Trial Outcomes & Findings for A Renal Impairment Study for PF-06651600 (NCT NCT04037865)

Results Overview

The plasma PF-06651600 Cmax was observed directly from data.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

8 participants

Primary outcome timeframe

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.

Results posted on

2021-05-18

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Renal Impairment Study for PF-06651600

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Severe Renal Impairment n=8 Participants 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.
Age, Continuous Mean	59.5 Years STANDARD_DEVIATION 9.78 • n=5 Participants
Age, Customized <18 Years	0 Participants n=5 Participants
Age, Customized 18-44 Years	1 Participants n=5 Participants
Age, Customized 45-64 Years	4 Participants n=5 Participants
Age, Customized >=65 Years	3 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: The analysis population included all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest.

The plasma PF-06651600 Cmax was observed directly from data.

Outcome measures

Outcome measures
Measure	Severe Renal Impairment n=8 Participants 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.
Plasma PF-06651600 Maximum Plasma Concentration (Cmax)	445.6 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 21

PRIMARY outcome

Timeframe: 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.

Population: 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.

Plasma PF-06651600 AUC0-24 was determined using a linear/log trapezoidal method.

Outcome measures

Outcome measures
Measure	Severe Renal Impairment n=8 Participants 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.
Plasma PF-06651600 Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)	986.3 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 33

SECONDARY outcome

Timeframe: From Screening (Day -28) through and including up to 35 calendar days after the last administration of investigational product, assessed up to 74 days.

Population: The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product.

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.

Outcome measures

Outcome measures
Measure	Severe Renal Impairment n=8 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) All-causality TEAEs	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Treatment-related TEAEs	2 Participants

SECONDARY outcome

Timeframe: At Screening Visit 1 and on Days -1, 5, 11 and early termination day.

Population: The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product.

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.

Outcome measures

Outcome measures
Measure	Severe Renal Impairment n=8 Participants 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.
Number of Participants With Laboratory Abnormalities Erythrocytes <0.8xlower limit of normal (LLN)	1 Participants
Number of Participants With Laboratory Abnormalities Erythrocytes mean corpuscular hemoglobin >1.8*upper limit of normal (ULN)	1 Participants
Number of Participants With Laboratory Abnormalities Lymphocytes/leukocytes <0.8*LLN	2 Participants
Number of Participants With Laboratory Abnormalities Eosinophils/leukocytes >1.2*ULN	1 Participants
Number of Participants With Laboratory Abnormalities Blood urea nitrogen >1.3*ULN	8 Participants
Number of Participants With Laboratory Abnormalities Creatine >1.3*ULN	8 Participants
Number of Participants With Laboratory Abnormalities Urate >1.2*ULN	6 Participants
Number of Participants With Laboratory Abnormalities Bicarbonate <0.9*ULN	1 Participants
Number of Participants With Laboratory Abnormalities Glucose >1.5*ULN	1 Participants
Number of Participants With Laboratory Abnormalities Urine glucose >=1	2 Participants
Number of Participants With Laboratory Abnormalities Urine protein >=1	6 Participants
Number of Participants With Laboratory Abnormalities Urine hemoglobin >=1	3 Participants
Number of Participants With Laboratory Abnormalities Leukocyte esterase >=1	2 Participants

SECONDARY outcome

Timeframe: At screening, on Day 1, Day 5, Day 11 and early termination/discontinuation.

Population: The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product.

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.

Outcome measures

Outcome measures
Measure	Severe Renal Impairment n=8 Participants 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.
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria	1 Participants

SECONDARY outcome

Timeframe: At screening, on Day -1, Day 11 and early termination/discontinuation.

Population: The analysis population included all participants assigned to investigational product and who took at least 1 dose of investigational product.

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.

Outcome measures

Outcome measures
Measure	Severe Renal Impairment n=8 Participants 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.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria QRS duration value >= 140 msec	1 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria QTcF interval value >450 msec and <=480 msec	1 Participants

Adverse Events

Severe Renal Impairment

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Total

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Severe Renal Impairment n=8 participants at risk 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.	Total n=8 participants at risk All participants.
Investigations Alanine aminotransferase increased	12.5% 1/8 • 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.	12.5% 1/8 • 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.
Investigations Aspartate aminotransferase increased	12.5% 1/8 • 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.	12.5% 1/8 • 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.
Nervous system disorders Dizziness	12.5% 1/8 • 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.	12.5% 1/8 • 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.
Eye disorders Dry eye	12.5% 1/8 • 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.	12.5% 1/8 • 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.
Musculoskeletal and connective tissue disorders Pain in extremity	12.5% 1/8 • 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.	12.5% 1/8 • 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 1/8 • 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.	12.5% 1/8 • 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.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 18007181021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER