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)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled, 26-week Multicenter Study With a 26-Week Extension to Evaluate the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01958671
• Other study ID #: 8835-003
• Secondary ID: 2013-002519-90B1
• Status: Completed
• Phase: Phase 3
• First received: October 7, 2013
• Last updated: September 1, 2017
• Start date: October 9, 2013
• Est. completion date: July 28, 2016

Study information

• Verified date: July 2017
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 461
• Est. completion date: July 28, 2016
• Est. primary completion date: July 28, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Ertugliflozin 5 mg
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
• Ertugliflozin 10 mg
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
• Placebo to Ertugliflozin
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).
• Metformin
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.
• Placebo to Metformin
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.
• Glimepiride
Dosing and titration of glimepiride as rescue therapy was determined by the investigator.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Pfizer

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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	Change From Baseline in FPG at Week 26	The change from baseline is the Week 26 FPG minus the Week 0 FPG. Laboratory measurements were performed after an overnight fast =10 hours in duration. Data presented exclude data following the initiation of glycemic rescue therapy.	Baseline and Week 26
Secondary	Change From Baseline in Body Weight at Week 26	The change from baseline is the Week 26 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy.	Baseline and Week 26
Secondary	Percentage of Participants With A1C <7% (<53 mmol/Mol) at Week 26	A1C is measured as percent. Laboratory measurements were performed after an overnight fast =10 hours in duration. Data presented exclude data following the initiation of rescue therapy.	Week 26
Secondary	Baseline 2-hour Post-prandial Glucose (2-hr PPG) Level	Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the Mixed Meal Tolerance Test (MMTT). Change from baseline in 2-hr PPG level at Week 26 data are presented in the following outcome measure.	Baseline
Secondary	Change From Baseline in 2-hr PPG at Week 26	The change from baseline is the Week 26 2-hr PPG minus the Week 0 2-hr PPG. Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the MMTT. Data presented exclude data following the initiation of rescue therapy.	Baseline and Week 26
Secondary	Baseline Sitting Systolic Blood Pressure (SBP)	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in SBP at Week 26 data are presented in the following outcome measure.	Baseline
Secondary	Change From Baseline in SBP at Week 26	The change from baseline is the Week 26 SBP minus the Week 0 SBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy.	Baseline and Week 26
Secondary	Baseline Sitting Diastolic Blood Pressure (DBP)	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in DBP at Week 26 data are presented in the following outcome measure.	Baseline
Secondary	Change From Baseline in DBP at Week 26	The change from baseline is the Week 26 DBP minus the Week 0 DBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy.	Baseline and Week 26