A Single Escalating Dose Study Of Ertugliflozin (PF-04971729, MK-8835) Under Fed and Fasted Conditons In Healthy Volunteers (MK-8835-036)

A Phase 1 Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of PF-04971729 After Administration of Single Escalating Oral Doses Under Fed and Fasted Conditions in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Ertugliflozin; Drug: Placebo to Ertugliflozin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

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 at time of dosing)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Sequence 1; 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: Ertugliflozin; Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.; Drug: Placebo to Ertugliflozin; Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
Experimental: Cohort 1 Sequence 2; 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: Ertugliflozin; Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.; Drug: Placebo to Ertugliflozin; Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
Experimental: Cohort 1 Sequence 3; 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: Ertugliflozin; Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.; Drug: Placebo to Ertugliflozin; Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
Experimental: Cohort 2 Sequence 1; 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: Ertugliflozin; Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.; Drug: Placebo to Ertugliflozin; Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
Experimental: Cohort 2 Sequence 2; 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: Ertugliflozin; Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.; Drug: Placebo to Ertugliflozin; Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution
Experimental: Cohort 2 Sequence 3; 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: Ertugliflozin; Ertugliflozin will be administered as an extemporaneously prepared suspension/solution for all doses within the initially planned range.; Drug: Placebo to Ertugliflozin; Correspondingly placebo doses to ertugliflozin will be administered as suspension/solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Pfizer

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2009
• Primary Completion (Actual): December 11, 2009
• Study Completion (Actual): December 11, 2009

Study Registration Dates

• First Submitted: October 1, 2009
• First Submitted That Met QC Criteria: October 1, 2009
• First Posted (Estimate): October 2, 2009

Study Record Updates

• Last Update Posted (Actual): May 29, 2020
• Last Update Submitted That Met QC Criteria: May 28, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Single Ascending Dose Study in healthy subjects
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Ertugliflozin
• Other Study ID Numbers: 8835-036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No