STUDY OF PF-06882961 IN PARTICIPANTS WITH TYPE 2 DIABETES MELLITUS WITH VARYING DEGREES OF RENAL IMPAIRMENT AND PARTICIPANTS WITHOUT RENAL IMPAIRMENT

NCT04616027 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C3421012
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

This study will characterize the effect of varying degrees of renal impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of PF- 06882961 compared with participants with normal renal function.

Conditions

Diabetes Mellitus, Type 2; Renal Impairment; Healthy

Outcome Measures

Primary Outcomes (4)

• Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961

  Cmax was the maximum observed plasma concentration and was directly observed from data.

  0 (pre dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours (post dose) on Day 1, 24 and 36 hours (post dose) on Day 2, 48 hours (post dose) on Day 3

• Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-06882961

  AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.

  0 (pre dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours (post dose) on Day 1, 24 and 36 hours (post dose) on Day 2, 48 hours (post dose) on Day 3

• Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-06882961

  AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.

  0 (pre dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours (post dose) on Day 1, 24 and 36 hours (post dose) on Day 2, 48 hours (post dose) on Day 3

• Fraction Unbound (fu) of Plasma PF-06882961

  Fu was defined as fraction of unbound drug in plasma.

  0 (pre dose), 4 hours (post dose) on Day 1

Secondary Outcomes (13)

• Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961

  0 (pre dose), 4 hours (post dose) on Day 1

• Unbound Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf,u) of Plasma PF-06882961

  0 (pre dose), 4 hours (post dose) on Day 1

• Unbound Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast,u) of Plasma PF-06882961

  0 (pre dose), 4 hours (post dose) on Day 1

• Apparent Clearance (CL/F) of Plasma PF-06882961

  0 (pre dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 hours (post dose) on Day 1, 24 and 36 hours (post dose) on Day 2, 48 hours (post dose) on Day 3

• Apparent Clearance of Unbound Drug After Oral Administration (CLu/F) of Plasma PF-06882961

  0 (pre dose), 4 hours (post dose) on Day 1

Study Arms (5)

Healthy participants with normal renal function

EXPERIMENTAL

This arm includes participants with normal renal function who will receive an oral dose of PF-06882961 20 milligrams (mg) on Day 1

Drug: PF-06882961 20 mg

Participants with T2DM with normal renal function

EXPERIMENTAL

This arm includes participants with Type 2 Diabetes Mellitus (T2DM) with normal renal function who will receive an oral dose of PF-06882961 20 mg on Day 1

Drug: PF-06882961 20 mg

Participants with T2DM with mild renal impairment

EXPERIMENTAL

This arm includes participants with Type 2 Diabetes Mellitus (T2DM) with mild renal impairment who will receive an oral dose of PF-06882961 20 mg on Day 1

Drug: PF-06882961 20 mg

Participants with T2DM with moderate renal impairment

EXPERIMENTAL

This arm includes participants with Type 2 Diabetes Mellitus (T2DM) with moderate renal impairment who will receive an oral dose of PF-06882961 20 mg on Day 1

Drug: PF-06882961 20 mg

Participants with T2DM with severe renal impairment

EXPERIMENTAL

This arm includes participants with Type 2 Diabetes Mellitus (T2DM) with severe renal impairment who will receive an oral dose of PF-06882961 20 mg on Day 1

Drug: PF-06882961 20 mg

Interventions

PF-06882961 20 mg DRUG

PF-06882961 20 mg single oral dose provided in tablet form administered in a fed state on Day 1

Healthy participants with normal renal function; Participants with T2DM with mild renal impairment; Participants with T2DM with moderate renal impairment; Participants with T2DM with normal renal function; Participants with T2DM with severe renal impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• 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 eGFR (as calculated by the sponsor-identified central laboratory using the CKD-EPI equation)1 obtained at Screening visits S1 and S2. The average of the 2 eGFR values obtained from S1 and S2 will be used for study enrollment and assignment to appropriate renal function group. Note: participants on dialysis will be placed in Group 5 regardless of eGFR from S1 and S2 (S2 is optional for dialysis participants only).
• Male and female participants must be ≥18 years of age, inclusive, at the time of signing the informed consent document (ICD).
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures, including the ability to perform self-monitoring blood glucose at a frequency deemed appropriate by the investigator.
• Body mass index (BMI) of ≥18.0 kg/m2 and \<45.4 kg/m2; and a total body weight \>50 kg (110 lb).
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
• Function (Group 1):
• No clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate measurement, standard 12-lead ECG and clinical laboratory tests.
• Normal renal function (mean eGFR ≥90 mL/min) based on an average of measures from Screening visits S1 and S2.
• Demographically comparable to participants with impaired renal function:
• A body weight within ±15 kg of the mean body weight of the pooled renal impairment groups (Groups 3, 4, and 5), as provided by sponsor;
• An age within ±10 years of the mean age of the pooled renal impairment groups (Groups 3, 4 and 5), as provided by sponsor;
• 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 (Cohorts 3, 4, and 5).
• Function (Group 2):
• A prior diagnosis of T2DM with an HbA1c ≥6% and ≤10.5%, at Screening visit S1, confirmed by a single repeat, if deemed necessary.
• Normal renal function (mean eGFR ≥90 mL/min) based on an average of measures from Screening visits S1 and S2.

You may not qualify if:

• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency). NOTE: subjects who have undergone cholecystectomy and/or appendectomy are eligible for this study so long as the surgery occurred more than 6 months prior to Screening;
• Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin); a participant is considered cured if there has been no evidence of cancer recurrence in the previous 5 years.
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), or participants with suspected MTC per the investigator's judgement.
• History of chronic or acute pancreatitis within 5 years.
• Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes.
• 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 visit S1.
• Urinary incontinence.
• Participants with acute renal disease.
• Renal allograft recipients.
• Participants with other clinically significant disease, in the judgment of the investigator that may affect the safety of the participant or that may affect the PK of PF 06882961.
• Prohibited prior/concomitant medications.
• Compliance with details regarding prohibited prior/concomitant medications.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of IP used in this study (whichever is longer).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Prism Research LLC dba Nucleus Network

Saint Paul, Minnesota, 55114, United States

Location

Related Publications (1)

• Fediuk DJ, Gorman DN, Stoddard SA, Zhang Y, Ogden AG, Winton JA, Saxena AR. Effect of Renal Impairment on the Pharmacokinetics of a Single Oral Dose of Danuglipron in Participants With Type 2 Diabetes. J Clin Pharmacol. 2024 Apr;64(4):449-460. doi: 10.1002/jcph.2371. Epub 2023 Nov 2.

  PMID: 37840155 DERIVED

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency

Interventions

danuglipron

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

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: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2020
• First Posted: November 4, 2020
• Study Start: January 13, 2021
• Primary Completion: February 18, 2022
• Study Completion: February 18, 2022
• Last Updated: May 10, 2024
• Results First Posted: May 10, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)