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

20 août 2018 mis à jour par: Merck Sharp & Dohme LLC

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

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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

8

Phase

  • La phase 1

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 65 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Homme

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: Unlabeled ertugliflozin for oral use
15 mg oral (3 x 5 mg tablets)
Médicament: 14^C-labeled ertugliflozin for IV use
100 µg (10 µg/mL solution IV) containing approximately 400 nCi 14^C (ie, radiolabeled ertugliflozin)
Médicament: 14^C-labeled ertugliflozin for oral use
100 µg (10 µg/mL solution oral) containing approximately 400 nCi 14^C (ie, radiolabeled ertugliflozin)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
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)
Délai: 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.
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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
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)
Délai: 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.
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
Pharmacokinetic Parameter: (AUC Inf) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
Délai: 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.
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
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)
Délai: 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.
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
Pharmacokinetic Parameter: Time for Cmax (Tmax) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
Délai: 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.
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
Pharmacokinetic Parameter: Terminal Elimination Half-Life (t1/2) Following Administration of Unlabeled Ertugliflozin 15 mg Oral + 14^C-Ertugliflozin 100 ug IV (Period 1)
Délai: 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%.
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
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)
Délai: 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.
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
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)
Délai: 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.
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
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)
Délai: 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.
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
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)
Délai: 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.
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
Pharmacokinetic Parameter: Fraction Absorbed (Fa, Radioactivity in Urine) (Periods 1 and 2) (Dose Normalized)
Délai: 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
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
Number of Participants Who Experienced an Adverse Event (Periods 1 and 2)
Délai: 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.
Up to approximately 33 days
Number of Participants Discontinuing Study Drug Due to Adverse Events (Periods 1 and 2)
Délai: 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.
Up to approximately 16 days

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Merck Sharp & Dohme LLC

Collaborateurs

Pfizer

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

29 octobre 2014

Achèvement primaire (Réel)

30 janvier 2015

Achèvement de l'étude (Réel)

9 février 2015

Dates d'inscription aux études

Première soumission

3 avril 2015

Première soumission répondant aux critères de contrôle qualité

3 avril 2015

Première publication (Estimation)

8 avril 2015

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

18 septembre 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

20 août 2018

Dernière vérification

1 août 2018

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 8835-020
  • B1521043 (Autre identifiant: Pfizer Protocol Number)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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