Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01999218

B1521013 (Other Identifier)

2013-003582-34 (EudraCT Number)

8835-002

Details and patient eligibility

About

This study will evaluate the efficacy and safety of the addition of ertugliflozin (MK-8835/PF-04971729) compared with the addition of glimepiride in participants with T2DM who have inadequate glycemic control on metformin. The primary hypothesis of this study is that after 52 weeks, the change from baseline in hemoglobin A1c (A1C) in participants treated with the addition of ertugliflozin 15 mg once daily is non-inferior compared with that in participants treated with the addition of glimepiride.

Full description

The duration of the trial will be up to approximately 122 weeks. This will include a 1-week screening period, an up to 13-week wash-off/titration/dose stabilization period, a 2-week placebo run-in period, a 104-week double-blind, active comparator-controlled treatment period, and a post-treatment telephone contact 14 days after the last dose of study drug.

Enrollment: 1,326 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of T2DM in accordance to American Diabetes Association guidelines
• On metformin monotherapy or metformin in combination with a single allowable anti-hyperglycemic agent (AHA), DPP-4 inhibitors, meglitinides and AGIs are listed as allowable AHAs along with sulfonylureas prior to study participation.
• Body Mass Index (BMI) ≥18.0 kg/m^2
• Male or female not of reproductive potential
• If a female of reproductive potential, agree to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug.

Exclusion criteria

• History or presence of type 1 diabetes mellitus or a history of ketoacidosis
• History of other specific types of diabetes (eg, genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant).
• A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor
• Use of the following prohibited therapeutic agents within 12 weeks of study participation: insulin, injectable anti-hyperglycemic agents, pioglitazone or rosiglitazone, another SGLT2 inhibitor, bromocriptine (Cycloset®), colesevelam (Welchol®), and any other non-approved anti-hyperglycemic therapy
• Known hypersensitivity or intolerance to metformin or glimepiride
• On a weight-loss program or medication or medication associated with weight changes and is not weight-stable (>=5% change in body weight in the last 6 months)
• History of bariatric surgery less than 12 months prior to study participation
• 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
• Active, obstructive uropathy or an indwelling urinary catheter
• 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
• Known history of Human Immunodeficiency Virus (HIV)
• Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells
• A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C (assessed by medical history), primary biliary cirrhosis, or symptomatic gallbladder disease
• Any clinically significant malabsorption condition
• Being treated for hyperthyroidism, or on thyroid replacement therapy that has not been at a stable dose for at least 6 weeks prior to study participation
• Previous randomization in a study with ertugliflozin
• Participation in other studies involving investigational drug(s) within 30 days of study participation and/or during the pre-randomization period
• A surgical procedure within 6 weeks prior to study participation or planned major surgery during the trial
• A positive urine pregnancy test
• Pregnant or breast-feeding, or expecting to conceive during the trial, including 14 days following the last dose of study drug
• Undergoing hormonal therapy in preparation to donate eggs during the period of the trial, including 14 days following the last dose of study drug
• Consumption of more than 2 alcoholic drinks per day or engages in binge drinking
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,326 participants in 3 patient groups

Ertugliflozin 5 mg

Experimental group

Description:

Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104

Treatment:

Drug: Metformin

Drug: Placebo to Glimepiride

Drug: Placebo to Ertugliflozin

Drug: Ertugliflozin 5 mg

Drug: Sitagliptin

Ertugliflozin 15 mg

Experimental group

Description:

Ertugliflozin 15 mg QD from Day 1 to Week 104

Treatment:

Drug: Metformin

Drug: Ertugliflozin 10 mg

Drug: Placebo to Glimepiride

Drug: Ertugliflozin 5 mg

Drug: Sitagliptin

Glimepiride up to 8 mg

Active Comparator group

Description:

Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104

Treatment:

Drug: Glimerpiride

Drug: Metformin

Drug: Placebo to Ertugliflozin

Drug: Sitagliptin