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) | RxWiki

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)

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: Ertugliflozin 5 mg Drug: Ertugliflozin 15 mg Drug: Placebo to Ertugliflozin Other: Glimepiride Drug: Placebo to Glimepiride Biological: Basal Insulin Drug: Metformin
Phase	Phase 3
Sponsor	Merck Sharp & Dohme Corp.
Responsible Party	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier	NCT02033889
First Received	January 9, 2014
Last Updated	April 24, 2014
Last verified	April 2014

Tracking Information[ + expand ][ + ]

First Received Date	January 9, 2014
Last Updated Date	April 24, 2014
Start Date	January 2014
Estimated Primary Completion Date	June 2017
Current Primary Outcome Measures	Change from Baseline in Hemoglobin A1c [Time Frame: Baseline and Week 26] [Designated as safety issue: No] Number of Participants Experiencing An Adverse Event (AE) [Time Frame: Up to Week 106] [Designated as safety issue: Yes] Number of Participants Discontinuing Study Treatment Due to an AE [Time Frame: Up to Week 104] [Designated as safety issue: Yes]
Current Secondary Outcome Measures	Change from Baseline in Fasting Plasma Glucose [Time Frame: Baseline and Week 26] [Designated as safety issue: No] Change from Baseline in Body Weight at Week 26 [Time Frame: Baseline and Week 26] [Designated as safety issue: No] Number of participants with a HbA1c of <7% (53 mmol/mol) at Week 26 [Time Frame: Week 26] [Designated as safety issue: No] Change from Baseline in Systolic Blood Pressure [Time Frame: Baseline and Week 26] [Designated as safety issue: No] Change from Baseline in Diastolic Blood Pressure [Time Frame: Baseline and Week 26] [Designated as safety issue: No] Change from Baseline in Bone Mineral Density at Week 26 [Time Frame: Baseline and Week 26] [Designated as safety issue: Yes] Change from Baseline in Bone Mineral Density at Week 52 [Time Frame: Baseline and Week 52] [Designated as safety issue: Yes] Change from Baseline in Bone Mineral Density at Week 104 [Time Frame: Baseline and Week 104] [Designated as safety issue: Yes] Number of participants with HbA1c <=6.5% (48 mmol/mol) at Week 26 [Time Frame: Week 26] [Designated as safety issue: No] Number of participants requiring glycemic rescue therapy up to Week 26 [Time Frame: Up to Week 26] [Designated as safety issue: No] Time to glycemic rescue therapy up to Week 26 [Time Frame: Up to Week 26] [Designated as safety issue: No] Change from baseline in bone biomarkers at Week 26 [Time Frame: Baseline and Week 26] [Designated as safety issue: Yes] Change from baseline in bone biomarkers at Week 52 [Time Frame: Baseline and Week 52] [Designated as safety issue: Yes] Change from baseline in bone biomarkers at Week 104 [Time Frame: Baseline and Week 104] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief Title	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)
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
Brief 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.
Detailed 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).
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: Ertugliflozin 5 mg Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Other Names: MK-8835Drug: Ertugliflozin 15 mg Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Other Names: MK-8835Drug: Placebo to Ertugliflozin Placebo to ertuglioflozin, orally once daily from Day 1 to Week 104. Other: Glimepiride 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. Other Names: Amaryl GLIMPID GLIMY Drug: 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. Biological: Basal Insulin 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. Other Names: Insulin glargine Insulin detemir NPH insulin Degludec Drug: Metformin Metformin >=1500 mg/day, orally, once a day Other Names: Glucophage XR Carbophage SR Riomet Fortamet Glumetza Obimet Gluformin Dianben Diabex Diaformin Siofor Metfogamma
Study Arm (s)	Experimental: Ertuglifozin 5 mg 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. Experimental: Ertugliflozin 15 mg 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. Placebo Comparator: Placebo to Ertugliflozin 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.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	600
Estimated Completion Date	June 2017
Estimated Primary Completion Date	December 2015
Eligibility Criteria	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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Toll Free Number 1-888-577-8839
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT02033889
Other Study ID Numbers	8835-007
Has Data Monitoring Committee	Yes
Information Provided By	Merck Sharp & Dohme Corp.
Study Sponsor	Merck Sharp & Dohme Corp.
Collaborators	Pfizer
Investigators	Study Director: Medical Director Merck Sharp & Dohme Corp.
Verification Date	April 2014

Locations[ + expand ][ + ]

Call for Information (Investigational Site 1126)	Riverside, California, United States, 92506 Recruiting
Call for Information (Investigational Site 1132)	Tustin, California, United States, 92780 Recruiting
Call for Information (Investigational Site 1134)	Hialeah, Florida, United States, 33012 Recruiting
Call for Information (Investigational Site 1112)	Savannah, Georgia, United States, 31419 Recruiting
Call for Information (Investigational Site 1125)	Savannah, Georgia, United States, 31406 Recruiting
Call for Information (Investigational Site 1107)	Greensboro, North Carolina, United States, 27408 Recruiting
Call for Information (Investigational Site 1131)	Fargo, North Dakota, United States, 58103 Recruiting
Call for Information (Investigational Site 1129)	Mount Pleasant, South Carolina, United States, 29464 Recruiting
Call for Information (Investigational Site 1117)	Spartanburg, South Carolina, United States, 29303 Recruiting
Call for Information (Investigational Site 1115)	Corpus Christi, Texas, United States, 78404 Recruiting
Call for Information (Investigational Site 1138)	Dallas, Texas, United States, 75230 Recruiting
Call for Information (Investigational Site 1193)	Houston, Texas, United States, 77801 Recruiting
Call for Information (Investigational Site 1121)	Houston, Texas, United States, 77024 Recruiting
Call for Information (Investigational Site 1111)	Schertz, Texas, United States, 78154 Recruiting
Call for Information (Investigational Site 1109)	Spring, Texas, United States, 77379 Recruiting
Call for Information (Investigational Site 1122)	Walla Walla, Washington, United States, 99362 Recruiting