Diabetes Mellitus, Type 2, Healthy, Renal Impairment
Conditions
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.
Interventions
DRUGPF-06882961 20 mg
PF-06882961 20 mg single oral dose provided in tablet form administered in a fed state on Day 1
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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 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: 1. 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; 2. An age within ±10 years of the mean age of the pooled renal impairment groups (Groups 3, 4 and 5), as provided by sponsor; 3. 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: 1. 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; 2. An age within ±10 years of the mean age of the pooled renal impairment groups (Groups 3, 4, and 5), as provided by sponsor; 3. 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
Exclusion criteria
* 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). * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) 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 | 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 | 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 | 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 | 0 (pre dose), 4 hours (post dose) on Day 1 | Fu was defined as fraction of unbound drug in plasma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Clearance of Unbound Drug After Oral Administration (CLu/F) of Plasma PF-06882961 | 0 (pre dose), 4 hours (post dose) on Day 1 | CLu/F was defined as apparent clearance of unbound drug. |
| Apparent Volume of Distribution (Vz/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 | Vz/F was defined as apparent volume of distribution. |
| Unbound Vz/F (Vz,u/F) of Plasma PF-06882961 | 0 (pre dose), 4 hours (post dose) on Day 1 | Vz,u/F was defined as apparent volume of distribution of unbound drug. |
| Time of Observed Maximum Plasma Concentration (Tmax) 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 | Tmax was defined as time to maximum observed concentration. Observed directly from data as time of first occurrence. |
| Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961 | 0 (pre dose), 4 hours (post dose) on Day 1 | Cmax,u was defined as maximum observed concentration of unbound drug. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months) | 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. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months) | Laboratory test abnormalities included hematology, chemistry and urinalysis. |
| Number of Participants With Abnormal Vital Signs | From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months) | The vital signs were measured included pulse rate (beats/min) and blood pressure (mmHg). |
| Number of Participants With Abnormal Electrocardiograms (ECGs) | From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months) | ECG parameters included QTCF, PR interval, and QRS interval. |
| Terminal Elimination Half-Life (T1/2) 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 | Plasma terminal elimination half-life (T1/2) is the time measured for the plasma concentration to decrease by one half at the terminal phase. |
| 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 | AUCinf,u was defined as unbound area under the plasma concentration-time profile from time zero extrapolated to infinite time. |
| 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 | AUClast,u was defined as unbound area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration. |
| 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 After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. |
Countries
United States
Participant flow
Pre-assignment details
Participants were allocated to treatment at 3 sites in 1 country. 42 participants were allocated to treatment, 3 did not receive treatment. A total of 39 participants were treated and completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Healthy and Normal Renal Function Healthy participants whose estimated glomerular filtration rate (eGFR) ≥90mL/min were included in this group. PF-06882961 was administered at a dose of 20 mg on Day 1. | 8 |
| T2DM Normal Renal Function Participants with type 2 diabetes mellitus (T2DM) whose estimated glomerular filtration rate (eGFR) ≥90mL/min were included in this group. PF-06882961 was administered at a dose of 20 mg on Day 1. | 7 |
| T2DM Mild Renal Impairment Participants with T2DM whose estimated glomerular filtration rate (eGFR) 60-89mL/min were included in this group. PF-06882961 was administered at a dose of 20 mg on Day 1. | 8 |
| T2DM Moderate Renal Impairment Participants with T2DM whose estimated glomerular filtration rate (eGFR) 30-59mL/min were included in this group. PF-06882961 was administered at a dose of 20 mg on Day 1. | 8 |
| T2DM Severe Renal Impairment Participants with T2DM whose estimated glomerular filtration rate (eGFR) \<30mL/min were included in this group. PF-06882961 was administered at a dose of 20 mg on Day 1. | 8 |
| Total | 39 |
Baseline characteristics
| Characteristic | Total | T2DM Severe Renal Impairment | T2DM Moderate Renal Impairment | T2DM Mild Renal Impairment | T2DM Normal Renal Function | Healthy and Normal Renal Function |
|---|---|---|---|---|---|---|
| Age, Continuous | 63.2 Years STANDARD_DEVIATION 8.31 | 59.8 Years STANDARD_DEVIATION 4.98 | 67.0 Years STANDARD_DEVIATION 9.09 | 68.0 Years STANDARD_DEVIATION 10.9 | 64.1 Years STANDARD_DEVIATION 7.17 | 57.1 Years STANDARD_DEVIATION 2.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 4 Participants | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 4 Participants | 5 Participants | 6 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 4 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 4 Participants | 7 Participants | 7 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Female | 18 Participants | 2 Participants | 4 Participants | 5 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 21 Participants | 6 Participants | 4 Participants | 3 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 39 |
| other Total, other adverse events | 1 / 8 | 6 / 7 | 1 / 8 | 2 / 8 | 2 / 8 | 12 / 39 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 39 |
Outcome results
Primary
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-06882961 | 362.4 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| T2DM Normal Renal Function | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-06882961 | 404.8 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 49 |
| T2DM Mild Renal Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-06882961 | 487.0 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
| T2DM Moderate Renal Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-06882961 | 543.2 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 48 |
| T2DM Severe Renal Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-06882961 | 408.8 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 46 |
Comparison: T2DM Normal Renal Function was test, Healthy and Normal Renal Function was reference.90% CI: [79.52, 156.93]
Comparison: T2DM Mild Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [83.49, 173.38]
Comparison: T2DM Moderate Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [94.46, 190.62]
Comparison: T2DM Severe Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [71.89, 141.87]
Primary
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-06882961 | 359.9 ng*hr/mL | Geometric Coefficient of Variation 30 |
| T2DM Normal Renal Function | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-06882961 | 399.6 ng*hr/mL | Geometric Coefficient of Variation 50 |
| T2DM Mild Renal Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-06882961 | 466.3 ng*hr/mL | Geometric Coefficient of Variation 19 |
| T2DM Moderate Renal Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-06882961 | 538.2 ng*hr/mL | Geometric Coefficient of Variation 44 |
| T2DM Severe Renal Impairment | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-06882961 | 404.8 ng*hr/mL | Geometric Coefficient of Variation 46 |
Comparison: T2DM Normal Renal Function was test, Healthy and Normal Renal Function was reference.90% CI: [79.6, 154.86]
Comparison: T2DM Mild Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [82.76, 164.56]
Comparison: T2DM Moderate Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [96.56, 187.85]
Comparison: T2DM Severe Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [72.63, 141.3]
Primary
Fraction Unbound (fu) of Plasma PF-06882961
Fu was defined as fraction of unbound drug in plasma.
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Fraction Unbound (fu) of Plasma PF-06882961 | 0.01519 Ratio | Geometric Coefficient of Variation 9 |
| T2DM Normal Renal Function | Fraction Unbound (fu) of Plasma PF-06882961 | 0.01542 Ratio | Geometric Coefficient of Variation 15 |
| T2DM Mild Renal Impairment | Fraction Unbound (fu) of Plasma PF-06882961 | 0.01699 Ratio | Geometric Coefficient of Variation 14 |
| T2DM Moderate Renal Impairment | Fraction Unbound (fu) of Plasma PF-06882961 | 0.01861 Ratio | Geometric Coefficient of Variation 18 |
| T2DM Severe Renal Impairment | Fraction Unbound (fu) of Plasma PF-06882961 | 0.01960 Ratio | Geometric Coefficient of Variation 18 |
Comparison: T2DM Normal Renal Function was test, Healthy and Normal Renal Function was reference.90% CI: [88.89, 115.94]
Comparison: T2DM Mild Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [96.05, 126.37]
Comparison: T2DM Moderate Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [105.63, 137.77]
Comparison: T2DM Severe Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [111.26, 145.12]
Primary
Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961
Cmax was the maximum observed plasma concentration and was directly observed from data.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961 | 38.80 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| T2DM Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961 | 38.67 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| T2DM Mild Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961 | 39.19 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 42 |
| T2DM Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961 | 56.68 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| T2DM Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Plasma PF-06882961 | 39.18 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
Comparison: T2DM Normal Renal Function was test, Healthy and Normal Renal Function was reference.90% CI: [70.15, 141.6]
Comparison: T2DM Mild Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [70.51, 145.63]
Comparison: T2DM Moderate Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [103.16, 208.22]
Comparison: T2DM Severe Renal Impairment was test, T2DM Normal Renal Function was reference.90% CI: [71.31, 143.92]
Secondary
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.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Apparent Clearance (CL/F) of Plasma PF-06882961 | 55.17 liter per hour (L/hr) | Geometric Coefficient of Variation 30 |
| T2DM Normal Renal Function | Apparent Clearance (CL/F) of Plasma PF-06882961 | 49.32 liter per hour (L/hr) | Geometric Coefficient of Variation 49 |
| T2DM Mild Renal Impairment | Apparent Clearance (CL/F) of Plasma PF-06882961 | 41.08 liter per hour (L/hr) | Geometric Coefficient of Variation 19 |
| T2DM Moderate Renal Impairment | Apparent Clearance (CL/F) of Plasma PF-06882961 | 36.83 liter per hour (L/hr) | Geometric Coefficient of Variation 48 |
| T2DM Severe Renal Impairment | Apparent Clearance (CL/F) of Plasma PF-06882961 | 48.93 liter per hour (L/hr) | Geometric Coefficient of Variation 46 |
Secondary
Apparent Clearance of Unbound Drug After Oral Administration (CLu/F) of Plasma PF-06882961
CLu/F was defined as apparent clearance of unbound drug.
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Apparent Clearance of Unbound Drug After Oral Administration (CLu/F) of Plasma PF-06882961 | 3631 L/hr | Geometric Coefficient of Variation 37 |
| T2DM Normal Renal Function | Apparent Clearance of Unbound Drug After Oral Administration (CLu/F) of Plasma PF-06882961 | 3200 L/hr | Geometric Coefficient of Variation 45 |
| T2DM Mild Renal Impairment | Apparent Clearance of Unbound Drug After Oral Administration (CLu/F) of Plasma PF-06882961 | 2525 L/hr | Geometric Coefficient of Variation 16 |
| T2DM Moderate Renal Impairment | Apparent Clearance of Unbound Drug After Oral Administration (CLu/F) of Plasma PF-06882961 | 2000 L/hr | Geometric Coefficient of Variation 31 |
| T2DM Severe Renal Impairment | Apparent Clearance of Unbound Drug After Oral Administration (CLu/F) of Plasma PF-06882961 | 2494 L/hr | Geometric Coefficient of Variation 50 |
Secondary
Apparent Volume of Distribution (Vz/F) of Plasma PF-06882961
Vz/F was defined as apparent volume of distribution.
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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Apparent Volume of Distribution (Vz/F) of Plasma PF-06882961 | 600.8 liter (L) | Geometric Coefficient of Variation 59 |
| T2DM Normal Renal Function | Apparent Volume of Distribution (Vz/F) of Plasma PF-06882961 | 552.3 liter (L) | Geometric Coefficient of Variation 89 |
| T2DM Mild Renal Impairment | Apparent Volume of Distribution (Vz/F) of Plasma PF-06882961 | 372.5 liter (L) | Geometric Coefficient of Variation 38 |
| T2DM Moderate Renal Impairment | Apparent Volume of Distribution (Vz/F) of Plasma PF-06882961 | 438.4 liter (L) | Geometric Coefficient of Variation 85 |
| T2DM Severe Renal Impairment | Apparent Volume of Distribution (Vz/F) of Plasma PF-06882961 | 565.9 liter (L) | Geometric Coefficient of Variation 48 |
Secondary
Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961
Cmax,u was defined as maximum observed concentration of unbound drug.
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961 | 0.5896 ng/mL | Geometric Coefficient of Variation 34 |
| T2DM Normal Renal Function | Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961 | 0.5963 ng/mL | Geometric Coefficient of Variation 60 |
| T2DM Mild Renal Impairment | Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961 | 0.6662 ng/mL | Geometric Coefficient of Variation 32 |
| T2DM Moderate Renal Impairment | Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961 | 1.055 ng/mL | Geometric Coefficient of Variation 25 |
| T2DM Severe Renal Impairment | Maximum Observed Concentration of Unbound Drug (Cmax,u) of Plasma PF-06882961 | 0.7680 ng/mL | Geometric Coefficient of Variation 57 |
Secondary
Number of Participants With Abnormal Electrocardiograms (ECGs)
ECG parameters included QTCF, PR interval, and QRS interval.
Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Chg > 60 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 25/50% | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 30 < Chg ≤ 60 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 50% | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 300 | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 1 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 50% | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140 | 1 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Chg > 60 | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 25/50% | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 300 | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 30 < Chg ≤ 60 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 300 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 25/50% | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 50% | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 30 < Chg ≤ 60 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Chg > 60 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 50% | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 25/50% | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Chg > 60 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 30 < Chg ≤ 60 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 300 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 1 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 300 | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 50% | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140 | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 | 2 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Chg > 60 | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): 30 < Chg ≤ 60 | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | QTCF NOT OTHERWISE SPECIFIED (MSEC): Value > 500 | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Electrocardiograms (ECGs) | PR INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Chg ≥ 25/50% | 0 Participants |
Secondary
Number of Participants With Abnormal Vital Signs
The vital signs were measured included pulse rate (beats/min) and blood pressure (mmHg).
Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy and Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Value < 90mmHg | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg increase | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg decrease | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Value < 50 mmHg | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg increase | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg decrease | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value < 40 bpm | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value > 120 bpm | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg decrease | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg decrease | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Value < 90mmHg | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Value < 50 mmHg | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg increase | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value > 120 bpm | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg increase | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value < 40 bpm | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value < 40 bpm | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value > 120 bpm | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Value < 50 mmHg | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg decrease | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg decrease | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg increase | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Value < 90mmHg | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg increase | 1 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg increase | 1 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg decrease | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Value < 50 mmHg | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg increase | 1 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg decrease | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value > 120 bpm | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Value < 90mmHg | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value < 40 bpm | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Value < 50 mmHg | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value > 120 bpm | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg decrease | 1 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Vital Signs | PULSE RATE (BPM): Value < 40 bpm | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Value < 90mmHg | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg decrease | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING SYSTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 30mmHg increase | 1 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Abnormal Vital Signs | SITTING DIASTOLIC BLOOD PRESSURE (MMHG): Chg ≥ 20mmHg increase | 1 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Laboratory test abnormalities included hematology, chemistry and urinalysis.
Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Magnesium (mg/dL) < 0.9x LLN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Urate (mg/dL) > 1.2x ULN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Creatinine (mg/dL) > 1.3x ULN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bilirubin (mg/dL) > 1.5x ULN | 1 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Blood Urea Nitrogen (mg/dL) > 1.3x ULN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Leukocyte Esterase ≥ 1 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Ery. Mean Corpuscular HGB Concentration (g/dL) < 0.9x LLN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Erythrocytes (10^6/mm^3) < 0.8x LLN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Protein (Scalar) ≥ 1 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Glucose (Scalar) ≥ 1 | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Triacylglycerol Lipase (U/L) > 1.5x ULN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Lymphocytes (10^3/mm^3) < 0.8x LLN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Bacteria (/HPF) > 20 | 1 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Glucose (mg/dL) > 1.5x ULN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bicarbonate (mEq/L) < 0.9x LLN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Phosphate (mg/dL) > 1.2x ULN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Eosinophils (10^3/mm^3) > 1.2x ULN | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Hyaline Casts (/LPF) > 1 | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bilirubin (mg/dL) > 1.5x ULN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Erythrocytes (10^6/mm^3) < 0.8x LLN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Ery. Mean Corpuscular HGB Concentration (g/dL) < 0.9x LLN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Lymphocytes (10^3/mm^3) < 0.8x LLN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Eosinophils (10^3/mm^3) > 1.2x ULN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Blood Urea Nitrogen (mg/dL) > 1.3x ULN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Creatinine (mg/dL) > 1.3x ULN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Urate (mg/dL) > 1.2x ULN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Magnesium (mg/dL) < 0.9x LLN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Phosphate (mg/dL) > 1.2x ULN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bicarbonate (mEq/L) < 0.9x LLN | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Glucose (mg/dL) > 1.5x ULN | 4 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Triacylglycerol Lipase (U/L) > 1.5x ULN | 2 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Glucose (Scalar) ≥ 1 | 1 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Protein (Scalar) ≥ 1 | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Leukocyte Esterase ≥ 1 | 1 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Hyaline Casts (/LPF) > 1 | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Bacteria (/HPF) > 20 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Bacteria (/HPF) > 20 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Lymphocytes (10^3/mm^3) < 0.8x LLN | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Blood Urea Nitrogen (mg/dL) > 1.3x ULN | 4 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Glucose (mg/dL) > 1.5x ULN | 3 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Leukocyte Esterase ≥ 1 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Protein (Scalar) ≥ 1 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Ery. Mean Corpuscular HGB Concentration (g/dL) < 0.9x LLN | 2 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Glucose (Scalar) ≥ 1 | 2 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Triacylglycerol Lipase (U/L) > 1.5x ULN | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Eosinophils (10^3/mm^3) > 1.2x ULN | 1 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Erythrocytes (10^6/mm^3) < 0.8x LLN | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Phosphate (mg/dL) > 1.2x ULN | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Urate (mg/dL) > 1.2x ULN | 1 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bilirubin (mg/dL) > 1.5x ULN | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Magnesium (mg/dL) < 0.9x LLN | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Hyaline Casts (/LPF) > 1 | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bicarbonate (mEq/L) < 0.9x LLN | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Creatinine (mg/dL) > 1.3x ULN | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Eosinophils (10^3/mm^3) > 1.2x ULN | 1 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Urate (mg/dL) > 1.2x ULN | 1 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Erythrocytes (10^6/mm^3) < 0.8x LLN | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Magnesium (mg/dL) < 0.9x LLN | 1 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Bacteria (/HPF) > 20 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Phosphate (mg/dL) > 1.2x ULN | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Lymphocytes (10^3/mm^3) < 0.8x LLN | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bicarbonate (mEq/L) < 0.9x LLN | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Hyaline Casts (/LPF) > 1 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Glucose (mg/dL) > 1.5x ULN | 5 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Triacylglycerol Lipase (U/L) > 1.5x ULN | 1 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Ery. Mean Corpuscular HGB Concentration (g/dL) < 0.9x LLN | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Glucose (Scalar) ≥ 1 | 2 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Protein (Scalar) ≥ 1 | 4 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bilirubin (mg/dL) > 1.5x ULN | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Blood Urea Nitrogen (mg/dL) > 1.3x ULN | 5 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Leukocyte Esterase ≥ 1 | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Creatinine (mg/dL) > 1.3x ULN | 3 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Glucose (mg/dL) > 1.5x ULN | 3 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Creatinine (mg/dL) > 1.3x ULN | 8 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Protein (Scalar) ≥ 1 | 4 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Erythrocytes (10^6/mm^3) < 0.8x LLN | 1 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bicarbonate (mEq/L) < 0.9x LLN | 1 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Phosphate (mg/dL) > 1.2x ULN | 2 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Urate (mg/dL) > 1.2x ULN | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Bilirubin (mg/dL) > 1.5x ULN | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Lymphocytes (10^3/mm^3) < 0.8x LLN | 1 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Magnesium (mg/dL) < 0.9x LLN | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Leukocyte Esterase ≥ 1 | 1 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Blood Urea Nitrogen (mg/dL) > 1.3x ULN | 8 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Clinical Chemistry: Triacylglycerol Lipase (U/L) > 1.5x ULN | 2 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Hyaline Casts (/LPF) > 1 | 1 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Eosinophils (10^3/mm^3) > 1.2x ULN | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: URINE Glucose (Scalar) ≥ 1 | 2 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Hematology: Ery. Mean Corpuscular HGB Concentration (g/dL) < 0.9x LLN | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Urinalysis: Bacteria (/HPF) > 20 | 0 Participants |
Secondary
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.
Time frame: From the first dose of study intervention to the last dose of study treatment date +35 days (up to 13 months)
Population: All participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy and Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with serious adverse events | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with severe adverse events | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with adverse events | 1 Participants |
| Healthy and Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Healthy and Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued from study due to adverse events | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with serious adverse events | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with severe adverse events | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with adverse events | 6 Participants |
| T2DM Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| T2DM Normal Renal Function | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued from study due to adverse events | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued from study due to adverse events | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with adverse events | 1 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with serious adverse events | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| T2DM Mild Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with severe adverse events | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued from study due to adverse events | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with severe adverse events | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with adverse events | 2 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| T2DM Moderate Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with serious adverse events | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with serious adverse events | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with adverse events | 2 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants with severe adverse events | 0 Participants |
| T2DM Severe Renal Impairment | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causalities) | Participants discontinued from study due to adverse events | 0 Participants |
Secondary
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.
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Terminal Elimination Half-Life (T1/2) of Plasma PF-06882961 | 8.111 hr | Standard Deviation 3.4828 |
| T2DM Normal Renal Function | Terminal Elimination Half-Life (T1/2) of Plasma PF-06882961 | 8.139 hr | Standard Deviation 2.564 |
| T2DM Mild Renal Impairment | Terminal Elimination Half-Life (T1/2) of Plasma PF-06882961 | 6.640 hr | Standard Deviation 2.6551 |
| T2DM Moderate Renal Impairment | Terminal Elimination Half-Life (T1/2) of Plasma PF-06882961 | 8.907 hr | Standard Deviation 4.0497 |
| T2DM Severe Renal Impairment | Terminal Elimination Half-Life (T1/2) of Plasma PF-06882961 | 8.058 hr | Standard Deviation 0.84962 |
Secondary
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.
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy and Normal Renal Function | Time of Observed Maximum Plasma Concentration (Tmax) of Plasma PF-06882961 | 5.00 hour (hr) |
| T2DM Normal Renal Function | Time of Observed Maximum Plasma Concentration (Tmax) of Plasma PF-06882961 | 5.00 hour (hr) |
| T2DM Mild Renal Impairment | Time of Observed Maximum Plasma Concentration (Tmax) of Plasma PF-06882961 | 6.00 hour (hr) |
| T2DM Moderate Renal Impairment | Time of Observed Maximum Plasma Concentration (Tmax) of Plasma PF-06882961 | 5.50 hour (hr) |
| T2DM Severe Renal Impairment | Time of Observed Maximum Plasma Concentration (Tmax) of Plasma PF-06882961 | 5.00 hour (hr) |
Secondary
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.
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Unbound Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf,u) of Plasma PF-06882961 | 5.505 ng*hr/mL | Geometric Coefficient of Variation 37 |
| T2DM Normal Renal Function | Unbound Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf,u) of Plasma PF-06882961 | 6.246 ng*hr/mL | Geometric Coefficient of Variation 45 |
| T2DM Mild Renal Impairment | Unbound Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf,u) of Plasma PF-06882961 | 7.931 ng*hr/mL | Geometric Coefficient of Variation 16 |
| T2DM Moderate Renal Impairment | Unbound Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf,u) of Plasma PF-06882961 | 10.01 ng*hr/mL | Geometric Coefficient of Variation 31 |
| T2DM Severe Renal Impairment | Unbound Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf,u) of Plasma PF-06882961 | 8.019 ng*hr/mL | Geometric Coefficient of Variation 50 |
Secondary
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.
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | 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 | 5.470 ng*hr/mL | Geometric Coefficient of Variation 38 |
| T2DM Normal Renal Function | 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 | 6.162 ng*hr/mL | Geometric Coefficient of Variation 46 |
| T2DM Mild Renal Impairment | 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 | 7.922 ng*hr/mL | Geometric Coefficient of Variation 14 |
| T2DM Moderate Renal Impairment | 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 | 10.01 ng*hr/mL | Geometric Coefficient of Variation 30 |
| T2DM Severe Renal Impairment | 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 | 7.927 ng*hr/mL | Geometric Coefficient of Variation 50 |
Secondary
Unbound Vz/F (Vz,u/F) of Plasma PF-06882961
Vz,u/F was defined as apparent volume of distribution of unbound drug.
Time frame: 0 (pre dose), 4 hours (post dose) on Day 1
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy and Normal Renal Function | Unbound Vz/F (Vz,u/F) of Plasma PF-06882961 | 39530 Liter | Geometric Coefficient of Variation 68 |
| T2DM Normal Renal Function | Unbound Vz/F (Vz,u/F) of Plasma PF-06882961 | 35810 Liter | Geometric Coefficient of Variation 84 |
| T2DM Mild Renal Impairment | Unbound Vz/F (Vz,u/F) of Plasma PF-06882961 | 22890 Liter | Geometric Coefficient of Variation 30 |
| T2DM Moderate Renal Impairment | Unbound Vz/F (Vz,u/F) of Plasma PF-06882961 | 23800 Liter | Geometric Coefficient of Variation 63 |
| T2DM Severe Renal Impairment | Unbound Vz/F (Vz,u/F) of Plasma PF-06882961 | 28900 Liter | Geometric Coefficient of Variation 51 |