A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007).

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo to Ertugliflozin; Other: Glimepiride; Drug: Ertugliflozin 15 mg; Drug: Placebo to Glimepiride; Drug: Metformin; Drug: Ertugliflozin 5 mg; Biological: Basal Insulin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02033889

MK-8835-007 (Other Identifier)

8835-007

2013-003290-95 (EudraCT Number)

B1521017 (Other Identifier)

Details and patient eligibility

About

This is an efficacy and safety study of ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin monotherapy. The primary study hypothesis is that at Week 26, the mean reduction from baseline in hemoglobin A1c (HbA1c) for ertugliflozin is greater than that for placebo.

Full description

The trial includes a 13-15 week run-in period prior to randomization, and a 26-week, double-blind, placebo-controlled treatment period followed by a 78-week double-blind, extension period.

Enrollment: 621 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of T2DM in accordance to American Diabetes Association guidelines
• Participants must be receiving metformin monotherapy for less than 8 weeks prior to study participation or require change in their diabetes regimen to remain eligible to participate in the trial (including discontinuing anti-hyperglycemic agent [AHA] therapy) and must have a hemoglobin A1c of 7.0 to 10.5% (53-91 mmol/mol) after at least 8 weeks on a regimen of metformin monotherapy

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 glimepiride
• 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 6 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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621 participants in 3 patient groups, including a placebo group

Ertuglifozin 5 mg

Experimental group

Description:

Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.

Treatment:

Drug: Placebo to Glimepiride

Biological: Basal Insulin

Drug: Metformin

Drug: Ertugliflozin 5 mg

Other: Glimepiride

Drug: Placebo to Ertugliflozin

Ertugliflozin 15 mg

Experimental group

Description:

Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.

Treatment:

Drug: Placebo to Glimepiride

Biological: Basal Insulin

Drug: Metformin

Other: Glimepiride

Drug: Ertugliflozin 15 mg

Placebo/Glimepiride

Placebo Comparator group

Description:

Placebo to ertugliflozin, orally once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received blinded glimepiride. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.

Treatment:

Biological: Basal Insulin

Drug: Metformin

Other: Glimepiride

Drug: Placebo to Ertugliflozin