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

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05510245

Enrollment

Registered

2022-08-22

Start date

2022-08-29

Completion date

2023-07-20

Last updated

2024-11-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Renal Impairment, Type 2 Diabetes

Keywords

Type 2 Diabetes, Renal impairment

Brief summary

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.

Interventions

DRUGPF-07081532

One PF-07081532 20 mg tablet, administered orally

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Unbound Fraction (fu) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment	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	fu was the ratio of unbound drug concentration to the total drug concentration, and was obtained from measurement of protein binding.
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	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	Plasma Cmax was observed directly from data.
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	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	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.
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	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	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.
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	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	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.

Secondary

Measure	Time frame	Description
Number of Participants With Laboratory Test Abnormalities	Pre-dose, 72 and 144 hours post dose on Day 1	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.
Number of Participants With Vital Signs Data Meeting Pre-Defined Categorical Criteria	At admission on Day -1, pre-dose, and 24, 72, and 144 hours post the dose on Day 1	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.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Categorical Criteria	Pre-dose, and 144 hours post the dose on Day 1	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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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)	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.

Countries

United States

Participant flow

Recruitment details

The study was terminated due to the termination of clinical development of PF-07081532. As of the last participant last visit (LPLV) date (20 Jul 2023), a total of 18 participants were enrolled at 2 sites in the United States, and no participants without renal impairment were enrolled due to early study termination.

Participants by arm

Arm	Count
Mild Renal Impairment Participants with mild renal impairment received a single dose of PF-07081532 20 mg orally.	5
Moderate Renal Impairment Participants with moderate renal impairment received a single dose of PF-07081532 20 mg orally.	5
Severe Renal Impairment Participants with severe renal impairment received a single dose of PF-07081532 20 mg orally.	8
Total	18

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Withdrawal by Subject	1	0	0

Baseline characteristics

Characteristic	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	Total
Age, Continuous	68.0 Years	63.0 Years	66.5 Years	66.0 Years
Body Mass Index (BMI)	29.1 kg/m^2 STANDARD_DEVIATION 8.12	31.2 kg/m^2 STANDARD_DEVIATION 6.89	33.7 kg/m^2 STANDARD_DEVIATION 7.86	31.7 kg/m^2 STANDARD_DEVIATION 7.49
Body Surface Area (BSA)-Unnormalized Estimated Glomerular Filtration Rate (eGFR)	80.6 Milliliters per minute (mL/min) STANDARD_DEVIATION 8.26	48.7 Milliliters per minute (mL/min) STANDARD_DEVIATION 6.43	15.7 Milliliters per minute (mL/min) STANDARD_DEVIATION 8.31	NA Milliliters per minute (mL/min)
Race/Ethnicity, Customized Black or African American	1 Participants	3 Participants	1 Participants	5 Participants
Race/Ethnicity, Customized White	4 Participants	2 Participants	7 Participants	13 Participants
Sex: Female, Male Female	3 Participants	2 Participants	2 Participants	7 Participants
Sex: Female, Male Male	2 Participants	3 Participants	6 Participants	11 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 5	0 / 8
other Total, other adverse events	1 / 5	2 / 5	1 / 8
serious Total, serious adverse events	0 / 5	0 / 5	0 / 8

Outcome results

Primary

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.