Type 2 Diabetes Mellitus
Conditions
Brief summary
This study will evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of ertugliflozin following oral administration of unlabeled ertugliflozin (MK-8835) and intravenous (IV) and oral administration of 14\^C-labeled ertugliflozin in healthy male participants.
Interventions
DRUGUnlabeled ertugliflozin for oral use
15 mg oral (3 x 5 mg tablets)
DRUG14^C-labeled ertugliflozin for IV use
100 µg (10 µg/mL solution IV) containing approximately 400 nCi 14\^C (ie, radiolabeled ertugliflozin)
DRUG14^C-labeled ertugliflozin for oral use
100 µg (10 µg/mL solution oral) containing approximately 400 nCi 14\^C (ie, radiolabeled ertugliflozin)
Sponsors
Pfizer
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects between the ages of 18 and 65 years. * Body Mass Index (BMI) of 17.5 to 30.5 kg/m\^2; and a total body weight \>50 kg (110 lbs.)
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies). * Any clinically significant malabsorption condition (eg, gastrectomy, bowel resection). * A positive urine drug screen for drugs of abuse or recreational drugs. * Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results. * History of abuse of alcohol or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. * Current smokers and those who have smoked any substance within the last 12 months. * Treatment with an investigational drug within 1 month preceding the first dose of study medication. * Have participated in any clinical study with exposure to 14\^C in the last 12 months. * Any radiation exposure, including that which is projected to result from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures. No occupationally exposed worker, as defined in the Ionising Radiation Regulation 1999, shall participate in the study. * Use of prescription or nonprescription drugs (including vitamins and dietary supplements) within 7 days prior to the first dose of study medication. * Use of herbal supplements within 28 days prior to the first dose of study medication. * Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing. * Participants who have previously participated in a clinical trial for ertugliflozin. * Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUC Last) (Dose Normalized to 1 mg) and Absolute Oral Bioavailability (F) (Period 1) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | AUC0-inf is a measure of the mean concentration levels of drug in the plasma after the drug dose. An absolute bioavailability provides information on the amount of a drug reaching the systemic circulation and can be determined by comparing the plasma concentration-time-curves (area under the curve) of a compound after oral application of that compound to that after intravenous application of the same compound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter: (AUC Inf) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | AUC0-inf is a measure of the mean concentration levels of drug in the plasma after the dose. Geometric coefficient of variation is given as the percent coefficient of variation. |
| Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) (Dose Normalized to 1 mg) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Geometric coefficient of variation is given as the percent coefficient of variation. |
| Pharmacokinetic Parameter: Time for Cmax (Tmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. The confidence intervals displayed are minimums to maximums. |
| Pharmacokinetic Parameter: Terminal Elimination Half-Life (t1/2) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. |
| Pharmacokinetic Parameter: Apparent Oral Total Plasma Clearance (CL/F) - Oral, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | Apparent clearance is a calculation of the rate at which a drug is removed from plasma after oral administration via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). Geometric coefficient of variation is given as the percent coefficient of variation. This outcome measure is for the Ertugliflozin oral drug profile only so no participants were analyzed in the 14\^C-Ertugliflozin 100 ug IV arm. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUC Last) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ert. 100 ug IV (Period 1) (Dose Not Normalized to 1 mg) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | AUC0-last is a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration. Geometric coefficient of variation is given as the percent coefficient of variation. |
| Pharmacokinetic Parameter: Apparent Volume of Distribution (Vz/F) Following Oral Administration - Oral, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed. Geometric coefficient of variation is given as the percent coefficient of variation. This outcome measure is for the Ertugliflozin oral drug profile only so no participants were analyzed in the 14\^C-Ertugliflozin 100 ug intravneous arm. |
| Pharmacokinetic Parameter: Steady-State Volume of Distribution (Vss) Following IV Infusion - IV, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | Steady-State Volume of Distribution is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state. Geometric coefficient of variation is given as the percent coefficient of variation. This outcome measure is for the Ertugliflozin intravenous drug profile only so no participants were analyzed in the Ertugliflozin oral arm. |
| Pharmacokinetic Parameter: Fraction Absorbed (Fa, Radioactivity in Urine) (Periods 1 and 2) (Dose Normalized) | Part 1: pre- IV dose, 0-11 and 11-23 hrs. post IV dose, and 23 - 47, 47 - 71 and 71 - 95 hrs. until Day 5; Part 2: predose, 0-12 and 12-24 hrs. post dose, and then 24-hour intervals until Day 5 | Fraction absorbed is the fraction of the total ertugliflozin dose absorbed, regardless of the fate of that dose after absorption (i.e., metabolism, degradation, etc). Fraction Absorbed was estimated as the ratio of total radioactivity (dose normalized) excreted into the urine (from time zero to the time of last measurable concentration) following oral and IV administration of 14\^C-ertugliflozin. Fraction of 14\^C dose recovered in urine = 14\^C total in urine in dpm/14\^C total in dose in dpm |
| Number of Participants Who Experienced an Adverse Event (Periods 1 and 2) | Up to approximately 33 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 Discontinuing Study Drug Due to Adverse Events (Periods 1 and 2) | Up to approximately 16 days | An 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. |
| Pharmacokinetic Parameter: Systemic IV Total Plasma Clearance (CL) - IV, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion | Systemic clearance is a calculation of the rate at which a drug is removed from plasma via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). Geometric coefficient of variation is given as the percent coefficient of variation. This outcome measure is for the Ertugliflozin intravenous drug profile only so no participants were analyzed in the Ertugliflozin oral arm. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ertugliflozin Period 1: Oral dose of 15 mg unlabeled ertugliflozin + intravenous (IV) dose of 100 µg 14\^C-labeled ertugliflozin containing approximately 400 nCi 14\^C. The 14\^C IV dose will be administered as an infusion over approximately 5 minutes starting at 55 minutes after the unlabeled oral dose. → Period 2: Oral dose 15 mg unlabeled ertugliflozin + oral dose of 100 µg 14\^C-labeled ertugliflozin containing approximately 400 nCi 14\^C. Both the unlabeled and 14\^C-ertugliflozin will be administered at the same time (no more than 5 minutes apart). Dosing in Periods 1 and 2 will be separated by a washout of at least 11 days. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Ertugliflozin |
|---|---|
| Age, Continuous | 41.0 Years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUC Last) (Dose Normalized to 1 mg) and Absolute Oral Bioavailability (F) (Period 1)
AUC0-inf is a measure of the mean concentration levels of drug in the plasma after the drug dose. An absolute bioavailability provides information on the amount of a drug reaching the systemic circulation and can be determined by comparing the plasma concentration-time-curves (area under the curve) of a compound after oral application of that compound to that after intravenous application of the same compound.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The pharmacokinetic (PK) Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUC Last) (Dose Normalized to 1 mg) and Absolute Oral Bioavailability (F) (Period 1) | 93.16 AUCinf(dn), ng•hr/mL/mg | Geometric Coefficient of Variation 13 |
| 14^C-Ertugliflozin 100 ug IV | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUC Last) (Dose Normalized to 1 mg) and Absolute Oral Bioavailability (F) (Period 1) | 88.96 AUCinf(dn), ng•hr/mL/mg | Geometric Coefficient of Variation 15 |
Comparison: Ratio - Test (oral) / Reference (IV) of means90% CI: [101.64, 107.91]
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUC Last) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ert. 100 ug IV (Period 1) (Dose Not Normalized to 1 mg)
AUC0-last is a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration. Geometric coefficient of variation is given as the percent coefficient of variation.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUC Last) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ert. 100 ug IV (Period 1) (Dose Not Normalized to 1 mg) | 1376 ng•hr/mL | Geometric Coefficient of Variation 12 |
| 14^C-Ertugliflozin 100 ug IV | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUC Last) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ert. 100 ug IV (Period 1) (Dose Not Normalized to 1 mg) | 7.859 ng•hr/mL | Geometric Coefficient of Variation 14 |
Secondary
Number of Participants Discontinuing Study Drug Due to Adverse Events (Periods 1 and 2)
An 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 approximately 16 days
Population: The Safety Population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Number of Participants Discontinuing Study Drug Due to Adverse Events (Periods 1 and 2) | 0 Participants |
| 14^C-Ertugliflozin 100 ug IV | Number of Participants Discontinuing Study Drug Due to Adverse Events (Periods 1 and 2) | 0 Participants |
Secondary
Number of Participants Who Experienced an Adverse Event (Periods 1 and 2)
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 approximately 33 days
Population: The Safety Population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Number of Participants Who Experienced an Adverse Event (Periods 1 and 2) | 3 Participants |
| 14^C-Ertugliflozin 100 ug IV | Number of Participants Who Experienced an Adverse Event (Periods 1 and 2) | 1 Participants |
Secondary
Pharmacokinetic Parameter: Apparent Oral Total Plasma Clearance (CL/F) - Oral, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
Apparent clearance is a calculation of the rate at which a drug is removed from plasma after oral administration via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). Geometric coefficient of variation is given as the percent coefficient of variation. This outcome measure is for the Ertugliflozin oral drug profile only so no participants were analyzed in the 14\^C-Ertugliflozin 100 ug IV arm.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Pharmacokinetic Parameter: Apparent Oral Total Plasma Clearance (CL/F) - Oral, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 178.7 mL/min. | Geometric Coefficient of Variation 13 |
Secondary
Pharmacokinetic Parameter: Apparent Volume of Distribution (Vz/F) Following Oral Administration - Oral, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed. Geometric coefficient of variation is given as the percent coefficient of variation. This outcome measure is for the Ertugliflozin oral drug profile only so no participants were analyzed in the 14\^C-Ertugliflozin 100 ug intravneous arm.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Pharmacokinetic Parameter: Apparent Volume of Distribution (Vz/F) Following Oral Administration - Oral, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 215.3 Liters | Geometric Coefficient of Variation 21 |
Secondary
Pharmacokinetic Parameter: (AUC Inf) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
AUC0-inf is a measure of the mean concentration levels of drug in the plasma after the dose. Geometric coefficient of variation is given as the percent coefficient of variation.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Pharmacokinetic Parameter: (AUC Inf) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 1397 ng•hr/mL | Geometric Coefficient of Variation 13 |
| 14^C-Ertugliflozin 100 ug IV | Pharmacokinetic Parameter: (AUC Inf) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 8.477 ng•hr/mL | Geometric Coefficient of Variation 15 |
Secondary
Pharmacokinetic Parameter: Fraction Absorbed (Fa, Radioactivity in Urine) (Periods 1 and 2) (Dose Normalized)
Fraction absorbed is the fraction of the total ertugliflozin dose absorbed, regardless of the fate of that dose after absorption (i.e., metabolism, degradation, etc). Fraction Absorbed was estimated as the ratio of total radioactivity (dose normalized) excreted into the urine (from time zero to the time of last measurable concentration) following oral and IV administration of 14\^C-ertugliflozin. Fraction of 14\^C dose recovered in urine = 14\^C total in urine in dpm/14\^C total in dose in dpm
Time frame: Part 1: pre- IV dose, 0-11 and 11-23 hrs. post IV dose, and 23 - 47, 47 - 71 and 71 - 95 hrs. until Day 5; Part 2: predose, 0-12 and 12-24 hrs. post dose, and then 24-hour intervals until Day 5
Population: The estimated Fa Population included only the 6 participants with complete urine data for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Pharmacokinetic Parameter: Fraction Absorbed (Fa, Radioactivity in Urine) (Periods 1 and 2) (Dose Normalized) | 0.432 Fraction of 14^C dose recovered in urine | Geometric Coefficient of Variation 10 |
| 14^C-Ertugliflozin 100 ug IV | Pharmacokinetic Parameter: Fraction Absorbed (Fa, Radioactivity in Urine) (Periods 1 and 2) (Dose Normalized) | 0.390 Fraction of 14^C dose recovered in urine | Geometric Coefficient of Variation 19 |
Comparison: Ratio - Test (Oral) / Reference (IV) (%)
Secondary
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) (Dose Normalized to 1 mg)
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Geometric coefficient of variation is given as the percent coefficient of variation.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) (Dose Normalized to 1 mg) | 17.09 ng/mL/mg | Geometric Coefficient of Variation 14 |
| 14^C-Ertugliflozin 100 ug IV | Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) (Dose Normalized to 1 mg) | 89.34 ng/mL/mg | Geometric Coefficient of Variation 32 |
Secondary
Pharmacokinetic Parameter: Steady-State Volume of Distribution (Vss) Following IV Infusion - IV, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
Steady-State Volume of Distribution is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state. Geometric coefficient of variation is given as the percent coefficient of variation. This outcome measure is for the Ertugliflozin intravenous drug profile only so no participants were analyzed in the Ertugliflozin oral arm.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 14^C-Ertugliflozin 100 ug IV | Pharmacokinetic Parameter: Steady-State Volume of Distribution (Vss) Following IV Infusion - IV, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 85.53 Liters | Geometric Coefficient of Variation 15 |
Secondary
Pharmacokinetic Parameter: Systemic IV Total Plasma Clearance (CL) - IV, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
Systemic clearance is a calculation of the rate at which a drug is removed from plasma via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). Geometric coefficient of variation is given as the percent coefficient of variation. This outcome measure is for the Ertugliflozin intravenous drug profile only so no participants were analyzed in the Ertugliflozin oral arm.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 14^C-Ertugliflozin 100 ug IV | Pharmacokinetic Parameter: Systemic IV Total Plasma Clearance (CL) - IV, Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 187.2 mL/min. | Geometric Coefficient of Variation 15 |
Secondary
Pharmacokinetic Parameter: Terminal Elimination Half-Life (t1/2) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Pharmacokinetic Parameter: Terminal Elimination Half-Life (t1/2) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 14.04 Hours | Standard Deviation 2.17 |
| 14^C-Ertugliflozin 100 ug IV | Pharmacokinetic Parameter: Terminal Elimination Half-Life (t1/2) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 8.098 Hours | Standard Deviation 2.248 |
Secondary
Pharmacokinetic Parameter: Time for Cmax (Tmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. The confidence intervals displayed are minimums to maximums.
Time frame: Oral: 0, 15 and 30 min., and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hrs. after oral dose; IV: -5 min. (predose), 0 (end of infusion), and at 10, 20, 30, and 45 min. and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 11, 23, 47, 71, and 95 hrs. after end of infusion
Population: The PK Parameter Analysis Population for ertugliflozin is defined as all participants treated who have at least 1 of the ertugliflozin PK parameters of interest. The PK Parameter Analysis Population for 14\^C-ertugliflozin analysis is defined as all participants treated who have at least 1 of the 14\^C parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Unlabeled Ertugliflozin 15 mg Oral | Pharmacokinetic Parameter: Time for Cmax (Tmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 1.00 Hours |
| 14^C-Ertugliflozin 100 ug IV | Pharmacokinetic Parameter: Time for Cmax (Tmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1) | 0.083 Hours |