Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Glimepiride; Drug: Placebo to Sitagliptin; Drug: Sitagliptin; Drug: Placebo to Ertugliflozin; Drug: Ertugliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02226003

2014-001049-25 (EudraCT Number)

B1521047 (Other Identifier)

8835-017

Details and patient eligibility

About

This is a study to evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in combination with sitagliptin in the treatment of participants with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control on diet and exercise. The primary hypothesis of the study is that ertugliflozin plus sitagliptin is more effective in lowering of hemoglobin A1C (HbA1C) than placebo.

Full description

Each participant will be in the study for approximately 39 weeks including: a 1-week screening period, an 8-week (or greater) antihyperglycemic agent (AHA) wash-off period, a 2-week single-blind placebo run-in period, a 26-week double-blind treatment period, and a post-treatment telephone contact 14 days after the last dose of study drug.

Enrollment: 291 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 2 diabetes mellitus as per American Diabetes Association guidelines
• Not on antihyperglycemic agent (AHA) >=8 weeks with a Visit 1/Screening HbA1C >=8.0% and <=10.5% (>=64 mmol/mol and <=91 mmol/mol) OR on single allowable AHA (allowable AHAs prior to screening are: metformin, α-glucosidase inhibitors, sulfonylureas and glinides) with a Visit 1/Screening HbA1C >=7.5% and <=10.0% (>=58 mmol/mol and <=86 mmol/mol) OR on low-dose dual combination therapy (≤50% of maximum labeled dose of an AHA) with allowable AHAs with a Visit 1/Screening HbA1C >=7.5% and <=10.0% (>=58 mmol/mol and <=86 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 (or have their partner agree to) remain abstinent from heterosexual activity or to use 2 acceptable combinations of contraception.

Exclusion criteria

• History of type 1 diabetes mellitus or diabetic ketoacidosis
• 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
• A known hypersensitivity or intolerance to any sodium glucose co-transporter (SGLT2) inhibitor or sitagliptin
• 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 [i.e., <=7 days] during concomitant illness or other stress), other injectable anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other sodium glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4 inhibitors), bromocriptine (Cycloset™), colesevelam (Welchol™), any other AHA with the exception of the protocol-approved agents
• 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 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
• 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
• A known history of human immunodeficiency virus (HIV)
• A blood dyscrasia or any disorder causing hemolysis or unstable red blood cells, or a clinically important hematological disorder (e.g. aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
• 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
• Any clinically significant malabsorption condition
• Current treatment for hyperthyroidism
• On thyroid replacement therapy and not on a stable dose for at least 6 weeks prior study start
• On a previous clinical study with ertugliflozin
• Participated in other studies involving investigational drug(s) 30 days prior to study start
• Surgical procedure within 6 weeks prior to study start or major surgery planned during the trial
• Positive urine pregnancy test
• 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
• Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or engages in binge drinking
• Donated blood or blood products within 6 weeks of study start.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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291 participants in 3 patient groups, including a placebo group

Ertugliflozin 5 mg and Sitagliptin 100 mg

Experimental group

Description:

Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.

Treatment:

Drug: Glimepiride

Drug: Ertugliflozin

Drug: Placebo to Ertugliflozin

Drug: Sitagliptin

Ertugliflozin 15 mg and Sitagliptin 100 mg

Experimental group

Description:

Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.

Treatment:

Drug: Glimepiride

Drug: Ertugliflozin

Drug: Sitagliptin

Placebo to Ertugliflozin and Placebo to Sitagliptin

Placebo Comparator group

Description:

Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.

Treatment:

Drug: Glimepiride

Drug: Placebo to Sitagliptin

Drug: Placebo to Ertugliflozin