Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a Phase 1 non randomized, open label, single dose, parallel cohort study to investigate the effect of hepatic impairment on the PK, safety and tolerability of PF 04965842.
A minimum of 24 subjects with normal, mild or moderate hepatic function will be enrolled into the study, with approximately 8 subjects in each cohort. The Child Pugh classification score will be utilized to assess entry criteria and to assign subjects into the appropriate hepatic impairment group. For individual subjects, the total maximum duration of study participation from the Screening visit to the end of clinical research unit (CRU) stay is approximately 31 days and approximately 63 days from the Screening visit to the Follow up contact.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-04965842 | Experimental | PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-04965842 | Drug | PF 04965842 is an orally bioavailable small molecule that selectively inhibits JAK1. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) for PF-04965842 | Cmax is maximum plasma concentration. It was observed directly from data. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842 | AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842 | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent adverse events (TEAEs) were those with initial onset or increasing in severity between the first dose of investigational product and up to 36 days post-dose. | From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants. |
Not provided
Inclusion Criteria:
Additional Inclusion Criteria for subjects with hepatic impairment:
Exclusion Criteria:
Additional exclusion criteria for subjects with hepatic impairment:
Not provided
Not provided
Not provided
Not provided
Not provided
| 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 | ||
| Prism Clinical Research, LLC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35061234 | Derived | Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21. | |
| 33749838 | Derived | Wang EQ, Le V, O'Gorman M, Tripathy S, Dowty ME, Wang L, Malhotra BK. Effects of Hepatic Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites. J Clin Pharmacol. 2021 Oct;61(10):1311-1323. doi: 10.1002/jcph.1858. Epub 2021 Apr 17. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | PF-04965842 (Normal Hepatic Function Cohort) | Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
| FG001 | PF-04965842 (Mild Hepatic Impairment Cohort) | Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
| FG002 | PF-04965842 (Moderate Hepatic Impairment Cohort) | Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The baseline analysis population included all participants enrolled in the study.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | PF-04965842 (Normal Hepatic Function Cohort) | Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
| BG001 | PF-04965842 (Mild Hepatic Impairment Cohort) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 Observed Plasma Concentration (Cmax) for PF-04965842 | Cmax is maximum plasma concentration. It was observed directly from data. | The pharmacokinetic concentration population was defined as all participants who received 1 dose of PF-04965842 and in whom at least 1 plasma concentration value was reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort |
|
From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-04965842 (Normal Hepatic Function Cohort) | Participants with normal hepatic function were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA v22.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 23, 2018 | Apr 28, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 22, 2018 | Apr 28, 2020 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C000634427 | abrocitinib |
Not provided
Not provided
Not provided
Recruitment for subjects with moderate and mild hepatic impairment (Cohorts 1 and 2) will initiate first and these subjects will be enrolled in parallel.
Not provided
Not provided
Not provided
Not provided
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Laboratory tests included tests that were performed under the categories of hematology, chemistry, urinalysis, other, and additional tests needed for Hy's law. | Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose. |
| Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842 | 12-Lead ECGs were collected after the participants rested quietly for at least 10 minutes in a supine position. Clinical significance of ECG recordings was determined at the investigator's discretion. | Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose. |
| Number of Participants With Vital Sign Findings of Potential Clinical Importance for PF-04965842 | Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant following at least 5 minutes of supine rest. Clinical significance of vital signs was determined at the investigator's discretion. | Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose. |
| Saint Paul |
| Minnesota |
| 55114 |
| United States |
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
| BG002 | PF-04965842 (Moderate Hepatic Impairment Cohort) | Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
| OG002 | PF-04965842 (Moderate Hepatic Impairment Cohort) | Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-04965842 | AUCinf is area under the concentration-time curve (AUC) from time 0 (pre-dose) extrapolated to infinite time. | The pharmacokinetic parameter analysis population was defined as all participants dosed who had at least 1 of the pharmocokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort |
|
|
|
|
| Post-Hoc | Unbound Cmax (Cmax,u) for Active Moiety | Cmax,u is unbound Cmax. The active moiety is comprised of parent drug PF-04965842, active metabolites PF-06471658 and PF-07055087. | The pharmacokinetic parameter analysis population was defined as all participants dosed who had at least 1 of the pharmocokinetic parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomolar (nM) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort |
|
|
|
|
| Post-Hoc | Unbound AUCinf (AUCinf,u) for Active Moiety | AUCinf,u is unbound AUCinf. The active moiety is comprised of parent drug PF-04965842, active metabolites PF-06471658 and PF-07055087. | The analysis population was defined as all participants contributing to the summary statistics for AUCinf,u. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomolar*hour (nM*hr) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72 hours post-dose in each cohort |
|
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (AEs) for PF-04965842 | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent adverse events (TEAEs) were those with initial onset or increasing in severity between the first dose of investigational product and up to 36 days post-dose. | All participants who received PF-04965842 were included in the safety analyses. | Posted | Number | Participants | From screening (within 28 days prior to Day 1) till up to 36 days post-dose, the total maximum duration was approximately 63 days for individual participants. |
|
|
|
| Secondary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Laboratory tests included tests that were performed under the categories of hematology, chemistry, urinalysis, other, and additional tests needed for Hy's law. | All participants who received PF-04965842 were included in the safety analyses. | Posted | Number | Participants | Screening (within 28 days prior to Day 1), Day -1, 2, 24, 72 hours post-dose. |
|
|
|
| Secondary | Number of Participants With Electrocardiogram (ECG) Findings of Potential Clinical Importance for PF-04965842 | 12-Lead ECGs were collected after the participants rested quietly for at least 10 minutes in a supine position. Clinical significance of ECG recordings was determined at the investigator's discretion. | All participants who received PF-04965842 were included in the safety analyses. | Posted | Number | Participants | Screening (within 28 days prior to Day 1), Day -1, 2, 72 hours post-dose. |
|
|
|
| Secondary | Number of Participants With Vital Sign Findings of Potential Clinical Importance for PF-04965842 | Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant following at least 5 minutes of supine rest. Clinical significance of vital signs was determined at the investigator's discretion. | All participants who received PF-04965842 were included in the safety analyses. | Posted | Number | Participants | Screening (within 28 days prior to Day 1), 0 (pre-dose), and 72 hours post-dose. |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 2 |
| 8 |
| EG001 | PF-04965842 (Mild Hepatic Impairment Cohort) | Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. | 0 | 8 | 0 | 8 | 3 | 8 |
| EG002 | PF-04965842 (Moderate Hepatic Impairment Cohort) | Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received a single oral dose of PF-04965842 200 mg. | 0 | 8 | 0 | 8 | 0 | 8 |
| Nausea | Gastrointestinal disorders | MedDRA v22.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA v22.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v22.0 | 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.
Moderate Hepatic Impairment (Test) versus Normal Hepatic Function (Reference)
| ANOVA |
| Ratio of Adjusted Geometric Mean |
| 153.99 |
| 2-Sided |
| 90 |
| 99.52 |
| 238.25 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
Moderate Hepatic Impairment (Test) versus Normal Hepatic Function (Reference)
| ANOVA |
| Ratio of Adjusted Geometric Means |
| 84.14 |
| 2-Sided |
| 90 |
| 63.59 |
| 111.33 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
Moderate Hepatic Impairment (Test) versus Normal Hepatic Function (Reference)
| ANOVA |
| Ratio of Adjusted Geometric Means |
| 114.82 |
| 2-Sided |
| 90 |
| 87.19 |
| 151.20 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
|