A Renal Impairment Study for PF-04965842

Phase 1

Completed

• Conditions: Renal Impairment
• Interventions: Drug: PF-04965842

• Registration Number: NCT03660241
• Lead Sponsor: Pfizer

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.

Study Timeline

• Study First Submitted: 2018-09-04
• Study First Submitted QC: 2018-09-04
• Study First Posted: 2018-09-06
• Study Start: 2018-10-05
• Primary Completion: 2019-11-05
• Study Completion: 2019-11-05
• Results First Submitted: 2020-11-03
• Results First Submitted QC: 2020-12-15
• Results First Posted: 2020-12-17
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-21
• Last Update Posted: 2022-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PF-04965842	PF-04965842	PF 04965842 is an oral selevtive janus kinase (JAK) 1 inhibitor

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) for PF-04965842	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.
Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1)	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).
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1)	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).
Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)	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).
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2)	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).
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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 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.
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	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.
Number of Participants With Clinically Significant Vital Sign Values	Day 1 (pre-dose) and Day 4	Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values	Baseline, post-dose on Day 1 and on Day 4	Clinical significance of ECG data was assessed by the investigator.

Trial Locations

Locations (4)

University of Miami, Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

University of Miami Division of Clinical Pharmacology; 🇺🇸 Miami, Florida, United States

Brussels Clinical Research Unit; 🇧🇪 Brussels, Be-bru, Belgium