NCT03660241

A Renal Impairment Study for PF-04965842

Completed Phase 1 Results posted Last updated 22 March 2022

What this trial tests

Phase 1 trial testing PF-04965842 in Renal Impairment in 23 participants. Completed in 5 November 2019.

Timeline

5 October 2018

Primary endpoint
5 November 2019

5 November 2019

Quick facts

Lead sponsor	Pfizer
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	23
Start date	5 October 2018
Primary completion	5 November 2019
Estimated completion	5 November 2019
Sites	4 locations across Belgium, United States

Drugs / interventions tested

• PF-04965842 — full drug profile →

Conditions studied

• Renal Impairment — all drugs for Renal Impairment →

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 75, any sex, with Renal Impairment. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Observed Plasma Concentration (Cmax) for PF-04965842 Primary · 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose

Maximum observed plasma PF-04965842 concentration.

Group	Value	95% CI
Normal Renal Function	1174	± 56
Moderate Renal Impairment	1626	± 31
Severe Renal Impairment	1164	± 80

Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842 Primary · 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 PF-04965842 concentration-time profile from time 0 extrapolated to infinite time.

Group	Value	95% CI
Normal Renal Function	4827	± 65
Moderate Renal Impairment	8828	± 37
Severe Renal Impairment	5855	± 73

Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1) Primary · 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 for active metabolite, PF-06471658 (M1).

Group	Value	95% CI
Normal Renal Function	193.7	± 54
Moderate Renal Impairment	192.8	± 65
Severe Renal Impairment	325.0	± 81

Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1) Primary · 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 for active metabolite, PF-06471658 (M1).

Group	Value	95% CI
Normal Renal Function	872.6	± 44
Moderate Renal Impairment	1346	± 43
Severe Renal Impairment	2505	± 45

Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2) Primary · 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 for active metabolite, PF-07055087 (M2).

Group	Value	95% CI
Normal Renal Function	241.3	± 34
Moderate Renal Impairment	331.6	± 21
Severe Renal Impairment	429.3	± 28

Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2) Primary · 0 (pre-dose), and at 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 for active metabolite, PF-07055087 (M2).

Group	Value	95% CI
Normal Renal Function	1476	± 31
Moderate Renal Impairment	3981	± 38
Severe Renal Impairment	8433	± 25

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Secondary · Baseline up to Follow-Up (Day 36)

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

All-causality

Group	Value	95% CI
Normal Renal Function	1
Moderate Renal Impairment	1
Severe Renal Impairment	0

Treatment-related

Group	Value	95% CI
Normal Renal Function	0
Moderate Renal Impairment	1
Severe Renal Impairment	0

Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) Secondary · Baseline, post-dose on Day 1, Day 2 and Day 4.

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.

Group	Value	95% CI
Normal Renal Function	6
Moderate Renal Impairment	6
Severe Renal Impairment	8

Number of Participants With Clinically Significant Vital Sign Values Secondary · Day 1 (pre-dose) and Day 4

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

Group	Value	95% CI
Normal Renal Function	0
Moderate Renal Impairment	0
Severe Renal Impairment	0

Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values Secondary · Baseline, post-dose on Day 1 and on Day 4

Clinical significance of ECG data was assessed by the investigator.

Group	Value	95% CI
Normal Renal Function	0
Moderate Renal Impairment	0
Severe Renal Impairment	0

Unbound Maximum Observed Plasma Concentration (Cmax,u) of the Active Moiety Secondary · 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

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.

Group	Value	95% CI
Normal Renal Function	2099	± 38
Moderate Renal Impairment	2810	± 20
Severe Renal Impairment	2718	± 41

Unbound Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf,u) of the Active Moiety Secondary · 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.

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.

Group	Value	95% CI
Normal Renal Function	9955	± 40
Moderate Renal Impairment	20920	± 28
Severe Renal Impairment	28940	± 23

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Follow-Up (Day 36). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Normal Renal Function

Serious: 0/8 (0%)

Deaths: 0/8

Moderate Renal Impairment

Serious: 0/7 (0%)

Deaths: 0/7

Severe Renal Impairment

Serious: 0/8 (0%)

Deaths: 0/8

Other adverse events (3 terms — click to expand)

Reaction	System	Normal Renal Function	Moderate Renal Impairment	Severe Renal Impairment
Nausea	Gastrointestinal disorders	—	—	—
Toothache	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—

Data from ClinicalTrials.gov NCT03660241 adverse events section.

Sponsor's own description

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).

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effects of Renal Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites.
   Wang EQ, Le V, Winton JA, Tripathy S, et al · · 2022 · cited 18× · PMID 34637151 · DOI 10.1002/jcph.1980
2. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis.
   Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, et al · · 2022 · cited 16× · PMID 35061234 · DOI 10.1007/s40262-021-01104-z