0.8*LLN |
|
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| Activated Partial Thromboplastin Time (sec) >1.1*ULN |
|
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| Prothrombin Time (sec) >1.1*ULN |
|
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| Prothrombin Intl. Normalized Ratio >1.1*ULN |
|
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| Bilirubin (mg/dL) >1.5*ULN |
|
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| Direct Bilirubin (mg/dL) >1.5*ULN |
|
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| Indirect Bilirubin (mg/dL) >1.5*ULN |
|
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| Gamma Glutamyl Transferase (U/L) >3.0*ULN |
|
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| Albumin (g/dL) <0.8*LLN |
|
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| Urea Nitrogen (mg/dL) >1.3*ULN |
|
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| Glucose (mg/dL) >1.5*ULN |
|
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| URINE Glucose (mg/dL) ≥1 |
|
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| URINE Protein (mg/dL) ≥1 |
|
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| URINE Hemoglobin ≥1 |
|
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| Urobilinogen (EU/dL) ≥1 |
|
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| Nitrite ≥1 |
|
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| PR Interval %Chg ≥25/50% |
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| QRS Interval Value ≥140 msec |
|
| QRS Interval %Chg ≥50% |
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| QT Interval Value >500 msec |
|
| QTcF (msec) 450< Value ≤480 |
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| QTcF (msec) 480< Value ≤500 |
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| QTcF (msec) Value >500 |
|
| QTcF (msec) 30< Chg ≤60 |
|
| QTcF (msec) Chg >60 |
|