A Study to Evaluate the Efficacy and Safety of Ertugliflozin in Asian Participants With Type 2 Diabetes and Inadequate Glycemic Control on Metformin Monotherapy (MK-8835-012)
NCT ID: NCT02630706
Last Updated: 2018-12-07
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
506 participants
INTERVENTIONAL
2015-12-16
2017-12-27
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Ertugliflozin 5 mg
Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin 5 mg
Ertugliflozin 5 mg oral tablet taken once daily
Placebo matching ertugliflozin
Placebo matching ertugliflozin (5-mg and/or 10-mg tablet) oral taken once daily
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.
Glimepiride
Glycemic rescue therapy with open-label glimepiride will be initiated in participants with glucose values exceeding protocol-specified values. Dosing and titration of open-label glimepiride rescue therapy will be at the Investigator's discretion.
Ertugliflozin 15 mg
Ertugliflozin 15 mg (ertugliflozin 5 mg + ertugliflozin 10 mg) administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Ertugliflozin 15 mg
Ertugliflozin 15 mg (5-mg and 10-mg tablets) oral taken once daily
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.
Glimepiride
Glycemic rescue therapy with open-label glimepiride will be initiated in participants with glucose values exceeding protocol-specified values. Dosing and titration of open-label glimepiride rescue therapy will be at the Investigator's discretion.
Placebo
Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (\>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
Placebo matching ertugliflozin
Placebo matching ertugliflozin (5-mg and/or 10-mg tablet) oral taken once daily
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.
Glimepiride
Glycemic rescue therapy with open-label glimepiride will be initiated in participants with glucose values exceeding protocol-specified values. Dosing and titration of open-label glimepiride rescue therapy will be at the Investigator's discretion.
Interventions
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Ertugliflozin 5 mg
Ertugliflozin 5 mg oral tablet taken once daily
Ertugliflozin 15 mg
Ertugliflozin 15 mg (5-mg and 10-mg tablets) oral taken once daily
Placebo matching ertugliflozin
Placebo matching ertugliflozin (5-mg and/or 10-mg tablet) oral taken once daily
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.
Glimepiride
Glycemic rescue therapy with open-label glimepiride will be initiated in participants with glucose values exceeding protocol-specified values. Dosing and titration of open-label glimepiride rescue therapy will be at the Investigator's discretion.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Type 2 diabetes mellitus as per American Diabetes Association guidelines.
* Metformin monotherapy (≥1500 mg/day) with an initial Screening A1C of 7.0-10.5% (53-91 mmol/mol) OR metformin monotherapy (\<1500 mg/day) with an initial Screening A1C of 7.5-11.0% (58-97 mmol/mol) OR dual combination therapy with metformin + sulfonylurea, dipeptidyl peptidase-4 (DDP-4) inhibitor, meglitinide, or alpha-glucosidase inhibitor with an initial Screening A1C of 6.5-9.5% (48-80 mmol/mol).
* Body mass index (BMI) ≥18.0 kg/m\^2.
* Male or female not of reproductive potential.
* Female of reproductive potential who agrees to remain abstinent from heterosexual activity or to use 2 acceptable combinations of contraception.
Exclusion Criteria
* History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant.)
* 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 start.
* Mean value for triplicate screening sitting systolic blood pressure \>160 mm Hg and/or diastolic blood pressure \>90 mm Hg after at least a 5-minute seated rest at screening
* Active, obstructive uropathy or indwelling urinary catheter.
* History of malignancy ≤5 years prior to study start, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
* Routinely consumes \>2 alcoholic drinks per day or \>14 alcoholic drinks per week or engages in binge drinking.
* Any clinically significant malabsorption condition.
* Is on a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable prior to study start.
* Has undergone bariatric surgery within the past 12 months or \>12 months and is not weight stable prior to study start.
* A known hypersensitivity or intolerance to any sodium glucose co-transporter (SGLT2) inhibitor.
* On a previous clinical study with ertugliflozin.
* Is taking blood pressure or lipid altering medications that have not been on a stable dose for at least 4 weeks prior to study start.
* Current treatment for hyperthyroidism.
* Male participants with a serum creatinine \>=1.3 mg/dL (\>=115 mol/L) or female participants with a serum creatinine \>=1.2 mg/dL (\>=106 mol/L) or participants with an estimated glomerular filtration rate (eGFR) \<55 mL/min/1.73m\^2 according to the 4-variable Modification of Diet in Renal Disease (MDRD) equation at screening.
* An aspartate transaminase (AST) or alanine transaminase (ALT) \>2X the upper limit of normal (ULN) range at screening, or a total bilirubin \>1.5 X the ULN unless the participant has a history of Gilbert's.
* On thyroid replacement therapy and has not been on a stable dose for at least 6 weeks prior to study start.
* A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease.
* Has been treated with any of the following agents within 12 weeks of study start or during the pre-randomization period: Insulin of any type (except for short-term use during concomitant illness or other stress), other injectable anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), another SGLT2 inhibitor, bromocriptine, colesevelam, rosiglitazone or pioglitazone, or any other AHA with the exception of the protocol-approved agents.
* Is on or likely to require treatment ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids.
* Has undergone a surgical procedure within 6 weeks prior to study start or has planned major surgery during the study.
* Pregnant or breast-feeding, or planning to conceive during the trial, including 14 days following the last dose of study medication.
* Planning to undergo hormonal therapy in preparation for egg donation during the trial, including 14 days following the last dose of study medication.
* Donated blood or blood products within 6 weeks of study start.
* Has Human Immunodeficiency Virus (HIV).
* Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells.
* Has clinically important hematological disorders (such as aplastic anemia, myeloproliferative or myelodyplastic syndromes, thrombocytopenia.)
18 Years
ALL
No
Sponsors
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Pfizer
INDUSTRY
Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Countries
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References
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Ji L, Liu J, Xu ZJ, Wei Z, Zhang R, Malkani S, Cater NB, Frederich R. Efficacy and Safety of Ertugliflozin Added to Metformin: A Pooled Population from Asia with Type 2 Diabetes and Overweight or Obesity. Diabetes Ther. 2023 Feb;14(2):319-334. doi: 10.1007/s13300-022-01345-6. Epub 2023 Feb 3.
Xu H, O'Gorman MT, Nepal S, James LP, Ginman K, Pithavala YK. Phase 1 Study Evaluating the Effects of the Proton Pump Inhibitor Rabeprazole and Food on the Pharmacokinetics of Lorlatinib in Healthy Participants. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1395-1404. doi: 10.1002/cpdd.1000. Epub 2021 Jul 20.
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.
Ji L, Liu Y, Miao H, Xie Y, Yang M, Wang W, Mu Y, Yan P, Pan S, Lauring B, Liu S, Huyck S, Qiu Y, Terra SG. Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia. Diabetes Obes Metab. 2019 Jun;21(6):1474-1482. doi: 10.1111/dom.13681. Epub 2019 Apr 5.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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B1521045
Identifier Type: OTHER
Identifier Source: secondary_id
MK-8835-012
Identifier Type: OTHER
Identifier Source: secondary_id
8835-012
Identifier Type: -
Identifier Source: org_study_id