A Renal Impairment Study for PF-06651600

A PHASE 1, NON-RANDOMIZED, OPEN LABEL, MULTIPLE DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF 06651600 IN PARTICIPANTS WITH RENAL IMPAIRMENT AND IN HEALTHY PARTICIPANTS WITH NORMAL RENAL FUNCTION

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).

Study Overview

• Status: Terminated
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: PF-06651600

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Division of Clinical Pharmacology
    • Miami, Florida, United States, 33136
      • Investigational Drug Services (IDS) University of Miami Hospitals and Clinics
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06651600 Severe Renal Impairment; This arm includes participants with severe renal impairment who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10	Drug: PF-06651600; PF-06651600 50 mg oral tablets will be administered on Days 1 to 10
Experimental: PF-06651600 Normal Renal Function; This arm includes participants with normal renal function who will receive oral doses of PF-06651600 50 mg on Day 1 through Day 10	Drug: PF-06651600; PF-06651600 50 mg oral tablets will be administered on Days 1 to 10
Experimental: PF-06651600 Moderate Renal Impairment; 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	Drug: PF-06651600; PF-06651600 50 mg oral tablets will be administered on Days 1 to 10
Experimental: PF-06651600 Mild Renal Impairment; 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.	Drug: PF-06651600; PF-06651600 50 mg oral tablets will be administered on Days 1 to 10

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2019
• Primary Completion (Actual): March 31, 2020
• Study Completion (Actual): March 31, 2020

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: B7981020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No