Skip to main content
OpenTrials
Completed

NCT Number: NCT02411929

A Phase 1 Study of Ertugliflozin in Healthy Male Participants (MK-8835-020)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Unlabeled ertugliflozin for oral use

Drug

15 mg oral (3 x 5 mg tablets)

14^C-labeled ertugliflozin for IV use

Drug

100 µg (10 µg/mL solution IV) containing approximately 400 nCi 14^C (ie, radiolabeled ertugliflozin)

14^C-labeled ertugliflozin for oral use

Drug

100 µg (10 µg/mL solution oral) containing approximately 400 nCi 14^C (ie, radiolabeled ertugliflozin)

Primary outcomes

  1. 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)

    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

    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 outcomes

  1. 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)

    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

    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.

  2. Pharmacokinetic Parameter: (AUC Inf) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)

    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

    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.

  3. 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)

    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

    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.

  4. Pharmacokinetic Parameter: Time for Cmax (Tmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)

    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

    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.

  5. Pharmacokinetic Parameter: Terminal Elimination Half-Life (t1/2) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)

    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

    T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%.

  6. 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)

    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

    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.

  7. 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)

    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

    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.

  8. 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)

    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

    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.

  9. 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)

    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

    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.

  10. Pharmacokinetic Parameter: Fraction Absorbed (Fa, Radioactivity in Urine) (Periods 1 and 2) (Dose Normalized)

    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

    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

  11. Number of Participants Who Experienced an Adverse Event (Periods 1 and 2)

    Time frame: 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.

  12. Number of Participants Discontinuing Study Drug Due to Adverse Events (Periods 1 and 2)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Collaborators

  • Pfizer

Registry information

Official study title

A Phase 1, Open-Label, Non-Randomized, 2-Period, Fixed Sequence, Study to Assess the Absolute Bioavailability and Fraction Absorbed of Ertugliflozin in Health Male Subjects Using a 14^C-Microdose Approach

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Apr 8, 2015
Registry last updated
Sep 18, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.