Renal Impairment Study of PF-06700841

A PHASE 1, NON-RANDOMIZED, OPEN LABEL, SINGLE DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-06700841 IN PARTICIPANTS WITH RENAL IMPAIRMENT AND IN HEALTHY PARTICIPANTS WITH NORMAL RENAL FUNCTION

The purpose of this study is to characterize the effect of kidney impairment on the blood concentrations of PF-06700841 and its major metabolite. Findings from this study will be used to develop dosing recommendations so that the dose and/or dosing interval may be adjusted appropriately in the presence of kidney disease.

Study Overview

• Status: Completed
• Conditions: Renal Impairment; Healthy Volunteer
• Intervention / Treatment: Drug: PF-06700841

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-06700841 after a single oral dose of 30 mg. 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 4 will be a maximum of 32 days and from Screening visit to Follow-up/Contact Visit will a maximum of 67 days.

• Study Type: Interventional
• Enrollment (Actual): 30
• 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, Research Pharmacy
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research LLC dba Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female participants who are between the ages of 18 and 75 years, inclusive, at the Screening visit.
• Body mass index (BMI) of ≥17.5 to ≤40 kg/m2; and a total body weight >50 kg.
• Normal, Severe, Moderate and Mild renal function at 2 Screening visits.
• Stable drug regimen

Exclusion Criteria:

• 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 to first dose
• Known history of pulmonary embolism or recurrent deep vein thrombosis
• Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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-06700841 Severe Renal Impairment; This arm includes participants with severe renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1	Drug: PF-06700841; A single dose of 30 mg PF-06700841 will be administered on Day 1
Experimental: PF-06700841 Normal Renal Function; This arm includes participants with normal renal function who will receive a single oral dose of 30 mg PF-06700841 on Day 1	Drug: PF-06700841; A single dose of 30 mg PF-06700841 will be administered on Day 1
Experimental: PF-06700841 Moderate Renal Impairment; This arm includes participants with moderate renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1	Drug: PF-06700841; A single dose of 30 mg PF-06700841 will be administered on Day 1
Experimental: PF-06700841 Mild Renal Impairment; This arm includes participants with mild renal impairment who will receive a single oral dose of 30 mg PF-06700841 on Day 1	Drug: PF-06700841; A single dose of 30 mg PF-06700841 will be administered on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function	Cmax is the maximum observed plasma concentration of PF-06700841 within 72 hours post dose, which was observed directly from the plasma concentration-time data.	Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose
Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of PF-06700841 Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function	AUCinf was area under the concentration-time curve from time 0 to infinity, which was calculated for PF-06700841 from the concentration-time data.	Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose
Cmax of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function	Cmax is the maximum observed plasma concentration of PF-06802530 (M1), a major metabolite of PF-06700841 within 72 hours post dose, which was observed directly from the plasma concentration-time data.	Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose
AUCinf of PF-06802530 (M1) Following Single Oral Dose Administration in Participants With Renal Impairment and in Healthy Participants With Normal Renal Function	AUCinf was area under the concentration-time curve from time 0 to infinity, which was calculated for PF-06802530 (M1), a major metabolite of PF-06700841 from the concentration-time data.	Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours after dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Any events occurring following start of treatment or increasing in severity after the start of the treatment were counted as treatment emergent. An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect. Severe adverse events is an event that prevents normal everyday activities which is a category utilized for rating the intensity of an event.	From screening (Day-28 to Day -2) to up to 35 days after the study treatment (for a period of up to 63 days)
Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality	The hematology, clinical chemistry and urinalysis abnormalities were summarized in accordance with the sponsor reporting standards without regard to baseline abnormality. Baseline is defined as the last planned predose measurement taken on Day -1.	Baseline (Day -1) and Day 4
Number of Participants With Post-baseline Vital Sign Abnormalities	Vital Signs were assessed against the criteria specified in the sponsor reporting standards for potential clinical concerns. Vital sign abnormalities criteria included: 1) Systolic blood pressure (BP) in millimeters of mercury (mmHg): <90 mmHg with increase or decrease from baseline of ≥30 mmHg with high and low post baseline values; 2) Diastolic blood pressure (BP) (mmHg): <50 mmHg with increase or decrease from baseline of ≥20 mmHg with high and low post baseline values; 3) Supine pulse rate in beats per minutes (bpm): >120 or <40 bpm. Categories with at least 1 participant having vital sign abnormality in any of the reporting arms, were reported in this outcome measure. Baseline is defined as the last planned predose measurement taken on Day 1.	Baseline (Day 1) and Day 4
Number of Participants With Post-baseline Electrocardiogram (ECG) Abnormalities	ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): > 450, >480, >500, increase from baseline >30, increase from baseline >60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60. Categories with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure. Baseline is defined as the last planned predose measurement taken on Day 1.	0 hr pre-dose and 1-, 3-, and 6-hours post-dose on Day 1; Day 4

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, 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): July 3, 2020
• Primary Completion (Actual): May 4, 2022
• Study Completion (Actual): May 4, 2022

Study Registration Dates

• First Submitted: February 5, 2020
• First Submitted That Met QC Criteria: February 5, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; PF-06700841
• Other Study ID Numbers: B7931048

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