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The study was terminated due to extensive Covid-19 delay.
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This is a Phase 1 non-randomized, open-label, parallel cohort study of PF-06651600 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with mild and moderate renal impairment (Part 2).
This is a Phase 1 non-randomized, open-label, parallel cohort, multi-site study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-06651600 after multiple oral doses of 50 mg daily. 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 approximately 16 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 with approximately 8 subjects each with moderate and mild renal impairment. The total duration of participation from Screening visit to Day 11 will be a maximum of 39 days and from Screening visit to Follow-up/Contact Visit will a maximum of 73 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-06651600 Severe Renal Impairment | Experimental | This arm includes participants with severe renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10 |
|
| PF-06651600 Normal Renal Function | Experimental | This arm includes participants with normal renal function who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10 |
|
| PF-06651600 Moderate Renal Impairment | Experimental | This arm is in Part 2 which will be conducted if decision criterion to proceed to Part 2 is met. This arm includes participants with moderate renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10 |
|
| PF-06651600 Mild Renal Impairment | Experimental | This arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met. The arm includes participants with mild renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-06651600 | Drug | PF-06651600 50 mg oral tablets will be administered on Days 1 to 10 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma PF-06651600 Maximum Plasma Concentration (Cmax) | The plasma PF-06651600 Cmax was observed directly from data. | On Day 8 and Day 9 predose, and at 0 (predose), 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16 hours after dose on Day 10, and 24 hours after dose on Day 11. |
| Plasma PF-06651600 Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) | Plasma PF-06651600 AUC0-24 was determined using a linear/log trapezoidal method. | On Day 8 and Day 9 predose, and at 0 (predose), 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16 hours after dose on Day 10, and 24 hours after dose on Day 11. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE is considered a TEAE is the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs. An AE was considered treatment-related if the causality of the AE was assessed to be the investigational product. The causality of AEs was assessed by the investigator using clinical judgment. |
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Inclusion Criteria:
Additional inclusion criteria for subjects with renal impairment:
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 |
|---|---|---|---|---|---|---|
| Investigational Drug Services (IDS) University of Miami Hospitals and Clinics | Miami | Florida | 33136 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37917289 | Derived | Wojciechowski J, S Purohit V, Huh Y, Banfield C, Nicholas T. Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development. Clin Pharmacokinet. 2023 Dec;62(12):1765-1779. doi: 10.1007/s40262-023-01318-3. Epub 2023 Nov 2. | |
| 36977960 | Derived | Purohit V, Huh Y, Wojciechowski J, Plotka A, Salts S, Antinew J, Dimitrova A, Nicholas T. Leveraging Prior Healthy Participant Pharmacokinetic Data to Evaluate the Impact of Renal and Hepatic Impairment on Ritlecitinib Pharmacokinetics. AAPS J. 2023 Mar 28;25(3):32. doi: 10.1208/s12248-023-00792-8. |
| 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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The study was terminated, only participants with severe renal impairment were enrolled. Therefore, in this study, data were collected only for participants with severe renal impairment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Severe Renal Impairment | Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The baseline analysis population included all participants enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Severe Renal Impairment | Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease. |
| 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 | Plasma PF-06651600 Maximum Plasma Concentration (Cmax) | The plasma PF-06651600 Cmax was observed directly from data. | The analysis population included all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | On Day 8 and Day 9 predose, and at 0 (predose), 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16 hours after dose on Day 10, and 24 hours after dose on Day 11. |
|
From Screening (Day -28) through and including up to 35 calendar days after the last administration of investigational product, assessed up to 74 days.
Serious adverse events (SAEs) and non-serious AEs were recorded on the CRF. SAEs were also reported on the Clinical Trial (CT) SAE report form to Pfizer Safety within 24 hours of awareness.
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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 | Severe Renal Impairment | Participants with severe renal impairment were included to receive oral PF-06651600 50 mg daily for up to 10 days from Day 1 to Day 10. Stages of renal impairment were based on Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
Since the study was terminated, the results of this study was not complete and the interpretation of the study results was limited.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 18007181021 | 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 | May 10, 2019 | Mar 26, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 1, 2019 | Mar 26, 2021 | 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 |
|---|---|
| C000614924 | PF-06651600 |
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| From Screening (Day -28) through and including up to 35 calendar days after the last administration of investigational product, assessed up to 74 days. |
| Number of Participants With Laboratory Abnormalities | Safety laboratory assessments include clinical chemistry, hematology and urinalysis. Serum creatinine was only assessed on Screening visit 2 and on Day 2 and Day 8 for eGFR assessment. The number of participants with laboratory test abnormalities without regard to baseline abnormality was reported. | At Screening Visit 1 and on Days -1, 5, 11 and early termination day. |
| Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Vital signs evaluations included supine blood pressure (BP), pulse rate, and temperature. Criteria for vital signs values included: supine diastolic BP >= 20 mmHg increase from baseline, supine systolic BP >= 30 mmHg increase from baseline, supine diastolic BP >= 20 mmHg decrease from baseline, and supine systolic BP >= 30 mmHg decrease from baseline. | At screening, on Day 1, Day 5, Day 11 and early termination/discontinuation. |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | ECG criteria included PR, QT, and QTc intervals and QRS complex. Participants with absolute data value meeting the following criteria were reported: aggregate PR interval value >= 300 msec, aggregate QRS duration value >= 140 msec, absolute QTcF interval value >450 msec and <= 480 msec, or >480 msec and <=500 msec, or >500 msec. | At screening, on Day -1, Day 11 and early termination/discontinuation. |
| University of Miami Division of Clinical Pharmacology |
| Miami |
| Florida |
| 33136 |
| United States |
| Prism Clinical Research, LLC | Saint Paul | Minnesota | 55114 | United States |
| Years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
|
|
| Primary | Plasma PF-06651600 Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) | Plasma PF-06651600 AUC0-24 was determined using a linear/log trapezoidal method. | The analysis population included all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | On Day 8 and Day 9 predose, and at 0 (predose), 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16 hours after dose on Day 10, and 24 hours after dose on Day 11. |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE is considered a TEAE is the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the last dose plus the lag time were flagged as TEAEs. An AE was considered treatment-related if the causality of the AE was assessed to be the investigational product. The causality of AEs was assessed by the investigator using clinical judgment. | The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product. | Posted | Count of Participants | Participants | From Screening (Day -28) through and including up to 35 calendar days after the last administration of investigational product, assessed up to 74 days. |
|
|
|
| Secondary | Number of Participants With Laboratory Abnormalities | Safety laboratory assessments include clinical chemistry, hematology and urinalysis. Serum creatinine was only assessed on Screening visit 2 and on Day 2 and Day 8 for eGFR assessment. The number of participants with laboratory test abnormalities without regard to baseline abnormality was reported. | The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product. | Posted | Count of Participants | Participants | At Screening Visit 1 and on Days -1, 5, 11 and early termination day. |
|
|
|
| Secondary | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Vital signs evaluations included supine blood pressure (BP), pulse rate, and temperature. Criteria for vital signs values included: supine diastolic BP >= 20 mmHg increase from baseline, supine systolic BP >= 30 mmHg increase from baseline, supine diastolic BP >= 20 mmHg decrease from baseline, and supine systolic BP >= 30 mmHg decrease from baseline. | The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product. | Posted | Count of Participants | Participants | At screening, on Day 1, Day 5, Day 11 and early termination/discontinuation. |
|
|
|
| Secondary | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | ECG criteria included PR, QT, and QTc intervals and QRS complex. Participants with absolute data value meeting the following criteria were reported: aggregate PR interval value >= 300 msec, aggregate QRS duration value >= 140 msec, absolute QTcF interval value >450 msec and <= 480 msec, or >480 msec and <=500 msec, or >500 msec. | The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product. | Posted | Count of Participants | Participants | At screening, on Day -1, Day 11 and early termination/discontinuation. |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 3 |
| 8 |
| EG001 | Total | All participants. | 0 | 8 | 0 | 8 | 3 | 8 |
| Aspartate aminotransferase increased | Investigations | MedDRA v23.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA v23.1 | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA v23.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | 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 |
|
| Eosinophils/leukocytes >1.2*ULN |
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| Blood urea nitrogen >1.3*ULN |
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| Creatine >1.3*ULN |
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| Urate >1.2*ULN |
|
| Bicarbonate <0.9*ULN |
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| Glucose >1.5*ULN |
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| Urine glucose >=1 |
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| Urine protein >=1 |
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| Urine hemoglobin >=1 |
|
| Leukocyte esterase >=1 |
|