Diabetes Mellitus, Type 2Phase 1NCT04616027

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

A Phase 1 study testing PF-06882961 20 mg in people with Diabetes Mellitus, Type 2 and Renal Impairment, run by Pfizer at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Diabetes Mellitus, Type 2, Renal Impairment, Healthy
What is being tested?: PF-06882961 20 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 42 participants
Where: 3 sitesUnited States
Study dates: 13 Jan 2021to 18 Feb 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.
Additional Inclusion Criteria for Healthy Participants with Normal Renal

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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).
Additional Inclusion Criteria for T2DM Participants with Normal Renal
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.
Prohibited prior/concomitant medications.
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 2 is comparable to that in the pooled renal impairment groups (Cohorts 3, 4, and 5).
Additional Inclusion Criteria for T2DM Participants with Impaired Renal Function (Groups 3-5):
A prior diagnosis of T2DM with an HbA1c ≥6% and ≤10.5%, at Screening visit S1, confirmed by a single repeat, if deemed necessary.
Meet the eGFR criteria listed for Groups 3, 4, or 5 (for participants not on dialysis) in Table 1 based on an average of measures from Screening visits S1 and S2.
Stable concomitant medications, as defined in Section 6.5, for the management of medical conditions relevant to an individual participant's medical history. Participants receiving fluctuating concomitant medications/treatments may be considered, on a case-by-case basis with input from sponsor, if the underlying disease is stable.
For Group 5 participants on dialysis only, participants must have required hemodialysis for at least 6 weeks and need dialysis sessions 3 times per week

Who cannot join

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.

Show all 45Show fewer

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).
Known prior participation in a trial involving PF 06882961 or known hypersensitivity or intolerance to a GLP-1R agonist.
Screening standard 12-lead ECG that demonstrates a clinically relevant abnormality that requires further diagnostic evaluation or intervention (eg, new, clinically relevant arrhythmia, conduction disturbance, findings suggestive of ischemia). A potential participant whose pre-dose ECG (on Day 1, 0 hour) demonstrates a clinically relevant abnormality that requires further diagnostic evaluation or intervention will be considered a screen failure.
A positive COVID-19 test in the screening period.
A positive urine drug test (or other type of drug test in anuric participants on dialysis only).
Participants with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study specific central laboratory and confirmed by a single repeat test, if deemed necessary:
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥2 × upper limit of normal (ULN);
Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
Fasting C-peptide <0.8 ng/mL.
Fasting plasma glucose (FPG) >270 mg/dL (15 mmol/L) at screening (S1).
History of regular alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male participants (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
History of sensitivity to heparin or heparin-induced thrombocytopenia only if heparin is planned to flush intravenous catheters.
Additional Exclusion Criteria for Healthy Participants with Normal Renal
Function (Group 1):
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including clinically relevant and significant drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
Use of prescription or non-prescription drugs and dietary and herbal supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of IP). As an exception, ibuprofen or acetaminophen may be used at doses of ≤1 g/day. Limited use of non-prescription medications that are not believed to affect participant safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.
Screening seated systolic blood pressure (SBP) >140 mmHg or diastolic blood pressure (DBP) >90 mmHg, following at least 5 minutes of supine rest. If SBP is >140 mmHg or DBP >90 mmHg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
Participants with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study specific central laboratory and confirmed by a single repeat test, if deemed necessary:
HbA1c ≥6.0% at Screening visit S1; FPG ≥126 mg/dL at screening (S1); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.5 × upper limit of normal (ULN). Additional Exclusion Criteria for T2DM Participants with Normal Renal
Function (Group 2):
At Screening, seated systolic blood pressure (SBP) ≥160 mm Hg and/or diastolic blood pressure (DBP) ≥105 mm Hg after ≥5minute of seated rest, with a single repeat permitted to assess eligibility, if needed, at each of these 2 visits.
Additional Exclusion Criteria for T2DM Participants with Impaired Renal
Function (Groups 3-5) only:
At Screening, persistent severe, uncontrolled hypertension; for example: seated systolic blood pressure (SBP) ≥180 mm Hg and/or diastolic blood pressure (DBP) ≥105 mm Hg after ≥5minute of seated rest, with a single repeat permitted to assess eligibility, if needed, at each of these 2 visits: For subjects with SBP ≥160 mm Hg or DBP ≥100 mm Hg, the period between Screening and Day 1 must be used to refine the doses of the agents used for management of blood pressure with the aim to have stable BP on Day 1;.
For participants in Group 5 on Dialysis only: Hemodynamic instability during or at the conclusion of dialysis during the 2 weeks prior to dosing, as marked by symptomatic hypotension.
Criteria for Dosing on Day 1
Participants will progress to dosing on Day 1 provided they have satisfied all the following criteria:
In women of childbearing potential, urine pregnancy test on Day -1 is negative;
Cohort 1 and Cohort 2 only: Approval from the sponsor must be obtained before proceeding with dosing participants in either Cohort 1 or Cohort 2;
Cohorts 2-5 only: Participants must have measurement on Day 1 of SBP <160 mm Hg and DBP <100 mm Hg; A single repeat assessment is permitted, to confirm that the above criterion is met [and in such cases, the repeat assessment overrides initial results].

Trial locations and contacts

3 sites in 1 country.

United States3 sites

University of Miami Hospital
Miami, Florida, 33136
Orlando Clinical Research Center
Orlando, Florida, 32809
Prism Research LLC dba Nucleus Network
Saint Paul, Minnesota, 55114

Other trials in United States

About this study

Official title: A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL GROUP STUDY TO EVALUATE THE PHARMACOKINETICS OF PF-06882961 IN PARTICIPANTS WITH TYPE 2 DIABETES MELLITUS WITH VARYING DEGREES OF RENAL IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT RENAL IMPAIRMENT

Conditions: Diabetes Mellitus, Type 2, Renal Impairment, Healthy
Being tested: PF-06882961 20 mg
Medical subject headings: Diabetes Mellitus, Type 2, Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT04616027
Study group	Role	What they receive
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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: PF-06882961 20 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961
Cmax was the maximum observed plasma concentration and was directly observed from data.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Cmax,u was defined as maximum observed concentration of unbound drug.
Measured: 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
AUCinf,u was defined as unbound area under the plasma concentration-time profile from time zero extrapolated to infinite time.
Measured: 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
AUClast,u was defined as unbound area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration.
Measured: 0 (pre dose), 4 hours (post dose) on Day 1
Apparent Clearance (CL/F) of Plasma PF-06882961
Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period.
Measured: 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
CLu/F was defined as apparent clearance of unbound drug.
Measured: 0 (pre dose), 4 hours (post dose) on Day 1
Apparent Volume of Distribution (Vz/F) of Plasma PF-06882961
Vz/F was defined as apparent volume of distribution.
Measured: 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
Unbound Vz/F (Vz,u/F) of Plasma PF-06882961
Vz,u/F was defined as apparent volume of distribution of unbound drug.
Measured: 0 (pre dose), 4 hours (post dose) on Day 1
Time of Observed Maximum Plasma Concentration (Tmax) of Plasma PF-06882961
Tmax was defined as time to maximum observed concentration. Observed directly from data as time of first occurrence.
Measured: 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
Terminal Elimination Half-Life (T1/2) of Plasma PF-06882961
Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase.
Measured: 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
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason.
Measured: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Laboratory test abnormalities included hematology, chemistry and urinalysis.
Measured: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Number of Participants With Abnormal Vital Signs
The vital signs were measured included pulse rate (beats/min) and blood pressure (mmHg).
Measured: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Number of Participants With Abnormal Electrocardiograms (ECGs)
ECG parameters included QTCF, PR interval, and QRS interval.
Measured: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jan 202118 Feb 2022

First posted4 Nov 2020
Study start13 Jan 2021
Primary completion18 Feb 2022
Study completion18 Feb 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04616027
Sponsor's protocol ID: C3421012
Status last verified: Dec 2023
First submitted: 29 Oct 2020
Last updated: 10 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: 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.

Publications

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.
PubMed 37840155

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL GROUP STUDY TO EVALUATE THE PHARMACOKINETICS OF PF-06882961 IN PARTICIPANTS WITH TYPE 2 DIABETES MELLITUS WITH VARYING DEGREES OF RENAL IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT RENAL IMPAIRMENT
ClinicalTrials.gov ID: NCT04616027
Acronym / sponsor ID: C3421012
Conditions: Diabetes Mellitus, Type 2, Renal Impairment, Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 13 Jan 2021 (actual)
Primary completion: 18 Feb 2022 (actual)
Study completion: 18 Feb 2022 (actual)
First posted: 4 Nov 2020 (actual)
Results: Posted 10 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Healthy participants with normal renal function	Experimental	Drug: PF-06882961 20 mgThis arm includes participants with normal renal function who will receive an oral dose of PF-06882961 20 milligrams (mg) on Day 1
Participants with T2DM with normal renal function	Experimental	Drug: PF-06882961 20 mgThis 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
Participants with T2DM with mild renal impairment	Experimental	Drug: PF-06882961 20 mgThis 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
Participants with T2DM with moderate renal impairment	Experimental	Drug: PF-06882961 20 mgThis 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
Participants with T2DM with severe renal impairment	Experimental	Drug: PF-06882961 20 mgThis 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (27 listed)

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.

Key exclusion criteria (45 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PF-06882961 20 mgPF-06882961 20 mg single oral dose provided in tablet form administered in a fed state on Day 1	Drug	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

Primary outcome

Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961
Time frame: 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
Cmax was the maximum observed plasma concentration and was directly observed from data.
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-06882961
Time frame: 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
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-06882961
Time frame: 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
AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.
Fraction Unbound (fu) of Plasma PF-06882961
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Fu was defined as fraction of unbound drug in plasma.

13 secondary outcomes

Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961
Time frame: 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
Time frame: 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
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Apparent Clearance (CL/F) of Plasma PF-06882961
Time frame: 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
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Apparent Volume of Distribution (Vz/F) of Plasma PF-06882961
Time frame: 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
Unbound Vz/F (Vz,u/F) of Plasma PF-06882961
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Time of Observed Maximum Plasma Concentration (Tmax) of Plasma PF-06882961
Time frame: 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
Terminal Elimination Half-Life (T1/2) of Plasma PF-06882961
Time frame: 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
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities)
Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Number of Participants With Abnormal Vital Signs
Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Number of Participants With Abnormal Electrocardiograms (ECGs)
Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)

Results and safety

Results posted to the registry on 10 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Healthy and Normal Renal Function	8	8
T2DM Normal Renal Function	7	7
T2DM Mild Renal Impairment	8	8
T2DM Moderate Renal Impairment	8	8
T2DM Severe Renal Impairment	8	8

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961

Time frame: 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. Geometric mean (Geometric Coefficient of Variation). Unit: nanograms/milliliter (ng/mL)

Measure	Healthy and Normal Renal Function n = 8	T2DM Normal Renal Function n = 7	T2DM Mild Renal Impairment n = 7	T2DM Moderate Renal Impairment n = 8	T2DM Severe Renal Impairment n = 8
Value	38.80 (28)	38.67 (58)	39.19 (42)	56.68 (28)	39.18 (50)

Healthy and Normal Renal Function vs T2DM Normal Renal Function: Ratio (Test/Reference) of Adjusted Means: 99.67 (90% CI 70.15 to 141.60)
T2DM Normal Renal Function vs T2DM Mild Renal Impairment: Ratio (Test/Reference) of Adjusted Means: 101.34 (90% CI 70.51 to 145.63)
T2DM Normal Renal Function vs T2DM Moderate Renal Impairment: Ratio (Test/Reference) of Adjusted Means: 146.56 (90% CI 103.16 to 208.22)

Population analysed: All participants who received at least 1 dose of PF-06882961 and had at least 1 of the plasma PK parameters of interest calculated. Here, overall number of participants analyzed signifies number of participants evaluable for this outcome measure.

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

Measure	Healthy and Normal Renal Function n = 8	T2DM Normal Renal Function n = 7	T2DM Mild Renal Impairment n = 6	T2DM Moderate Renal Impairment n = 7	T2DM Severe Renal Impairment n = 8
Value	362.4 (30)	404.8 (49)	487.0 (19)	543.2 (48)	408.8 (46)

Healthy and Normal Renal Function vs T2DM Normal Renal Function: Ratio (Test/Reference) of Adjusted Means: 111.71 (90% CI 79.52 to 156.93)
T2DM Normal Renal Function vs T2DM Mild Renal Impairment: Ratio (Test/Reference) of Adjusted Means: 120.31 (90% CI 83.49 to 173.38)
T2DM Normal Renal Function vs T2DM Moderate Renal Impairment: Ratio (Test/Reference) of Adjusted Means: 134.18 (90% CI 94.46 to 190.62)

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

Measure	Healthy and Normal Renal Function n = 8	T2DM Normal Renal Function n = 7	T2DM Mild Renal Impairment n = 7	T2DM Moderate Renal Impairment n = 8	T2DM Severe Renal Impairment n = 8
Value	359.9 (30)	399.6 (50)	466.3 (19)	538.2 (44)	404.8 (46)

Healthy and Normal Renal Function vs T2DM Normal Renal Function: Ratio (Test/Reference) of Adjusted Means: 111.02 (90% CI 79.60 to 154.86)
T2DM Normal Renal Function vs T2DM Mild Renal Impairment: Ratio (Test/Reference) of Adjusted Means: 116.70 (90% CI 82.76 to 164.56)
T2DM Normal Renal Function vs T2DM Moderate Renal Impairment: Ratio (Test/Reference) of Adjusted Means: 134.68 (90% CI 96.56 to 187.85)

Primary outcome: Fraction Unbound (fu) of Plasma PF-06882961

Time frame: 0 (pre dose), 4 hours (post dose) on Day 1. Geometric mean (Geometric Coefficient of Variation). Unit: Ratio

Measure	Healthy and Normal Renal Function n = 8	T2DM Normal Renal Function n = 7	T2DM Mild Renal Impairment n = 7	T2DM Moderate Renal Impairment n = 8	T2DM Severe Renal Impairment n = 8
Value	0.01519 (9)	0.01542 (15)	0.01699 (14)	0.01861 (18)	0.01960 (18)

Healthy and Normal Renal Function vs T2DM Normal Renal Function: Ratio (Test/Reference) of Adjusted Means: 101.52 (90% CI 88.89 to 115.94)
T2DM Normal Renal Function vs T2DM Mild Renal Impairment: Ratio (Test/Reference) of Adjusted Means: 110.17 (90% CI 96.05 to 126.37)
T2DM Normal Renal Function vs T2DM Moderate Renal Impairment: Ratio (Test/Reference) of Adjusted Means: 120.63 (90% CI 105.63 to 137.77)

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Healthy and Normal Renal Function	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
T2DM Normal Renal Function	0 of 7 (0%)	6 of 7 (85.7%)	0 of 7
T2DM Mild Renal Impairment	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
T2DM Moderate Renal Impairment	0 of 8 (0%)	2 of 8 (25%)	0 of 8
T2DM Severe Renal Impairment	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Total	0 of 39 (0%)	12 of 39 (30.8%)	0 of 39

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37840155Fediuk 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.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-06882961 20 mg in people with Diabetes Mellitus, Type 2 and Renal Impairment, run by Pfizer at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961 (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04616027, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2024.