Overview

This trial is active, not recruiting.

Condition type 2 diabetes mellitus
Treatments ertugliflozin 5 mg, ertugliflozin 15 mg, placebo to ertugliflozin, glimepiride, placebo to glimepiride, basal insulin, metformin
Phase phase 3
Sponsor Merck Sharp & Dohme Corp.
Collaborator Pfizer
Start date December 2013
End date August 2017
Trial size 600 participants
Trial identifier NCT02033889, 2013-003290-95, 8835-007, B1521017

Summary

This is an efficacy and safety study of ertugliflozin in participants with type 2 diabetes mellitus 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Participants will receive 1 ertugliflozin 5 mg tablet and 1 placebo ertugliflozin 10 mg tablet per day. Participants requiring glycemic rescue during the 26-week initial treatment period (Phase A) will receive open-label glimepiride. This rescue will continue through the 78-week, double-blind, extension period (Phase B). If not rescued during Phase A, participants will receive placebo to glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) during Phase B. All participants will also receive metformin at a dose >=1500 mg/day in Phase A and B.
ertugliflozin 5 mg MK-8835
Ertugliflozin 5 mg orally (1 ertugliflozin 5 mg tablet and 1 placebo ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.
placebo to ertugliflozin
Placebo to ertuglioflozin (1 placebo ertugliflozin 5 mg tablet and/or 1 placebo ertugliflozin 10 mg tablet), orally once daily from Day 1 to Week 104.
glimepiride Amaryl
Glimepiride will be used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) in the 26-week initial period. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of blinded glimepiride is at the discretion of the investigator.
placebo to glimepiride
Placebo to glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of placebo to glimepiride is at the discretion of the investigator.
basal insulin Insulin glargine
Basal insulin will be used for participants requiring rescue therapy in Phase B. Dosing and titration of basal insulin is at the discretion of the Investigator.
metformin Glucophage XR
Metformin >=1500 mg/day, orally, once a day
(Experimental)
Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Participants will receive 1 ertugliflozin 5 mg tablet and 1 ertugliflozin 10 mg tablet per day. Participants requiring glycemic rescue during the 26-week initial treatment period (Phase A) will receive open-label glimepiride. This rescue will continue through the 78-week, double-blind, extension period (Phase B). If not rescued during Phase A, participants will receive placebo to glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) during Phase B. All participants will also receive metformin at a dose >=1500 mg/day in Phase A and B.
ertugliflozin 15 mg MK-8835
Ertugliflozin 15 mg orally (1 ertugliflozin 5 mg tablet and 1 ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.
glimepiride Amaryl
Glimepiride will be used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) in the 26-week initial period. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of blinded glimepiride is at the discretion of the investigator.
placebo to glimepiride
Placebo to glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of placebo to glimepiride is at the discretion of the investigator.
basal insulin Insulin glargine
Basal insulin will be used for participants requiring rescue therapy in Phase B. Dosing and titration of basal insulin is at the discretion of the Investigator.
metformin Glucophage XR
Metformin >=1500 mg/day, orally, once a day
(Placebo Comparator)
Placebo to ertuglioflozin, orally once daily from Day 1 to Week 104. Participants will receive 1 placebo ertugliflozin 5 mg tablet and 1 placebo ertugliflozin 10 mg tablet per day. Participants requiring glycemic rescue during the 26-week initial treatment period (Phase A) will receive open-label glimepiride. This rescue will continue through the 78-week, double-blind, extension period (Phase B). If not rescued during Phase A, participants will receive blinded glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) during Phase B. All participants will also receive metformin at a dose >=1500 mg/day in Phase A and B.
placebo to ertugliflozin
Placebo to ertuglioflozin (1 placebo ertugliflozin 5 mg tablet and/or 1 placebo ertugliflozin 10 mg tablet), orally once daily from Day 1 to Week 104.
glimepiride Amaryl
Glimepiride will be used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) in the 26-week initial period. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of blinded glimepiride is at the discretion of the investigator.
basal insulin Insulin glargine
Basal insulin will be used for participants requiring rescue therapy in Phase B. Dosing and titration of basal insulin is at the discretion of the Investigator.
metformin Glucophage XR
Metformin >=1500 mg/day, orally, once a day

Primary Outcomes

Measure
Change from Baseline in Hemoglobin A1c
time frame: Baseline and Week 26
Number of Participants Experiencing An Adverse Event (AE)
time frame: Up to Week 106
Number of Participants Discontinuing Study Treatment Due to an AE
time frame: Up to Week 104

Secondary Outcomes

Measure
Change from Baseline in Fasting Plasma Glucose
time frame: Baseline and Week 26
Change from Baseline in Body Weight at Week 26
time frame: Baseline and Week 26
Number of participants with a HbA1c of <7% (53 mmol/mol) at Week 26
time frame: Week 26
Change from Baseline in Systolic Blood Pressure
time frame: Baseline and Week 26
Change from Baseline in Diastolic Blood Pressure
time frame: Baseline and Week 26
Change from Baseline in Bone Mineral Density at Week 26
time frame: Baseline and Week 26
Change from Baseline in Bone Mineral Density at Week 52
time frame: Baseline and Week 52
Change from Baseline in Bone Mineral Density at Week 104
time frame: Baseline and Week 104
Number of participants with HbA1c <=6.5% (48 mmol/mol) at Week 26
time frame: Week 26
Number of participants requiring glycemic rescue therapy up to Week 26
time frame: Up to Week 26
Time to glycemic rescue therapy up to Week 26
time frame: Up to Week 26
Change from baseline in bone biomarkers at Week 26
time frame: Baseline and Week 26
Change from baseline in bone biomarkers at Week 52
time frame: Baseline and Week 52
Change from baseline in bone biomarkers at Week 104
time frame: Baseline and Week 104

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 26-Week Multicenter Study With a 78-Week Extension To Evaluate The Efficacy And Safety Of Ertugliflozin In Subjects With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy.
Description The trial includes a 13-15 week run-in period prior to randomization, and a 26-week, double-blind, placebo-controlled treatment period (Phase A) followed by a 78-week double-blind, extension period (Phase B).
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..