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)

NCT01958671 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 8835-0032013-002519-90B1521022
• Study Type: interventional
• Target: 461
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  Up to 54 weeks (including 2 weeks following last dose)

• Percentage of Participants Discontinuing Study Treatment Due to an 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.

  Up to 52 weeks

Secondary Outcomes (9)

• Change From Baseline in FPG at Week 26

  Baseline and Week 26

• Change From Baseline in Body Weight at Week 26

  Baseline and Week 26

• Percentage of Participants With A1C <7% (<53 mmol/Mol) at Week 26

  Week 26

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

  Baseline

• Change From Baseline in 2-hr PPG at Week 26

  Baseline and Week 26

Study Arms (3)

Ertugliflozin 5 mg/Ertugliflozin 5 mg

EXPERIMENTAL

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.

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

Ertugliflozin 15 mg/Ertugliflozin 15 mg

EXPERIMENTAL

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.

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

Placebo/Metformin

OTHER

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.

Drug: Placebo to Ertugliflozin; Drug: Metformin; Drug: Glimepiride

Interventions

Ertugliflozin 5 mg DRUG

One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).

Also known as: MK-8835, PF-04971729

Ertugliflozin 15 mg/Ertugliflozin 15 mg; Ertugliflozin 5 mg/Ertugliflozin 5 mg

Ertugliflozin 10 mg DRUG

One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).

Also known as: MK-8835, PF-04971729

Ertugliflozin 15 mg/Ertugliflozin 15 mg

Placebo to Ertugliflozin DRUG

One placebo tablet matching the ertugliflozin 5 mg tablet and/or 1 placebo tablet matching the ertugliflozin 10 mg tablet per day taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).

Ertugliflozin 5 mg/Ertugliflozin 5 mg; Placebo/Metformin

Metformin DRUG

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.

Also known as: Glucophage XR, Carbophage SR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor and Metfogamma.

Ertugliflozin 15 mg/Ertugliflozin 15 mg; Ertugliflozin 5 mg/Ertugliflozin 5 mg; Placebo/Metformin

Placebo to Metformin DRUG

1 tablet in the morning and 1 tablet in the evening for 2 weeks, 2 tablets in the morning and 1 tablet in the evening for 2 weeks and 2 tablets in the morning and 2 tablets in the evening, thereafter.

Ertugliflozin 15 mg/Ertugliflozin 15 mg; Ertugliflozin 5 mg/Ertugliflozin 5 mg

Glimepiride DRUG

Dosing and titration of glimepiride as rescue therapy was determined by the investigator.

Ertugliflozin 15 mg/Ertugliflozin 15 mg; Ertugliflozin 5 mg/Ertugliflozin 5 mg; Placebo/Metformin

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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Related Publications (10)

• Terra SG, Focht K, Davies M, Frias J, Derosa G, Darekar A, Golm G, Johnson J, Saur D, Lauring B, Dagogo-Jack S. Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone. Diabetes Obes Metab. 2017 May;19(5):721-728. doi: 10.1111/dom.12888. Epub 2017 Feb 22.

  PMID: 28116776 RESULT

• Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.

  PMID: 34213819 DERIVED

• Gallo S, Raji A, Calle RA, Pong A, Meyer C. The effects of ertugliflozin on beta-cell function: Pooled analysis from four phase 3 randomized controlled studies. Diabetes Obes Metab. 2020 Dec;22(12):2267-2275. doi: 10.1111/dom.14149. Epub 2020 Aug 27.

  PMID: 32700393 DERIVED

• 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

• 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

• Liu J, Pong A, Gallo S, Darekar A, Terra SG. Effect of ertugliflozin on blood pressure in patients with type 2 diabetes mellitus: a post hoc pooled analysis of randomized controlled trials. Cardiovasc Diabetol. 2019 May 7;18(1):59. doi: 10.1186/s12933-019-0856-7.

  PMID: 31064361 DERIVED

• Aronson R, Frias J, Goldman A, Darekar A, Lauring B, Terra SG. Long-term efficacy and safety of ertugliflozin monotherapy in patients with inadequately controlled T2DM despite diet and exercise: VERTIS MONO extension study. Diabetes Obes Metab. 2018 Jun;20(6):1453-1460. doi: 10.1111/dom.13251. Epub 2018 Feb 23.

  PMID: 29419917 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin; Metformin; glimepiride

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

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: October 7, 2013
• First Posted: October 9, 2013
• Study Start: October 9, 2013
• Primary Completion: July 28, 2016
• Study Completion: July 28, 2016
• Last Updated: September 29, 2017
• Results First Posted: September 29, 2017

Record last verified: 2017-07