Clinical trial NCT03660241: A Renal Impairment Study for PF-04965842
Official title: A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-04965842 IN SUBJECTS WITH RENAL IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL RENAL FUNCTION
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-09-06
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Breath alcohol test at Screening and Day -1 must be negative.
* Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m2; and a total body weight \>50 kg (110 lb).

Additional inclusion criteria for subjects with renal impairment:

* Meet the following eGFR criteria during the screening period based on the MDRD equation:

  * Severe renal impairment: eGFR \<30 mL/min, but not requiring hemodialysis.
  * Moderate renal impairment (Part 2 only): eGFR ≥30 mL/min and \<60 mL/min.
* 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:

* Renal transplant recipients.
* Urinary incontinence without catheterization.
* Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), evidence of any infection (including influenza) within the past 7 days prior to baseline, history of disseminated herpes simplex infection or recurrent or disseminated herpes zoster.
* Subjects with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
* History of or current positive results for human immunodeficiency virus, Hepatitis B, Hepatitis C.

Additional exclusion criteria for subjects with renal impairment:

* Subjects requiring hemodialysis and peritoneal dialysis.
* Screening BP ≥ 180 mm Hg (systolic) or ≥ 110 mm Hg (diastolic).
* Screening supine 12-lead ECG demonstrating QTcF \>470 msec or a QRS interval \>120 msec.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for PF-04965842
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
measure: Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
measure: Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
measure: Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
measure: Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)
timeFrame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
measure: Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2)
timeFrame: 0 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Follow-Up (Day 36)
measure: Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline, post-dose on Day 1, Day 2 and Day 4.
measure: Number of Participants With Clinically Significant Vital Sign Values
timeFrame: Day 1 (pre-dose) and Day 4
measure: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values
timeFrame: Baseline, post-dose on Day 1 and on Day 4
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Division of Clinical Pharmacology
state: Florida
city: Miami
country: United States
facility: University of Miami, Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Brussels
country: Belgium
facility: Brussels Clinical Research Unit
state: Be-bru
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.