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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Glimepiride; Drug: Placebo to Ertugliflozin; Drug: Metformin; Drug: Placebo to Metformin; Drug: Ertugliflozin 5 mg; Drug: Ertugliflozin 10 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01958671

B1521022 (Other Identifier)

2013-002519-90 (EudraCT Number)

8835-003

Details and patient eligibility

About

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.

Enrollment: 461 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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461 participants in 3 patient groups

Ertugliflozin 5 mg/Ertugliflozin 5 mg

Experimental group

Description:

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.

Treatment:

Drug: Glimepiride

Drug: Placebo to Ertugliflozin

Drug: Ertugliflozin 5 mg

Drug: Metformin

Drug: Placebo to Metformin

Ertugliflozin 15 mg/Ertugliflozin 15 mg

Experimental group

Description:

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.

Treatment:

Drug: Glimepiride

Drug: Ertugliflozin 10 mg

Drug: Ertugliflozin 5 mg

Drug: Metformin

Drug: Placebo to Metformin

Placebo/Metformin

Other group

Description:

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.

Treatment:

Drug: Glimepiride

Drug: Placebo to Ertugliflozin

Drug: Metformin