A Study of the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Participants With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise (MK-8835-003, VERTIS MONO)

September 1, 2017 updated by: Merck Sharp & Dohme LLC

A Phase 3, Randomized, Double-blind, Placebo-controlled, 26-week Multicenter Study With a 26-Week Extension to Evaluate the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise

This trial will evaluate the efficacy and safety of ertugliflozin monotherapy in the treatment of participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on diet and exercise. This trial consists of a run-in period of 3 to 11 weeks, a 26-week placebo-controlled treatment period (Phase A), and a 26-week active treatment period (Phase B). The primary hypotheses of the trial are that at Week 26, the mean reduction from baseline in hemoglobin A1c (A1C) for 15 mg ertugliflozin is greater than that for placebo and the mean reduction from baseline in A1C for 5 mg ertugliflozin is greater than that for placebo.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

461

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of T2DM in accordance to American Diabetes Association guidelines
  • Participants with no prior allowable oral anti-hyperglycemic agents (AHA) for at least 8 weeks prior to study participation or participants on a single allowable oral AHA at the start of study participation
  • Participants on a single allowable AHA must be willing to discontinue this medication at the Screening Visit (S2) and remain off this medication for the duration of the trial. Allowable oral AHAs for discontinuation are metformin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides or alpha-glucosidase inhibitors.

Exclusion Criteria:

  • History of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study participation
  • A clinically significant electrocardiogram abnormality
  • A history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer
  • A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor or metformin
  • On a blood pressure or lipid altering medication that have not been on a stable dose for at least 4 weeks prior to study participation
  • A surgical procedure within 4 weeks prior to study participation or planned major surgery during the trial
  • Donation of blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
  • Pregnant or breast-feeding, or is expecting to conceive during the trial, including 14 days following the last dose of study drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ertugliflozin 5 mg/Ertugliflozin 5 mg
Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
Drug: Ertugliflozin 5 mg
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
  • MK-8835
  • PF-04971729
Drug: Placebo to Ertugliflozin
One placebo tablet matching the ertugliflozin 5 mg tablet and/or 1 placebo tablet matching the ertugliflozin 10 mg tablet per day taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Drug: Metformin
500 mg (1 tablet) in the morning and 500 mg (1 tablet) in the evening for 2 weeks, 1000 mg (2 tablets 500 mg) in the morning and 500 mg (1 tablet) in the evening for 2 weeks and 1000 mg (2 tablets 500 mg) in the morning and 1000 mg (2 tablets 500 mg) in the evening, thereafter.
Other Names:
  • Glucophage XR, Carbophage SR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor and Metfogamma.
Drug: Placebo to Metformin
1 tablet in the morning and 1 tablet in the evening for 2 weeks, 2 tablets in the morning and 1 tablet in the evening for 2 weeks and 2 tablets in the morning and 2 tablets in the evening, thereafter.
Drug: Glimepiride
Dosing and titration of glimepiride as rescue therapy was determined by the investigator.
Experimental: Ertugliflozin 15 mg/Ertugliflozin 15 mg
Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
Drug: Ertugliflozin 5 mg
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
  • MK-8835
  • PF-04971729
Drug: Metformin
500 mg (1 tablet) in the morning and 500 mg (1 tablet) in the evening for 2 weeks, 1000 mg (2 tablets 500 mg) in the morning and 500 mg (1 tablet) in the evening for 2 weeks and 1000 mg (2 tablets 500 mg) in the morning and 1000 mg (2 tablets 500 mg) in the evening, thereafter.
Other Names:
  • Glucophage XR, Carbophage SR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor and Metfogamma.
Drug: Placebo to Metformin
1 tablet in the morning and 1 tablet in the evening for 2 weeks, 2 tablets in the morning and 1 tablet in the evening for 2 weeks and 2 tablets in the morning and 2 tablets in the evening, thereafter.
Drug: Glimepiride
Dosing and titration of glimepiride as rescue therapy was determined by the investigator.
Drug: Ertugliflozin 10 mg
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
  • MK-8835
  • PF-04971729
Other: Placebo/Metformin
Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
Drug: Placebo to Ertugliflozin
One placebo tablet matching the ertugliflozin 5 mg tablet and/or 1 placebo tablet matching the ertugliflozin 10 mg tablet per day taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Drug: Metformin
500 mg (1 tablet) in the morning and 500 mg (1 tablet) in the evening for 2 weeks, 1000 mg (2 tablets 500 mg) in the morning and 500 mg (1 tablet) in the evening for 2 weeks and 1000 mg (2 tablets 500 mg) in the morning and 1000 mg (2 tablets 500 mg) in the evening, thereafter.
Other Names:
  • Glucophage XR, Carbophage SR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor and Metfogamma.
Drug: Glimepiride
Dosing and titration of glimepiride as rescue therapy was determined by the investigator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline In A1C at Week 26
Time Frame: Baseline and Week 26
A1C is measured as percent. The change from baseline is the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
Baseline and Week 26
Percentage of Participants Experiencing An Adverse Event (AE)
Time Frame: Up to 54 weeks (including 2 weeks following last dose)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
Up to 54 weeks (including 2 weeks following last dose)
Percentage of Participants Discontinuing Study Treatment Due to an AE
Time Frame: Up to 52 weeks
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
Up to 52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in FPG at Week 26
Time Frame: Baseline and Week 26
The change from baseline is the Week 26 FPG minus the Week 0 FPG. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of glycemic rescue therapy.
Baseline and Week 26
Change From Baseline in Body Weight at Week 26
Time Frame: Baseline and Week 26
The change from baseline is the Week 26 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy.
Baseline and Week 26
Percentage of Participants With A1C <7% (<53 mmol/Mol) at Week 26
Time Frame: Week 26
A1C is measured as percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
Week 26
Baseline 2-hour Post-prandial Glucose (2-hr PPG) Level
Time Frame: Baseline
Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the Mixed Meal Tolerance Test (MMTT). Change from baseline in 2-hr PPG level at Week 26 data are presented in the following outcome measure.
Baseline
Change From Baseline in 2-hr PPG at Week 26
Time Frame: Baseline and Week 26
The change from baseline is the Week 26 2-hr PPG minus the Week 0 2-hr PPG. Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the MMTT. Data presented exclude data following the initiation of rescue therapy.
Baseline and Week 26
Baseline Sitting Systolic Blood Pressure (SBP)
Time Frame: Baseline
Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in SBP at Week 26 data are presented in the following outcome measure.
Baseline
Change From Baseline in SBP at Week 26
Time Frame: Baseline and Week 26
The change from baseline is the Week 26 SBP minus the Week 0 SBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy.
Baseline and Week 26
Baseline Sitting Diastolic Blood Pressure (DBP)
Time Frame: Baseline
Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in DBP at Week 26 data are presented in the following outcome measure.
Baseline
Change From Baseline in DBP at Week 26
Time Frame: Baseline and Week 26
The change from baseline is the Week 26 DBP minus the Week 0 DBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy.
Baseline and Week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 9, 2013

Primary Completion (Actual)

July 28, 2016

Study Completion (Actual)

July 28, 2016

Study Registration Dates

First Submitted

October 7, 2013

First Submitted That Met QC Criteria

October 7, 2013

First Posted (Estimate)

October 9, 2013

Study Record Updates

Last Update Posted (Actual)

September 29, 2017

Last Update Submitted That Met QC Criteria

September 1, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8835-003
  • 2013-002519-90 (EudraCT Number)
  • B1521022 (Other Identifier: Pfizer Protocol Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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