Overview

This trial is active, not recruiting.

Condition type 2 diabetes mellitus
Treatments ertugliflozin 5 mg, ertugliflozin 10 mg, glimerpiride, placebo to ertugliflozin, placebo to glimepiride, metformin, sitagliptin
Phase phase 3
Sponsor Merck Sharp & Dohme Corp.
Collaborator Pfizer
Start date December 2013
End date April 2017
Trial size 1230 participants
Trial identifier NCT01999218, 2013-003582-34, 8835-002, B1521013

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 duration of the trial will be up to approximately 122 weeks. This will include a 1-week screening period, an up to 13-week wash-off/titration/dose stabilization period, a 2-week placebo run-in period, a 104-week double-blind, active comparator-controlled treatment period, and a post-treatment telephone contact 14 days after the last dose of study drug. 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.

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)
Participants randomized to ertugliflozin 5 mg once daily (q.d.) will take one ertugliflozin 5 mg tablet, one matching placebo tablet for ertugliflozin 10 mg, and matching placebo(s) for glimepiride daily from Day 1 to Week 104.
ertugliflozin 5 mg MK-8835
Ertugliflozin, 5 mg, oral, once daily, from Day 1 to Week 104
placebo to ertugliflozin
Matching placebo to ertugliflozin, 5 mg and/or 10 mg, oral, once daily, from Day 1 to Week 104
placebo to glimepiride
Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104.
metformin
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.
sitagliptin
Open label, oral, once daily, rescue medication as required.
(Experimental)
Participants randomized to ertugliflozin 15 mg q.d. will take one 5 mg tablet and one 10 mg tablet of ertugliflozin and matching placebo(s) for glimepiride daily from Day 1 to Week 104.
ertugliflozin 5 mg MK-8835
Ertugliflozin, 5 mg, oral, once daily, from Day 1 to Week 104
ertugliflozin 10 mg
Ertugliflozin, 10 mg, oral, once daily from Day 1 to Week 104.
placebo to glimepiride
Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104.
metformin
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.
sitagliptin
Open label, oral, once daily, rescue medication as required.
(Active Comparator)
Participants randomized to glimepiride will take glimepiride tablets (1 and/or 2 mg) to a maximum of 8 mg and matching placebo tablets for ertugliflozin 5 mg and 10 mg daily from Day 1 to Week 104.
glimerpiride
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
placebo to ertugliflozin
Matching placebo to ertugliflozin, 5 mg and/or 10 mg, oral, once daily, from Day 1 to Week 104
metformin
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.
sitagliptin
Open label, oral, once daily, rescue medication as required.

Primary Outcomes

Measure
Change from Baseline in Hemoglobin A1C at Week 52
time frame: Baseline and Week 52
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
Number of Participants with an Adverse Event of Symptomatic Hypoglycemia
time frame: Up to Week 52
Change from Baseline in Body Weight at Week 52
time frame: Baseline and Week 52
Change from Baseline in Systolic Blood Pressure at Week 52
time frame: Baseline and Week 52

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - 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. Exclusion Criteria: - 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 - Previous randomization in a study with ertugliflozin - Participation in other studies involving investigational drug(s) within 30 days of study participation and/or during the pre-randomization period - A surgical procedure within 6 weeks prior to study participation or planned major surgery during the trial - A positive urine pregnancy test - Pregnant or breast-feeding, or expecting to conceive during the trial, including 14 days following the last dose of study drug - Undergoing hormonal therapy in preparation to donate eggs during the period of the trial, including 14 days following the last dose of study drug - Consumption of more than 2 alcoholic drinks per day or engages in binge drinking - 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

Additional Information

Official title A Phase III, Multicenter, Randomized, Double-Blind, Active-Comparator-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Ertugliflozin (MK-8835/PF-04971729) Compared With the Addition of Glimepiride in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..