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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-002865-20 | EudraCT Number |
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This study is a phase 1 non-randomized, open-label, single-dose, parallel-group study of PF 04965842 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with moderate renal impairment (Part 2).
This is a Phase 1 non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-04965842 after a single 200 mg oral dose. Subjects will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: A total of approximately16 subjects will be enrolled; approximately 8 subjects with severe renal impairment and approximately 8 with normal renal function. After statistical evaluation of results from Part 1, Part 2 may be conducted and approximately 8 subjects with moderate renal impairment will be enrolled. The total duration of participation from the Screening Visit to Day 4 will be a maximum of 31 days and from the Screening Visit to Follow-up Contact/Visit will be a maximum of 67 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-04965842 | Experimental | PF 04965842 is an oral selevtive janus kinase (JAK) 1 inhibitor |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-04965842 | Drug | PF 04965842 is a janus kinase (JAK) 1 inhibitor that is currently being developed for the treatment of atopic dermatitis (AD). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) for PF-04965842 | Maximum observed plasma PF-04965842 concentration. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose |
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842 | Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
| Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1) | Maximum observed plasma concentration for active metabolite, PF-06471658 (M1). | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1) | Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1). | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
| Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2) | Maximum observed plasma concentration for active metabolite, PF-07055087 (M2). | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2) | Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Adverse events (AEs): any untoward medical occurrence in a clinical investigation subject administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Causality to study treatment was determined by the investigator. |
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Inclusion Criteria:
Additional inclusion criteria for subjects with renal impairment:
Meet the following eGFR criteria during the screening period based on the MDRD equation:
Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).
Stable concomitant drug regimen.
Exclusion Criteria:
Additional exclusion criteria for subjects with renal impairment:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami Division of Clinical Pharmacology | Miami | Florida | 33136 | United States | ||
| University of Miami, Sylvester Comprehensive Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34637151 | Derived | Wang EQ, Le V, Winton JA, Tripathy S, Raje S, Wang L, Dowty ME, Malhotra BK. Effects of Renal Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites. J Clin Pharmacol. 2022 Apr;62(4):505-519. doi: 10.1002/jcph.1980. Epub 2022 Feb 15. |
| 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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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Renal Function | Participants were selected and categorized into the normal renal function group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula >=90 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
| FG001 | Moderate Renal Impairment | Participants were selected and categorized into the moderate renal impairment group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula >=30 and <60 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
| FG002 | Severe Renal Impairment | Participants were selected and categorized into the severe renal impairment group with the estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) formula <30 mL/min on Day -1 and not requiring dialysis. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Renal Function | Participants were selected and categorized into the normal renal function group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula >=90 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
| 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 | Maximum observed plasma PF-04965842 concentration. | The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose |
|
Baseline up to Follow-Up (Day 36)
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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 | Normal Renal Function | Participants were selected and categorized into the normal renal function group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula >=90 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA v22.1 | 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 |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 30, 2019 | Nov 3, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 10, 2018 | Nov 3, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C000634427 | abrocitinib |
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Part 1 will be conducted. The 8 subjects from the renal impaired group will be recruited before recruiting the 8 subjects without renal impairment function in Part 1. After statistical evaluation of results from Part 1, Part 2 may be conducted.
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| 0 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
| Baseline up to Follow-Up (Day 36) |
| Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria. | Baseline, post-dose on Day 1, Day 2 and Day 4. |
| Number of Participants With Clinically Significant Vital Sign Values | Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator. | Day 1 (pre-dose) and Day 4 |
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values | Clinical significance of ECG data was assessed by the investigator. | Baseline, post-dose on Day 1 and on Day 4 |
| Miami |
| Florida |
| 33136 |
| United States |
| Orlando Clinical Research Center | Orlando | Florida | 32809 | United States |
| Brussels Clinical Research Unit | Brussels | Be-bru | B-1070 | Belgium |
| BG001 |
| Moderate Renal Impairment |
Participants were selected and categorized into the moderate renal impairment group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula >=30 and <60 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
| BG002 | Severe Renal Impairment | Participants were selected and categorized into the severe renal impairment group with the estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) formula <30 mL/min on Day -1 and not requiring dialysis. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
| 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 |
|
| Moderate Renal Impairment |
Participants were selected and categorized into the moderate renal impairment group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula >=30 and <60 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
| OG002 | Severe Renal Impairment | Participants were selected and categorized into the severe renal impairment group with the estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) formula <30 mL/min on Day -1 and not requiring dialysis. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. |
|
|
|
| Primary | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842 | Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time. | The analysis population refers to 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 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
|
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1) | Maximum observed plasma concentration for active metabolite, PF-06471658 (M1). | The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
|
|
|
|
| Primary | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1) | Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1). | The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour/milliliter (ng*hr/mL) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
|
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2) | Maximum observed plasma concentration for active metabolite, PF-07055087 (M2). | The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
|
|
|
|
| Primary | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2) | Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2). | The analysis population refers to 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 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
|
|
|
|
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Adverse events (AEs): any untoward medical occurrence in a clinical investigation subject administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Causality to study treatment was determined by the investigator. | All participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | Baseline up to Follow-Up (Day 36) |
|
|
|
| Secondary | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria. | All participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | Baseline, post-dose on Day 1, Day 2 and Day 4. |
|
|
|
| Secondary | Number of Participants With Clinically Significant Vital Sign Values | Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator. | All participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | Day 1 (pre-dose) and Day 4 |
|
|
|
| Secondary | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values | Clinical significance of ECG data was assessed by the investigator. | All participants who received at least 1 dose of study medication. | Posted | Count of Participants | Participants | Baseline, post-dose on Day 1 and on Day 4 |
|
|
|
| Post-Hoc | Unbound Maximum Observed Plasma Concentration (Cmax,u) of the Active Moiety | The unbound maximum observed plasma concentration for active moiety, calculated as the sum of unbound Cmax for PF-04965842 and active metabolites, PF-06471658 (M1) and PF-07055087 (M2), adjusted for the relative potencies of the metabolites. | The analysis population refers to all participants dosed who had at least 1 of the PK 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, 12, 24, 36, 48 and 72 hours post-dose. |
|
|
|
|
| Post-Hoc | Unbound Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf,u) of the Active Moiety | The unbound area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active moiety, calculated as the sum of unbound AUCinf for PF-04965842 and active metabolites, PF-06471658 (M1) and PF-07055087 (M2), adjusted for the relative potencies of the metabolites. | The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomolar*hour (nM*hr) | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose. |
|
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 1 |
| 8 |
| EG001 | Moderate Renal Impairment | Participants were selected and categorized into the moderate renal impairment group with the estimated glomerular filtration rate (eGRF) based on Modification of Diet in Renal Disease (MDRD) formula >=30 and <60 mL/min on Day -1. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. | 0 | 7 | 0 | 7 | 1 | 7 |
| EG002 | Severe Renal Impairment | Participants were selected and categorized into the severe renal impairment group with the estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) formula <30 mL/min on Day -1 and not requiring dialysis. Participants received a single 200 mg oral dose of PF-04965842 on Day 1 after a fast of at least 10 hours. | 0 | 8 | 0 | 8 | 0 | 8 |
| Toothache | Gastrointestinal disorders | MedDRA v22.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v22.1 | 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.
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
Test: the severe renal impairment group; Reference: the normal renal function group
| ANOVA |
| Ratio of adjusted geometric means |
| 121.32 |
| 2-Sided |
| 90 |
| 68.32 |
| 215.41 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
Test: the severe renal impairment group; Reference: the normal renal function group
| ANOVA |
| Ratio of adjusted geometric means |
| 167.79 |
| 2-Sided |
| 90 |
| 97.20 |
| 289.64 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
Test: the severe renal impairment group; Reference: the normal renal function group
| ANOVA |
| Ratio of adjusted geometric means |
| 287.06 |
| 2-Sided |
| 90 |
| 196.72 |
| 418.89 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
Test: the severe renal impairment group; Reference: the normal renal function group
| ANOVA |
| Ratio of adjusted geometric means |
| 177.92 |
| 2-Sided |
| 90 |
| 135.91 |
| 232.92 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
Test: the severe renal impairment group; Reference: the normal renal function group
| ANOVA |
| Ratio of adjusted geometric means |
| 571.43 |
| 2-Sided |
| 90 |
| 447.27 |
| 730.05 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
| Title | Measurements |
|---|---|
|
Test: the severe renal impairment group; Reference: the normal renal function group
| ANOVA |
| Ratio of adjusted geometric means |
| 129.49 |
| 2-Sided |
| 90 |
| 92.86 |
| 180.57 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |
Test: the severe renal impairment group; Reference: the normal renal function group
| ANOVA |
| Ratio of adjusted geometric means |
| 290.68 |
| 2-Sided |
| 90 |
| 217.39 |
| 388.69 |
| Other |
The ratio and 90% confidence interval were expressed as percentages. |