A Multiple Dose Study Of Ertugliflozin (PF-04971729, MK-8835) In Otherwise Healthy Overweight And Obese Volunteers (MK-8835-037)

A Phase 1, Randomized, Placebo-Controlled, Parallel Group, 14 Day Repeated Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of PF-04971729 In Otherwise Healthy Overweight And Obese Adult Subjects

Ertugliflozin (PF-04971729, MK-8835) is under development for the treatment of Type 2 Diabetes. The primary purpose of this trial is to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, of multiple oral doses of ertugliflozin.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Ertugliflozin; Drug: Placebo to Ertugliflozin

Detailed Description

To evaluate the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics, of multiple oral doses of ertugliflozin.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive.

Body Mass Index (BMI) of 26.5 to 35.5 kg/m2; 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 at time of dosing).

Evidence of glycosuria, as defined by a positive urine dipstick test; Fasting (at least 10 hours) serum triglyceride >300 mg/dL; Fasting (at least 10 hours) LDL-cholesterol >190 mg/dL; Fasting (at least 10 hours) serum 25-OH Vitamin D concentration <20 ng/mL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ertugliflozin 1 mg; Ertugliflozin 1 mg, oral, once daily for 14 days	Drug: Ertugliflozin; Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast; Other Names: MK-8835; PF-04971729
EXPERIMENTAL: Ertugliflozin up to 5 mg; Ertugliflozin up to 5 mg, oral, once daily for 14 days	Drug: Ertugliflozin; Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast; Other Names: MK-8835; PF-04971729
EXPERIMENTAL: Ertugliflozin up to 25 mg; Ertugliflozin up to 25 mg, oral, once daily for 14 days	Drug: Ertugliflozin; Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast; Other Names: MK-8835; PF-04971729
EXPERIMENTAL: Ertugliflozin up to 100 mg; Ertugliflozin up to 100 mg, once daily for 14 days	Drug: Ertugliflozin; Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast; Other Names: MK-8835; PF-04971729
PLACEBO_COMPARATOR: Placebo; Placebo to Ertugliflozin once daily for 14 days	Drug: Placebo to Ertugliflozin; Placebo oral dosing solutions/suspensions administered once daily for 14 days immediately after breakfast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Experiencing an Adverse Event (AE)	Up to 28 days postdose (Up to 42 days)
Number of Participants Discontinuing Study Drug Due to an AE	Up to 14 days
Area under the plasma concentration-time curve (AUC) over the dosing interval tau (AUCtau) for ertugliflozin	Up to 17 days
Maximum plasma concentration (Cmax) of ertugliflozin	Up to 17 days
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin	Up to 17 days
Ertugliflozin half life (t1/2)	Up to 17 Days
Apparent clearance (CL/F) after a single dose of ertugliflozin	Up to 17 days
Apparent volume of distribution (Vz/F)	Up to 17 days
Observed Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac[obs])	Up to 17 days
Change from baseline in 24-hour weighted mean glucose	Baseline and Day 14
Change from baseline in 24-hour urinary glucose excretion	Baseline and Day 14
Change from baseline in 24-hour plasma C-peptide	Baseline and Day 14
Inhibition of glucose reabsorption	Baseline and Day 14
Change from baseline in body weight	Baseline and Day 14
Area under the plasma concentration-time curve over 8 hours (AUC[0-8]) for serum intact parathyroid hormone	Up to 17 days
Area under the plasma concentration-time curve over 24 hours (AUC[0-24]) for serum intact parathyroid hormone	Up to 17 days
Trough concentration of serum intact parathyroid hormone (Ctrough)	Up to 17 days

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 14, 2009
• Primary Completion (ACTUAL): March 18, 2010
• Study Completion (ACTUAL): March 18, 2010

Study Registration Dates

• First Submitted: November 23, 2009
• First Submitted That Met QC Criteria: November 23, 2009
• First Posted (ESTIMATE): November 25, 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

• Additional Relevant MeSH Terms: Body Weight; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Ertugliflozin
• Other Study ID Numbers: 8835-037

Plan for Individual participant data (IPD)

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