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

NCT01999218 | Completed Phase 3 Results DMC

• 3 other identifiers: 8835-0022013-003582-34B1521013
• Study Type: interventional
• Target: 1,326
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Hemoglobin A1C (A1C) at Week 52: Excluding Rescue Approach

  A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 52 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication. The primary study objective was the MK-8835 15 mg vs. glimepiride comparison; the MK-8835 5mg vs glimerpiride comparison was a secondary study objective.

  Baseline and Week 52

• Percentage of Participants Experiencing An Adverse Event (AE) Up to Week 106

  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

  Up to Week 106

• Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 104

  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

  Up to Week 104

Secondary Outcomes (3)

• Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 52: Excluding Rescue Approach

  Up to Week 52

• Change From Baseline in Body Weight at Week 52 Excluding Rescue Approach

  Baseline and Week 52

• Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 52 Excluding Rescue Approach

  Baseline and Week 52

Study Arms (3)

Ertugliflozin 5 mg

EXPERIMENTAL

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

Drug: Ertugliflozin 5 mg; Drug: Placebo to Ertugliflozin; Drug: Placebo to Glimepiride; Drug: Metformin; Drug: Sitagliptin

Ertugliflozin 15 mg

EXPERIMENTAL

Ertugliflozin 15 mg QD from Day 1 to Week 104

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

Glimepiride up to 8 mg

ACTIVE COMPARATOR

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

Drug: Glimerpiride; Drug: Placebo to Ertugliflozin; Drug: Metformin; Drug: Sitagliptin

Interventions

Ertugliflozin 5 mg DRUG

Ertugliflozin, 5 mg, oral, once daily, from Day 1 to Week 104

Also known as: MK-8835

Ertugliflozin 15 mg; Ertugliflozin 5 mg

Ertugliflozin 10 mg DRUG

Ertugliflozin, 10 mg, oral, once daily from Day 1 to Week 104.

Also known as: MK-8355

Ertugliflozin 15 mg

Glimerpiride DRUG

Glimepiride, oral tablets, initiated at 1 mg daily and titrated up to the maximum approved dose (8 mg daily based on the local country label) or maximum tolerated dose

Glimepiride up to 8 mg

Placebo to Ertugliflozin DRUG

Matching placebo to ertugliflozin, 5 mg and/or 10 mg, oral, once daily, from Day 1 to Week 104

Ertugliflozin 5 mg; Glimepiride up to 8 mg

Placebo to Glimepiride DRUG

Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104.

Ertugliflozin 15 mg; Ertugliflozin 5 mg

Metformin DRUG

Participants are to remain on their stable doses of metformin (oral, \>=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period. Participants on metformin \<1500 at screening are up-titrated to \>= 1500 daily.

Ertugliflozin 15 mg; Ertugliflozin 5 mg; Glimepiride up to 8 mg

Sitagliptin DRUG

Open label, oral, once daily, rescue medication as required.

Ertugliflozin 15 mg; Ertugliflozin 5 mg; Glimepiride up to 8 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Pfizer: collaborator

Related Publications (8)

• Hollander P, Hill J, Johnson J, Wei Jiang Z, Golm G, Huyck S, Terra SG, Mancuso JP, Engel SS, Lauring B, Liu J. Results of VERTIS SU extension study: safety and efficacy of ertugliflozin treatment over 104 weeks compared to glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin. Curr Med Res Opin. 2019 Aug;35(8):1335-1343. doi: 10.1080/03007995.2019.1583450. Epub 2019 Mar 25.

  PMID: 30760125 RESULT

• Gallo S, Calle RA, Terra SG, Pong A, Tarasenko L, Raji A. Effects of Ertugliflozin on Liver Enzymes in Patients with Type 2 Diabetes: A Post-Hoc Pooled Analysis of Phase 3 Trials. Diabetes Ther. 2020 Aug;11(8):1849-1860. doi: 10.1007/s13300-020-00867-1. Epub 2020 Jul 9.

  PMID: 32648108 DERIVED

• Patel S, Hickman A, Frederich R, Johnson S, Huyck S, Mancuso JP, Gantz I, Terra SG. Safety of Ertugliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Seven Phase 3 Randomized Controlled Trials. Diabetes Ther. 2020 Jun;11(6):1347-1367. doi: 10.1007/s13300-020-00803-3. Epub 2020 May 5.

  PMID: 32372382 DERIVED

• Liu J, Tarasenko L, Pong A, Huyck S, Wu L, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Aug;36(8):1277-1284. doi: 10.1080/03007995.2020.1760228. Epub 2020 May 13.

  PMID: 32324082 DERIVED

• Liu J, Tarasenko L, Pong A, Huyck S, Patel S, Hickman A, Mancuso JP, Ellison MC, Gantz I, Terra SG. Efficacy and safety of ertugliflozin in Hispanic/Latino patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Jul;36(7):1097-1106. doi: 10.1080/03007995.2020.1760227. Epub 2020 May 13.

  PMID: 32324065 DERIVED

• Cherney DZI, Heerspink HJL, Frederich R, Maldonado M, Liu J, Pong A, Xu ZJ, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Effects of ertugliflozin on renal function over 104 weeks of treatment: a post hoc analysis of two randomised controlled trials. Diabetologia. 2020 Jun;63(6):1128-1140. doi: 10.1007/s00125-020-05133-4. Epub 2020 Mar 31.

  PMID: 32236732 DERIVED

• Liu J, Patel S, Cater NB, Wu L, Huyck S, Terra SG, Hickman A, Darekar A, Pong A, Gantz I. Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2020 Apr;22(4):574-582. doi: 10.1111/dom.13931. Epub 2020 Jan 3.

  PMID: 31797522 DERIVED

• Hollander P, Liu J, Hill J, Johnson J, Jiang ZW, Golm G, Huyck S, Terra SG, Mancuso JP, Engel SS, Lauring B. Ertugliflozin Compared with Glimepiride in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin: The VERTIS SU Randomized Study. Diabetes Ther. 2018 Feb;9(1):193-207. doi: 10.1007/s13300-017-0354-4. Epub 2017 Dec 27.

  PMID: 29282633 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin; Metformin; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 3, 2013
• Study Start: December 16, 2013
• Primary Completion: April 18, 2017
• Study Completion: April 18, 2017
• Last Updated: April 2, 2019
• Results First Posted: May 11, 2018

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share