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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
18
One PF-07081532 20 mg tablet, administered orally
Genesis Clinical Research, LLC
Tampa, Florida, United States
Prism Research LLC dba Nucleus Network
Saint Paul, Minnesota, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
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.
Time frame: 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.
Time frame: 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.
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Time frame: 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.
Time frame: Pre-dose, and 144 hours post the dose on Day 1