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

NCT05510245 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: C3991007
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Type 2 Diabetes; Renal Impairment

Keywords

Type 2 Diabetes; Renal impairment

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (4)

• 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)

• Number of Participants With Laboratory Test Abnormalities

  Pre-dose, 72 and 144 hours post dose on Day 1

• 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

• Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Categorical Criteria

  Pre-dose, and 144 hours post the dose on Day 1

Study Arms (4)

Group 1

EXPERIMENTAL

Participants without renal impairment will receive a single 20 mg dose of PF 07081532, administered orally

Drug: PF-07081532

Group 2

EXPERIMENTAL

Participants with mild renal impairment will receive a single 20 mg dose of PF 07081532, administered orally

Drug: PF-07081532

Group 3

EXPERIMENTAL

Participants with moderate renal impairment will receive a single 20 mg dose of PF 07081532, administered orally

Drug: PF-07081532

Group 4

EXPERIMENTAL

Participants with severe renal impairment will receive a single 20 mg dose of PF 07081532, administered orally

Drug: PF-07081532

Interventions

PF-07081532 DRUG

One PF-07081532 20 mg tablet, administered orally

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes, or history of diabetic ketoacidosis.
• 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
• Personal or family history of MTC or MEN2, or participants with suspected MTC per the investigator's judgement.
• History of acute pancreatitis within 6 months before Screening or any history of chronic pancreatitis.
• Urinary incontinence.
• Participants with acute renal disease.
• Renal allograft recipients.
• Participants who have previously received a kidney, liver, or heart transplant.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Genesis Clinical Research, LLC

Tampa, Florida, 33603, United States

Location

Prism Research LLC dba Nucleus Network

Saint Paul, Minnesota, 55114, United States

Location

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

The study was terminated due to the termination of clinical development of PF-07081532, and no participants without renal impairment were enrolled.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: August 22, 2022
• Study Start: August 29, 2022
• Primary Completion: July 20, 2023
• Study Completion: July 20, 2023
• Last Updated: November 5, 2024
• Results First Posted: November 5, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)