A Clinical Trial of the Study Medicine (PF-07081532) in People With Diabetes and Kidney Dysfunction

A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY TO EVALUATE THE PHARMACOKINETICS OF PF-07081532 IN ADULT PARTICIPANTS WITH TYPE 2 DIABETES MELLITUS WITH VARYING DEGREES OF RENAL IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT RENAL IMPAIRMENT

The purpose of this study is to understand the effects of kidney functional impairment may have on the study medicine (PF-07081532). People with certain level of kidney functional impairment may process PF-07081532 differently from healthy people. PF-07081532 is developed as a potential treatment for type II diabetes.

Participants will take the study medicine as a tablet by mouth once at the study clinic and then will stay at the study clinic for about 7 days. During that time, the study team will monitor their treatment experience and take some blood samples to test the level of PF-07081532. This will help us understand if certain degree of kidney functional impairment will have an effect on the study medicine PF-07081532.

Study Overview

• Status: Terminated
• Conditions: Renal Impairment; Type 2 Diabetes
• Intervention / Treatment: Drug: PF-07081532

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research, LLC
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research LLC dba Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Stable renal function (for participants not on dialysis) defined as ≤25% difference between 2 measurements of BSA-unnormalized eGFR
2. A prior diagnosis of T2DM with an HbA1c ≥6% and ≤10.5%
3. Women may be of child-bearing potential
4. BMI of 17.5 to 45.4 kg/m2

5. NORMAL FUNCTION (GROUP 1): Normal renal function (mean eGFR ≥90 mL/min) based on an average of measures from Screening visits S1 and S2 (eGFR should be calculated using the 2021 CKD EPI Scr-Scys combined equation:

   • Demographically comparable to participants with impaired renal function at Screening
   • A body weight within ±15 kg of the mean body weight of the pooled renal impairment groups (Groups 2, 3 and 4)
   • An age within ±10 years of the mean age of the pooled renal impairment groups (Groups 2, 3 and 4)
   • Attempts will be made to ensure that the male to female distribution in Group 1 is comparable to that in the pooled renal impairment groups (Groups 2, 3 and 4).

Exclusion Criteria:

1. Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes, or history of diabetic ketoacidosis.
2. History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II-IV heart failure, or transient ischemic attack within 3 months of Screening
3. Personal or family history of MTC or MEN2, or participants with suspected MTC per the investigator's judgement.
4. History of acute pancreatitis within 6 months before Screening or any history of chronic pancreatitis.
5. Urinary incontinence.
6. Participants with acute renal disease.
7. Renal allograft recipients.
8. Participants who have previously received a kidney, liver, or heart transplant.

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: Group 1; Participants without renal impairment will receive a single 20 mg dose of PF 07081532, administered orally	Drug: PF-07081532; One PF-07081532 20 mg tablet, administered orally
Experimental: Group 2; Participants with mild renal impairment will receive a single 20 mg dose of PF 07081532, administered orally	Drug: PF-07081532; One PF-07081532 20 mg tablet, administered orally
Experimental: Group 3; Participants with moderate renal impairment will receive a single 20 mg dose of PF 07081532, administered orally	Drug: PF-07081532; One PF-07081532 20 mg tablet, administered orally
Experimental: Group 4; Participants with severe renal impairment will receive a single 20 mg dose of PF 07081532, administered orally	Drug: PF-07081532; One PF-07081532 20 mg tablet, administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment	Plasma Cmax was observed directly from data.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Unbound Cmax (Cmax,u) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment	Cmax,u was calculated as fu*Cmax. Plasma Cmax was observed directly from data. fu was defined as the fraction of unbound drug in plasma, and was obtained from measurement of protein binding.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment	AUCinf was calculated as AUClast + (Clast*/kel). AUClast was defined as area under the plasma concentration-time profile from time 0 to the time last measurable concentration, and was calculated using linear/log trapezoidal method. Clast* was defined as the predicted plasma concentration at the last quantifiable time point estimated from log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Unbound AUCinf (AUCinf,u) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment	AUCinf,u was calculated as fu*AUCinf. AUCinf was calculated as AUClast + (Clast*/kel). AUClast was defined as area under the plasma concentration-time profile from time 0 to the time last measurable concentration, and was calculated using linear/log trapezoidal method. Clast* was defined as the predicted plasma concentration at the last quantifiable time point estimated from log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. fu was the fraction of unbound drug in plasma, and was obtained from measurement of protein binding.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Unbound Fraction (fu) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment	fu was the ratio of unbound drug concentration to the total drug concentration, and was obtained from measurement of protein binding.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was 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. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent AEs (TEAEs) = AEs occurred after starting of study treatment and up to the end of study that were absent before treatment or that worsened relative to pretreatment state. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related AEs and SAEs were determined by the investigator. Severe=an event that prevents normal everyday activities.	From time of administration of study treatment on Day 1 up to the end of the study (up to a maximum of 31 days post dose)
Number of Participants With Laboratory Test Abnormalities	Parameters analyzed for lab examination included hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin [MCH], MCH concentration, platelet count, white blood cell count, absolute [Abs] total neutrophils, Abs eosinophils, Abs monocytes, Abs basophils, Abs lymphocytes), chemistry (Scr, Scys, fasting plasma glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl eGFR), urinalysis (pH, qualitative [qual] glucose, qual protein, qual blood, ketones, nitrites, leukocyte, esterase, urobilinogen, urine bili, microscopy). Lab parameters meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study are reported. Baseline was defined as the last pre-dose measurement.	Pre-dose, 72 and 144 hours post dose on Day 1
Number of Participants With Vital Signs Data Meeting Pre-Defined Categorical Criteria	Vital signs including single, seated blood pressure (BP) and pulse rate were measured with the participant's arm supported at the level of the heart, and recorded to the nearest mmHg, following a seated rest of ≥5 minutes. Same arm (preferably the dominant arm) was used for BP/pulse rate assessment throughout the study. Vital signs meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study are reported. Baseline was defined as the last pre-dose measurement.	At admission on Day -1, pre-dose, and 24, 72, and 144 hours post the dose on Day 1
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Categorical Criteria	Supine standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) were collected at times specified in the time frame using an ECG machine that automatically calculates the HR and measures PR interval, QT interval, QTcF, and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. ECG data meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study were reported. Baseline was defined as the last pre-dose measurement.	Pre-dose, and 144 hours post the dose on Day 1

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): August 29, 2022
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: August 19, 2022
• First Submitted That Met QC Criteria: August 19, 2022
• First Posted (Actual): August 22, 2022

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; Renal impairment
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Renal Insufficiency
• Other Study ID Numbers: C3991007

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