Renal Impairment, Type 2 Diabetes Mellitus
Conditions
Brief summary
This is a study to evaluate the effect of renal impairment on the pharmacokinetics, pharmacodynamics, safety and tolerability of ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and in healthy participants with normal renal function.
Interventions
DRUGErtugliflozin
Single oral administration of 3 X 5 mg tablets.
Sponsors
Pfizer
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Body Mass Index (BMI) of approximately 18 to 40 kg/m\^2 * Stable renal function * Male or female not of reproductive potential * Female of reproductive potential must agree or have their partner agree to use 2 acceptable methods of contraception * Healthy subjects determined to be healthy by investigator screening * T2DM participants have a diagnosis of T2DM as per American Diabetes Association guidelines * T2DM participants to be on a stable anti-hyperglycemic regimen with no new drug or drug dosage within 8 weeks of study participation. Variations in daily dose of insulin up to 10% are permitted.
Exclusion criteria
* A positive urine drug screen for drugs of abuse or recreational drugs * Pregnant or nursing females * History of abuse of alcohol or illicit drugs * Significant renal or urinary disease within 6 months of study participation * History of malignancy within the past 5 years basal cell carcinoma of the skin or cervical cancer in situ * History of human immunodeficiency virus (HIV) * History of blood dyscrasias or any disorders causing hemolysis or unstable red blood cells * Any acute disease state (eg, , vomiting, fever, diarrhea) within 7 days before study participation * Treatment with an investigational drug within 30 days of study participation * Use of herbal supplements within 28 days prior to study participation * Any clinically significant malabsorption condition * Blood donation (excluding plasma donations) of approximately 1 pint within 56 days prior to study participation * History of sensitivity to ertugliflozin or other Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors * History of sensitivity to heparin or heparin-induced thrombocytopenia * Unwilling or unable to comply with the study Lifestyle Guidelines * 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 * Use of prescription drugs (hormonal methods of birth control are allowed), vitamins and dietary supplements within 7 days of study participation * For T2DM participants, history of type 1 diabetes mellitus or a history of ketoacidosis * For T2DM participants, clinically significant electrocardiogram abnormality * For T2DM participants, history of myocardial infarction, unstable angina, coronary revascularization, stroke or transient ischemic attack within 3 months of study participation * For T2DM participants, heart failure defined as New York Heart Association Functional Class III-IV * For T2DM participants, renal allograft recipients * For T2DM participants, requiring dialysis * For T2DM participants, strict fluid restriction * For T2DM participants, urinary incontinence * For T2DM participants, acute renal disease * For T2DM participants, significant hepatic, cardiac, or pulmonary disease or clinically nephrotic * For T2DM participants, prescription and over-the-counter medication that is not taken according to a stable regimen for 7 days before study participation * For T2DM participants, on metformin should not be enrolled if their baseline renal function is outside the approved product labeling * For T2DM participants receiving any of the following medications within 7 days of study participation: 1. Other SGLT2 inhibitors (eg, dapagliflozin, canagliflozin, empagliflozin); 2. Other injectable anti-hyperglycemic agents including pramlintide or Glucagon-like peptide-1 (GLP-1) analogues; 3. Any immunosuppressive drugs, including cyclosporine, tacrolimus, sirolimus; 4. Oral corticosteroids (note that inhaled, nasal and topical corticosteroids are permitted); 5. Any potent drug-metabolizing enzyme-inducing drug, including rifampin, phenytoin, and carbamazepine; 6. Probenecid, valproic acid, gemfibrozil.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24 Hour Fluid Balance | For 24 hours before Baseline (-48 to -24 hours) and up to 24 hours after dosing on Day 1 (Up to 24 hours) | Fluid balance = fluid intake - urine output. |
| Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent. |
| Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent. |
| Apparent Clearance (CL/F) for Plasma Ertugliflozin | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent. |
| Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent. |
| Time for Cmax (Tmax) for Plasma Ertugliflozin | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. |
| Terminal Half-Life (t1/2) for Plasma Ertugliflozin | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. |
| Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | VzF is the apparent volume of distribution during terminal phase after oral / extravascular administration. VzF = Dose/(AUCinf × kel) where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent. |
| Unbound Fraction (Fu) for Plasma Ertugliflozin | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Fraction of unbound (not protein-bound) drug in plasma. Fu is determined using in vitro equilibrium dialysis method: concentration in buffer at equilibrium/concentration in plasma at equilibrium. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. |
| Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1 | Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of \[urine concentration × sample volume\] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent. |
| Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%) | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1 | Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96% = Ae96 / Dose × 100 Ae96 = Sum of \[urine concentration × sample volume\] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent. |
| Renal Clearance (CLr) for Urinary Ertugliflozin | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1 | Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Geometric Coefficient of Variation was reported as a percent. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to 19 days | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
| Number of Participants Who Discontinued Study Due to an AE | Up to 5 days | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
| Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf) | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent. |
| Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent. |
| Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944 | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent. |
| Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944 | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. |
| Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944 | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. |
| Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944 | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1 | Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of \[urine concentration × sample volume\] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent. |
| CLr for Urinary Glucuronide Metabolite PF-06481944 | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1 | Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Geometric Coefficient of Variation was reported as a percent. |
| Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf) | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent. |
| Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent. |
| Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948 | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent. |
| Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948 | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. |
| Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948 | Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose | T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. |
| Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948 | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1 | Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of \[urine concentration × sample volume\] for each collection interval from 0 to 96 hours post dose. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent. |
| Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948 | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1 | Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent. |
| Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption | Baseline and 24 Hours | Inhibition of Glucose Reabsorption = 100 \* urinary glucose excretion / (eGFR(ML/MIN) \* Weighted Mean Plasma Glucose \* 0.0144). 0.0144 is a unit conversion factor used to make the ratio unitless. Geometric Coefficient of Variation was reported as a percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin | 0-4, 4-8, 8-12, 12-24 hours after dosing on Day 1 | Participants were asked to void at the end of each prescribed interval with forced voids prior to start and at the end of each interval. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) Ertugliflozin (15 mg), oral, administered in participants with T2DM and with normal renal function | 6 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) Ertugliflozin (15 mg), oral, administered in participants with T2DM and with mild renal impairment | 8 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) Ertugliflozin (15 mg), oral, administered in participants with T2DM and with moderate renal impairment | 8 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) Ertugliflozin (15 mg), oral, administered in participants with T2DM and with severe renal impairment | 6 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) Ertugliflozin (15 mg), oral, administered in participants with healthy participants and with normal renal function | 8 |
| Total | 36 |
Baseline characteristics
| Characteristic | Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 63.2 Years FULL_RANGE 3.5 | 66.4 Years FULL_RANGE 2.4 | 65.8 Years FULL_RANGE 7.9 | 61.2 Years FULL_RANGE 10.3 | 64.3 Years FULL_RANGE 3.9 | 64.4 Years |
| Baseline eGFR | 92.1 mL/min/1.73 m² FULL_RANGE 14.1 | 64.7 mL/min/1.73 m² FULL_RANGE 7.52 | 37.1 mL/min/1.73 m² FULL_RANGE 6.92 | 17.0 mL/min/1.73 m² FULL_RANGE 7.51 | 88.5 mL/min/1.73 m² FULL_RANGE 11.64 | 60.5 mL/min/1.73 m² |
| Baseline Fluid Balance | -644.0 Milliliters FULL_RANGE 668.11 | -274.8 Milliliters FULL_RANGE 570.44 | 238.8 Milliliters FULL_RANGE 763.1 | -267.5 Milliliters FULL_RANGE 430.85 | -359.5 Milliliters FULL_RANGE 693.65 | -243.1 Milliliters |
| Baseline Inhibition of Glucose Readsorption | 2.7 Percentage FULL_RANGE 3.45 | 0.1 Percentage FULL_RANGE 5.17 | 0.3 Percentage FULL_RANGE 1.05 | 3.3 Percentage FULL_RANGE 19.42 | 0.0 Percentage FULL_RANGE 0.02 | 1.1 Percentage |
| Baseline Urinary Glucose Excretion (UGE) | 8.2 Grams FULL_RANGE 10.49 | 0.1 Grams FULL_RANGE 10.21 | 0.2 Grams FULL_RANGE 0.93 | 2.3 Grams FULL_RANGE 3.44 | 0.1 Grams FULL_RANGE 0.04 | 1.8 Grams |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 4 Participants | 0 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 4 Participants | 6 Participants | 5 Participants | 23 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 2 / 8 | 1 / 8 | 3 / 6 | 4 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Apparent Clearance (CL/F) for Plasma Ertugliflozin
CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Apparent Clearance (CL/F) for Plasma Ertugliflozin | 208.8 mL/min | Geometric Coefficient of Variation 42 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Apparent Clearance (CL/F) for Plasma Ertugliflozin | 130.9 mL/min | Geometric Coefficient of Variation 28 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Apparent Clearance (CL/F) for Plasma Ertugliflozin | 120.4 mL/min | Geometric Coefficient of Variation 19 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Apparent Clearance (CL/F) for Plasma Ertugliflozin | 132.0 mL/min | Geometric Coefficient of Variation 23 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Apparent Clearance (CL/F) for Plasma Ertugliflozin | 202.1 mL/min | Geometric Coefficient of Variation 27 |
Primary
Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin
VzF is the apparent volume of distribution during terminal phase after oral / extravascular administration. VzF = Dose/(AUCinf × kel) where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Vz/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin | 239.7 Liters | Geometric Coefficient of Variation 53 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin | 254.5 Liters | Geometric Coefficient of Variation 50 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin | 228.3 Liters | Geometric Coefficient of Variation 27 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin | 268.8 Liters | Geometric Coefficient of Variation 41 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin | 304.5 Liters | Geometric Coefficient of Variation 39 |
Primary
Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf)
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for AUCinf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) | 1199 ng•hr/mL | Geometric Coefficient of Variation 42 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) | 1908 ng•hr/mL | Geometric Coefficient of Variation 28 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) | 2075 ng•hr/mL | Geometric Coefficient of Variation 19 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) | 1895 ng•hr/mL | Geometric Coefficient of Variation 23 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) | 1236 ng•hr/mL | Geometric Coefficient of Variation 27 |
90% CI: [80.32, 132.27]
90% CI: [127.83, 191.23]
90% CI: [139.02, 207.98]
90% CI: [124.38, 193.8]
Primary
Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for AUClast.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 1174 ng•hr/mL | Geometric Coefficient of Variation 42 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 1814 ng•hr/mL | Geometric Coefficient of Variation 27 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 2011 ng•hr/mL | Geometric Coefficient of Variation 18 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 1816 ng•hr/mL | Geometric Coefficient of Variation 23 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 1214 ng•hr/mL | Geometric Coefficient of Variation 27 |
90% CI: [80.66, 132.61]
90% CI: [124.05, 185.34]
90% CI: [137.53, 205.49]
90% CI: [121.69, 189.36]
Primary
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf)
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for AUCinf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf) | 1559 ng•hr/mL | Geometric Coefficient of Variation 21 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf) | 2620 ng•hr/mL | Geometric Coefficient of Variation 34 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf) | 3668 ng•hr/mL | Geometric Coefficient of Variation 56 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf) | 2742 ng•hr/mL | Geometric Coefficient of Variation 41 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf) | 1113 ng•hr/mL | Geometric Coefficient of Variation 32 |
Primary
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for AUClast.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 1536 ng•hr/mL | Geometric Coefficient of Variation 21 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 2517 ng•hr/mL | Geometric Coefficient of Variation 32 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 3552 ng•hr/mL | Geometric Coefficient of Variation 55 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 2642 ng•hr/mL | Geometric Coefficient of Variation 40 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 1090 ng•hr/mL | Geometric Coefficient of Variation 33 |
Primary
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf)
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for AUCinf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf) | 383.9 ng•hr/mL | Geometric Coefficient of Variation 26 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf) | 604.1 ng•hr/mL | Geometric Coefficient of Variation 39 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf) | 950.9 ng•hr/mL | Geometric Coefficient of Variation 75 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf) | 975.0 ng•hr/mL | Geometric Coefficient of Variation 53 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf) | 337.6 ng•hr/mL | Geometric Coefficient of Variation 27 |
Primary
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for AUClast.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 371.9 ng•hr/mL | Geometric Coefficient of Variation 27 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 579.8 ng•hr/mL | Geometric Coefficient of Variation 37 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 917.7 ng•hr/mL | Geometric Coefficient of Variation 74 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 922.1 ng•hr/mL | Geometric Coefficient of Variation 51 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | 329.1 ng•hr/mL | Geometric Coefficient of Variation 28 |
Primary
Change From Baseline in 24 Hour Fluid Balance
Fluid balance = fluid intake - urine output.
Time frame: For 24 hours before Baseline (-48 to -24 hours) and up to 24 hours after dosing on Day 1 (Up to 24 hours)
Population: The analysis population was defined as all treated participants who had at least one measurement for fluid balance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Change From Baseline in 24 Hour Fluid Balance | -660.67 Milliliters | Standard Deviation 515.48 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Change From Baseline in 24 Hour Fluid Balance | -937.00 Milliliters | Standard Deviation 539.14 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Change From Baseline in 24 Hour Fluid Balance | -696.38 Milliliters | Standard Deviation 832.57 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Change From Baseline in 24 Hour Fluid Balance | 111.50 Milliliters | Standard Deviation 736.79 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Change From Baseline in 24 Hour Fluid Balance | -478.63 Milliliters | Standard Deviation 583.02 |
Primary
Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption
Inhibition of Glucose Reabsorption = 100 \* urinary glucose excretion / (eGFR(ML/MIN) \* Weighted Mean Plasma Glucose \* 0.0144). 0.0144 is a unit conversion factor used to make the ratio unitless. Geometric Coefficient of Variation was reported as a percent.
Time frame: Baseline and 24 Hours
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for plasma glucose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption | 33.34 Percentage | Geometric Coefficient of Variation 22 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption | 25.58 Percentage | Geometric Coefficient of Variation 77 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption | 28.84 Percentage | Geometric Coefficient of Variation 34 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption | 24.25 Percentage | Geometric Coefficient of Variation 61 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption | 29.19 Percentage | Geometric Coefficient of Variation 34 |
95% CI: [48.58, 121.19]
95% CI: [54.78, 136.65]
95% CI: [44.63, 118.58]
Primary
CLr for Urinary Glucuronide Metabolite PF-06481944
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Geometric Coefficient of Variation was reported as a percent.
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for CLr.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | CLr for Urinary Glucuronide Metabolite PF-06481944 | 76.28 mL/min. | Geometric Coefficient of Variation 24 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | CLr for Urinary Glucuronide Metabolite PF-06481944 | 38.73 mL/min. | Geometric Coefficient of Variation 58 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | CLr for Urinary Glucuronide Metabolite PF-06481944 | 17.67 mL/min. | Geometric Coefficient of Variation 56 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | CLr for Urinary Glucuronide Metabolite PF-06481944 | 10.27 mL/min. | Geometric Coefficient of Variation 80 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | CLr for Urinary Glucuronide Metabolite PF-06481944 | 94.53 mL/min. | Geometric Coefficient of Variation 25 |
Primary
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96)
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of \[urine concentration × sample volume\] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Ae96.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) | 0.1494 Milligrams | Geometric Coefficient of Variation 55 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) | 0.1081 Milligrams | Geometric Coefficient of Variation 54 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) | 0.09682 Milligrams | Geometric Coefficient of Variation 21 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) | 0.05843 Milligrams | Geometric Coefficient of Variation 40 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) | 0.1231 Milligrams | Geometric Coefficient of Variation 48 |
Primary
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of \[urine concentration × sample volume\] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Ae96.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944 | 7.056 Milligrams | Geometric Coefficient of Variation 32 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944 | 5.861 Milligrams | Geometric Coefficient of Variation 36 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944 | 3.768 Milligrams | Geometric Coefficient of Variation 40 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944 | 1.630 Milligrams | Geometric Coefficient of Variation 41 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944 | 6.225 Milligrams | Geometric Coefficient of Variation 32 |
Primary
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of \[urine concentration × sample volume\] for each collection interval from 0 to 96 hours post dose. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Ae96.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948 | 0.9575 Milligrams | Geometric Coefficient of Variation 45 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948 | 0.7882 Milligrams | Geometric Coefficient of Variation 33 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948 | 0.6603 Milligrams | Geometric Coefficient of Variation 49 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948 | 0.3195 Milligrams | Geometric Coefficient of Variation 43 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948 | 0.8287 Milligrams | Geometric Coefficient of Variation 40 |
Primary
Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin | 215.9 ng/mL | Geometric Coefficient of Variation 35 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin | 313.1 ng/mL | Geometric Coefficient of Variation 30 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin | 305.7 ng/mL | Geometric Coefficient of Variation 23 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin | 196.4 ng/mL | Geometric Coefficient of Variation 28 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin | 219.3 ng/mL | Geometric Coefficient of Variation 26 |
90% CI: [78.83, 130.87]
90% CI: [117.15, 176.37]
90% CI: [114.4, 172.23]
90% CI: [71.99, 112.96]
Primary
Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944 | 217.8 ng/mL | Geometric Coefficient of Variation 18 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944 | 309.0 ng/mL | Geometric Coefficient of Variation 30 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944 | 358.5 ng/mL | Geometric Coefficient of Variation 28 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944 | 218.6 ng/mL | Geometric Coefficient of Variation 33 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944 | 168.6 ng/mL | Geometric Coefficient of Variation 34 |
Primary
Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948 | 44.44 ng/mL | Geometric Coefficient of Variation 22 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948 | 53.56 ng/mL | Geometric Coefficient of Variation 17 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948 | 63.10 ng/mL | Geometric Coefficient of Variation 42 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948 | 46.42 ng/mL | Geometric Coefficient of Variation 35 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948 | 43.90 ng/mL | Geometric Coefficient of Variation 24 |
Primary
Number of Participants Who Discontinued Study Due to an AE
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Up to 5 days
Population: The analysis population was defined as all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Number of Participants Who Discontinued Study Due to an AE | 0 Participants |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Number of Participants Who Discontinued Study Due to an AE | 0 Participants |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Number of Participants Who Discontinued Study Due to an AE | 0 Participants |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Number of Participants Who Discontinued Study Due to an AE | 0 Participants |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Number of Participants Who Discontinued Study Due to an AE | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Up to 19 days
Population: The analysis population was defined as all treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Number of Participants Who Experienced an Adverse Event (AE) | 1 Participants |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
Primary
Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%)
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96% = Ae96 / Dose × 100 Ae96 = Sum of \[urine concentration × sample volume\] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Ae96.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%) | 0.9952 Percent | Geometric Coefficient of Variation 55 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%) | 0.7200 Percent | Geometric Coefficient of Variation 54 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%) | 0.6456 Percent | Geometric Coefficient of Variation 21 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%) | 0.3893 Percent | Geometric Coefficient of Variation 40 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%) | 0.8213 Percent | Geometric Coefficient of Variation 48 |
Primary
Renal Clearance (CLr) for Urinary Ertugliflozin
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Geometric Coefficient of Variation was reported as a percent.
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for CLr.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Renal Clearance (CLr) for Urinary Ertugliflozin | 2.092 mL/min | Geometric Coefficient of Variation 28 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Renal Clearance (CLr) for Urinary Ertugliflozin | 0.9872 mL/min | Geometric Coefficient of Variation 45 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Renal Clearance (CLr) for Urinary Ertugliflozin | 0.8024 mL/min | Geometric Coefficient of Variation 34 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Renal Clearance (CLr) for Urinary Ertugliflozin | 0.5360 mL/min | Geometric Coefficient of Variation 23 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Renal Clearance (CLr) for Urinary Ertugliflozin | 1.682 mL/min | Geometric Coefficient of Variation 33 |
90% CI: [59.41, 108.76]
90% CI: [41.64, 68.63]
90% CI: [33.85, 55.78]
90% CI: [22.04, 38.21]
Primary
Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for CLr.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948 | 41.82 mL/min | Geometric Coefficient of Variation 24 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948 | 22.50 mL/min | Geometric Coefficient of Variation 45 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948 | 11.95 mL/min | Geometric Coefficient of Variation 49 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948 | 5.778 mL/min | Geometric Coefficient of Variation 43 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948 | 41.42 mL/min | Geometric Coefficient of Variation 31 |
Primary
Terminal Half-Life (t1/2) for Plasma Ertugliflozin
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for t1/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Terminal Half-Life (t1/2) for Plasma Ertugliflozin | 14.62 Hours | Standard Deviation 6.37 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Terminal Half-Life (t1/2) for Plasma Ertugliflozin | 25.94 Hours | Standard Deviation 13.98 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Terminal Half-Life (t1/2) for Plasma Ertugliflozin | 22.89 Hours | Standard Deviation 7.35 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Terminal Half-Life (t1/2) for Plasma Ertugliflozin | 24.17 Hours | Standard Deviation 5.98 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Terminal Half-Life (t1/2) for Plasma Ertugliflozin | 17.71 Hours | Standard Deviation 3.53 |
Primary
Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for t1/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944 | 16.68 Hours | Standard Deviation 9.46 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944 | 22.04 Hours | Standard Deviation 12.15 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944 | 23.33 Hours | Standard Deviation 6.15 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944 | 22.83 Hours | Standard Deviation 5.92 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944 | 17.51 Hours | Standard Deviation 5.69 |
Primary
Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for t1/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948 | 14.87 Hours | Standard Deviation 7.77 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948 | 21.71 Hours | Standard Deviation 11.26 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948 | 22.49 Hours | Standard Deviation 5.3 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948 | 25.22 Hours | Standard Deviation 10.42 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948 | 15.68 Hours | Standard Deviation 4.66 |
Primary
Time for Cmax (Tmax) for Plasma Ertugliflozin
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Time for Cmax (Tmax) for Plasma Ertugliflozin | 1.00 Hours |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Time for Cmax (Tmax) for Plasma Ertugliflozin | 1.50 Hours |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Time for Cmax (Tmax) for Plasma Ertugliflozin | 1.50 Hours |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Time for Cmax (Tmax) for Plasma Ertugliflozin | 1.51 Hours |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Time for Cmax (Tmax) for Plasma Ertugliflozin | 1.00 Hours |
Primary
Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944 | 2.00 Hours |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944 | 2.00 Hours |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944 | 3.00 Hours |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944 | 3.00 Hours |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944 | 2.00 Hours |
Primary
Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948 | 2.00 Hours |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948 | 3.00 Hours |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948 | 4.00 Hours |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948 | 3.51 Hours |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948 | 2.00 Hours |
Primary
Unbound Fraction (Fu) for Plasma Ertugliflozin
Fraction of unbound (not protein-bound) drug in plasma. Fu is determined using in vitro equilibrium dialysis method: concentration in buffer at equilibrium/concentration in plasma at equilibrium. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for Fu.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Unbound Fraction (Fu) for Plasma Ertugliflozin | 0.03437 Percent of Unbound Drug | Standard Deviation 0.0011219 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Unbound Fraction (Fu) for Plasma Ertugliflozin | 0.03458 Percent of Unbound Drug | Standard Deviation 0.0027696 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Unbound Fraction (Fu) for Plasma Ertugliflozin | 0.03804 Percent of Unbound Drug | Standard Deviation 0.0021287 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Unbound Fraction (Fu) for Plasma Ertugliflozin | 0.04107 Percent of Unbound Drug | Standard Deviation 0.0036621 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Unbound Fraction (Fu) for Plasma Ertugliflozin | 0.03484 Percent of Unbound Drug | Standard Deviation 0.0014822 |
Secondary
Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin
Participants were asked to void at the end of each prescribed interval with forced voids prior to start and at the end of each interval.
Time frame: 0-4, 4-8, 8-12, 12-24 hours after dosing on Day 1
Population: The analysis population was defined as all treated participants who had at least one concentration measurement for UGE0-24hr.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ertugliflozin 15 mg (T2DM With Normal Renal Function) | Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin | 72.31 Grams | Geometric Coefficient of Variation 30 |
| Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) | Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin | 35.98 Grams | Geometric Coefficient of Variation 113 |
| Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) | Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin | 27.55 Grams | Geometric Coefficient of Variation 68 |
| Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) | Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin | 10.09 Grams | Geometric Coefficient of Variation 57 |
| Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) | Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin | 46.33 Grams | Geometric Coefficient of Variation 31 |
90% CI: [27.22, 90.93]
90% CI: [20.85, 69.64]
90% CI: [7.32, 26.58]