A Renal Impairment Study for PF-06651600

Phase 1

Terminated

• Conditions: Renal Impairment
• Interventions: Drug: PF-06651600

• Registration Number: NCT04037865
• Lead Sponsor: Pfizer

Brief Summary

This is a Phase 1 non-randomized, open-label, parallel cohort study of PF-06651600 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with mild and moderate renal impairment (Part 2).

Detailed Description

This is a Phase 1 non-randomized, open-label, parallel cohort, multi-site study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-06651600 after multiple oral doses of 50 mg daily. 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 approximately 16 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 with approximately 8 subjects each with moderate and mild renal impairment. The total duration of participation from Screening visit to Day 11 will be a maximum of 39 days and from Screening visit to Follow-up/Contact Visit will a maximum of 73 days.

Study Timeline

• Study First Submitted: 2019-07-26
• Study First Submitted QC: 2019-07-26
• Study First Posted: 2019-07-30
• Study Start: 2019-08-19
• Primary Completion: 2020-03-31
• Study Completion: 2020-03-31
• Results First Submitted: 2021-03-26
• Status Verified: 2021-04
• Results First Submitted QC: 2021-04-27
• Last Update Submitted: 2021-04-27
• Results First Posted: 2021-05-18
• Last Update Posted: 2021-05-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• 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 upon 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
• Mild renal impairment (Part 2 only): eGFR between 60 and 89 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 drug regimen

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Exclusion Criteria

• Females of child-bearing potential must use an accepted, highly effective contraceptive method
• Renal transplant recipients
• Urinary incontinence without catheterization
• Subjects with clinically significant infections within the past 6 months prior to first dose of study drug, evidence of active or chronic infection requiring oral treatment within 4 weeks prior, history of disseminated herpes simplex or recurrent or disseminated herpes zoster
• Subjects with malignancy or with a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of skin or cervical carcinoma in situ
• HIV, Hepatitis B, or Hepatitis C infection

Additional exclusion criteria for subjects with renal impairment:

• Subjects requiring hemodialysis and peritoneal dialysis
• Screening BP >/=180 mmHg (systolic) or >/=110 mmHg (diastolic)
• Screening 12-lead ECG demonstrating QTcF >470 msec

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PF-06651600 Severe Renal Impairment	PF-06651600	This arm includes participants with severe renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10
PF-06651600 Normal Renal Function	PF-06651600	This arm includes participants with normal renal function who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10
PF-06651600 Moderate Renal Impairment	PF-06651600	This arm is in Part 2 which will be conducted if decision criterion to proceed to Part 2 is met. This arm includes participants with moderate renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10
PF-06651600 Mild Renal Impairment	PF-06651600	This arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met. The arm includes participants with mild renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10.

Primary Outcome Measures

Name	Time	Method
Plasma PF-06651600 Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)	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.	Plasma PF-06651600 AUC0-24 was determined using a linear/log trapezoidal method.
Plasma PF-06651600 Maximum Plasma Concentration (Cmax)	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.	The plasma PF-06651600 Cmax was observed directly from data.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria	At screening, on Day -1, Day 11 and early termination/discontinuation.	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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	From Screening (Day -28) through and including up to 35 calendar days after the last administration of investigational product, assessed up to 74 days.	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.
Number of Participants With Laboratory Abnormalities	At Screening Visit 1 and on Days -1, 5, 11 and early termination day.	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.
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria	At screening, on Day 1, Day 5, Day 11 and early termination/discontinuation.	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.

Trial Locations

Locations (3)

Investigational Drug Services (IDS) University of Miami Hospitals and Clinics; 🇺🇸 Miami, Florida, United States

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

Prism Clinical Research, LLC; 🇺🇸 Saint Paul, Minnesota, United States