NCT00989079

Brief Summary

Ertugliflozin (PF-04971729, MK-8835) is a new compound proposed for the treatment of Type 2 diabetes mellitus. The primary purpose of this study is to evaluate the safety and tolerability along with the pharmacokinetics of single escalating doses of ertugliflozin under fed and fasted conditions in healthy volunteers.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for phase_1 type-2-diabetes-mellitus

Timeline
Completed

Started Oct 2009

Shorter than P25 for phase_1 type-2-diabetes-mellitus

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 1, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 2, 2009

Completed
14 days until next milestone

Study Start

First participant enrolled

October 16, 2009

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 11, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 11, 2009

Completed
Last Updated

May 29, 2020

Status Verified

May 1, 2020

Enrollment Period

2 months

First QC Date

October 1, 2009

Last Update Submit

May 28, 2020

Conditions

Type 2 Diabetes Mellitus

Keywords

Single Ascending Dose Study in healthy subjects

Outcome Measures

Primary Outcomes (10)

  • Number of Participants Experiencing an Adverse Event (AE)

    Up to Day 10 of each dosing period

  • Number of Participants Discontinuing Study Drug Due to an AE

    Up to Day 8 of each dosing period

  • Change from baseline in 24-hour urinary glucose excretion

    Baseline and 24 hours

  • Area under the plasma concentration-time curve (AUC) from Time 0 to infinity (AUCinf) for ertugliflozin

    Up to Day 4 of each treatment period

  • Area under the plasma concentration-time curve (AUC) from Time 0 to time of the last quantifiable concentration (AUClast) for ertugliflozin

    Up to Day 4 of each treatment period

  • Maximum plasma concentration (Cmax) of ertugliflozin

    Up to Day 4 of each treatment period

  • Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin

    Up to Day 4 of each treatment period

  • Ertugliflozin half life (t1/2)

    Up to Day 4 of each treatment period

  • Apparent clearance (CL/F) after a single dose of ertugliflozin

    Up to Day 4 of each treatment period

  • Apparent volume of distribution (Vz/F)

    Up to Day 4 of each treatment period

Secondary Outcomes (5)

  • Urinary glucose excretion over 72 hours

    Up to 72 hours of each dosing period

  • Change from baseline in 24-hour weighted mean glucose

    Baseline and 24 hours

  • Inhibition of glucose reabsorption

    Up to 24 hours of each dosing period

  • Renal clearance (CLr) of Ertugliflozin

    Up to 24 hours of each dosing period

  • Urinary recovery of Ertugliflozin

    Up to 24 hours of each dosing period

Study Arms (6)

Cohort 1 Sequence 1

EXPERIMENTAL

Period 1 (fasted) Placebo → Period 2 (fasted) ertugliflozin (E) 10 mg → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.

Drug: ErtugliflozinDrug: Placebo to Ertugliflozin

Cohort 1 Sequence 2

EXPERIMENTAL

Period 1 (fasted) E 0.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.

Drug: ErtugliflozinDrug: Placebo to Ertugliflozin

Cohort 1 Sequence 3

EXPERIMENTAL

Period 1 (fasted) E 0.5 mg → Period 2 (fasted) E 10 mg → Period 3 (fasted) Placebo → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.

Drug: ErtugliflozinDrug: Placebo to Ertugliflozin

Cohort 2 Sequence 1

EXPERIMENTAL

Period 1 (fasted) Placebo → Period 2 (fasted) E 30 mg → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.

Drug: ErtugliflozinDrug: Placebo to Ertugliflozin

Cohort 2 Sequence 2

EXPERIMENTAL

Period 1 (fasted) E 2.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.

Drug: ErtugliflozinDrug: Placebo to Ertugliflozin

Cohort 2 Sequence 3

EXPERIMENTAL

Period 1 (fasted) E 2.5 mg → Period 2 (fasted) E 30 mg → Period 3 (fasted) Placebo. Each dose of study drug will be separated by a minimum of 7 days.

Drug: ErtugliflozinDrug: Placebo to Ertugliflozin

Interventions

ErtugliflozinDRUG

Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.

Cohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Placebo to ErtugliflozinDRUG

Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution

Cohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy male and/or female subjects of non childbearing potential.
  • Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg

You may not qualify if:

  • 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 at time of dosing)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (4)

  • Fediuk DJ, Nucci G, Dawra VK, Cutler DL, Amin NB, Terra SG, Boyd RA, Krishna R, Sahasrabudhe V. Overview of the Clinical Pharmacology of Ertugliflozin, a Novel Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor. Clin Pharmacokinet. 2020 Aug;59(8):949-965. doi: 10.1007/s40262-020-00875-1.

    PMID: 32337660RESULT

  • Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.

    PMID: 34213819DERIVED

  • Marshall JC, Liang Y, Sahasrabudhe V, Tensfeldt T, Fediuk DJ, Zhou S, Krishna R, Dawra VK, Wood LS, Sweeney K. Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure. J Clin Pharmacol. 2021 Sep;61(9):1220-1231. doi: 10.1002/jcph.1866. Epub 2021 Jun 19.

    PMID: 33813736DERIVED

  • Callegari E, Lin J, Tse S, Goosen TC, Sahasrabudhe V. Physiologically-Based Pharmacokinetic Modeling of the Drug-Drug Interaction of the UGT Substrate Ertugliflozin Following Co-Administration with the UGT Inhibitor Mefenamic Acid. CPT Pharmacometrics Syst Pharmacol. 2021 Feb;10(2):127-136. doi: 10.1002/psp4.12581. Epub 2020 Dec 30.

    PMID: 33314761DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Medical Director

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 1, 2009

First Posted

October 2, 2009

Study Start

October 16, 2009

Primary Completion

December 11, 2009

Study Completion

December 11, 2009

Last Updated

May 29, 2020

Record last verified: 2020-05

Data Sharing

IPD Sharing
Will share

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

More information