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)

Phase 3CompletedNCT01958671

Merck Sharp & Dohme LLC461 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

461

Conditions

Type 2 Diabetes Mellitus

Interventions

MetforminDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change From Baseline In A1C at 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.

Time frame: Baseline and Week 26

Percentage of Participants Experiencing An Adverse Event (AE)

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.

Time frame: 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

Secondary Outcomes

Change From Baseline in FPG at 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.

Time frame: Baseline and Week 26

Change From Baseline in Body Weight at 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.

Time frame: Baseline and Week 26

Percentage of Participants With A1C <7% (<53 mmol/Mol) at 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.

Time frame: Week 26

Baseline 2-hour Post-prandial Glucose (2-hr PPG) Level

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.

Time frame: Baseline

Change From Baseline in 2-hr PPG at 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.

Time frame: Baseline and Week 26

Baseline Sitting Systolic Blood Pressure (SBP)

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.

Time frame: Baseline

Change From Baseline in SBP at 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.

Time frame: Baseline and Week 26

Baseline Sitting Diastolic Blood Pressure (DBP)

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.

Time frame: Baseline

Change From Baseline in DBP at 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.

Time frame: Baseline and Week 26