Trial Outcomes & Findings for A Renal Impairment Study for PF-04965842 (NCT NCT03660241)

Results Overview

Maximum observed plasma PF-04965842 concentration.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

23 participants

Primary outcome timeframe

0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose

Results posted on

2022-03-22

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	8	7	8
Overall Study COMPLETED	8	7	8
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Renal Impairment Study for PF-04965842

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.	Total n=23 Participants Total of all reporting groups
Age, Continuous	59.8 Years STANDARD_DEVIATION 4.71 • n=5 Participants	65.7 Years STANDARD_DEVIATION 8.34 • n=7 Participants	61.0 Years STANDARD_DEVIATION 14.46 • n=5 Participants	62.0 Years STANDARD_DEVIATION 9.96 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	16 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	19 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose

Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.

Maximum observed plasma PF-04965842 concentration.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Maximum Observed Plasma Concentration (Cmax) for PF-04965842	1174 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 56	1626 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 31	1164 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 80

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.

Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=7 Participants 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.
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842	4827 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 65	8828 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 37	5855 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 73

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.

Maximum observed plasma concentration for active metabolite, PF-06471658 (M1).

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1)	193.7 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 54	192.8 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 65	325.0 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 81

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.

Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1).

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1)	872.6 nanogramhour/milliliter (nghr/mL) Geometric Coefficient of Variation 44	1346 nanogramhour/milliliter (nghr/mL) Geometric Coefficient of Variation 43	2505 nanogramhour/milliliter (nghr/mL) Geometric Coefficient of Variation 45

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.

Maximum observed plasma concentration for active metabolite, PF-07055087 (M2).

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)	241.3 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 34	331.6 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 21	429.3 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 28

PRIMARY outcome

Timeframe: 0 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.

Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2).

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2)	1476 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 31	3981 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 38	8433 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 25

SECONDARY outcome

Timeframe: Baseline up to Follow-Up (Day 36)

Population: All participants who received at least 1 dose of study medication.

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.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) All-causality	1 Participants	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, post-dose on Day 1, Day 2 and Day 4.

Population: All participants who received at least 1 dose of study medication.

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.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	6 Participants	6 Participants	8 Participants

SECONDARY outcome

Timeframe: Day 1 (pre-dose) and Day 4

Population: All participants who received at least 1 dose of study medication.

Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Number of Participants With Clinically Significant Vital Sign Values	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, post-dose on Day 1 and on Day 4

Population: All participants who received at least 1 dose of study medication.

Clinical significance of ECG data was assessed by the investigator.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values	0 Participants	0 Participants	0 Participants

POST_HOC outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.

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.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=8 Participants 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.
Unbound Maximum Observed Plasma Concentration (Cmax,u) of the Active Moiety	2099 nanomolar (nM) Geometric Coefficient of Variation 38	2810 nanomolar (nM) Geometric Coefficient of Variation 20	2718 nanomolar (nM) Geometric Coefficient of Variation 41

POST_HOC outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

Population: The analysis population refers to all participants dosed who had at least 1 of the PK parameters of primary interest.

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.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=8 Participants 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.	Moderate Renal Impairment n=7 Participants 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.	Severe Renal Impairment n=7 Participants 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.
Unbound Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf,u) of the Active Moiety	9955 nanomolarhour (nMhr) Geometric Coefficient of Variation 40	20920 nanomolarhour (nMhr) Geometric Coefficient of Variation 28	28940 nanomolarhour (nMhr) Geometric Coefficient of Variation 23

Adverse Events

Normal Renal Function

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Moderate Renal Impairment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Severe Renal Impairment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Normal Renal Function n=8 participants at risk 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.	Moderate Renal Impairment n=7 participants at risk 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.	Severe Renal Impairment n=8 participants at risk 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.
Gastrointestinal disorders Nausea	0.00% 0/8 • Baseline up to Follow-Up (Day 36)	14.3% 1/7 • Baseline up to Follow-Up (Day 36)	0.00% 0/8 • Baseline up to Follow-Up (Day 36)
Gastrointestinal disorders Toothache	12.5% 1/8 • Baseline up to Follow-Up (Day 36)	14.3% 1/7 • Baseline up to Follow-Up (Day 36)	0.00% 0/8 • Baseline up to Follow-Up (Day 36)
Nervous system disorders Headache	0.00% 0/8 • Baseline up to Follow-Up (Day 36)	14.3% 1/7 • Baseline up to Follow-Up (Day 36)	0.00% 0/8 • Baseline up to Follow-Up (Day 36)

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

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