A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo 5 mg; Drug: Ertugliflozin 5 mg; Drug: Ertugliflozin 10 mg; Drug: Placebo 10 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01986855

2013-003587-31 (EudraCT Number)

8835-001

B1521016 (Other Identifier)

Details and patient eligibility

About

This study will evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in participants with Type 2 diabetes mellitus with Stage 3 Chronic Kidney Disease (CKD) who have inadequate glycemic control on background antihyperglycemic therapy. The duration of this trial will be up to 67 weeks. This study will consist of a 1-week Screening Period, a 10-week wash-off period from metformin, if needed, and a 2-week placebo run-in period, a 52-week double-blind treatment period, and a 14-day post-treatment follow-up period. The primary objective of this trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared to the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.

Full description

Participants who meet protocol-defined glycemic rescue criteria will be permitted to have an adjustment in the dose(s) of background antihyperglycemic agent (AHA) therapy or addition of new AHA therapy as directed by their investigator until the participant no longer meets the rescue criteria.

Enrollment: 468 patients

Sex: All

Ages: 25+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of Type 2 diabetes mellitus in accordance with American Diabetes Association guidelines
• Have Stage 3 chronic kidney disease
• On stable diabetes therapy (diet/exercise therapy alone or anti-hyperglycemic agents [AHA] monotherapy or combination therapy) for at least 6 weeks prior to study participation OR on metformin (with or without diet/exercise therapy or other AHA therapy) and is willing to undergo a 10-week metformin wash-off period
• Have an estimated glomerular filtration rate (eGFR) of ≥30 to <60 mL/min/1.73m^2
• Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2
• Male, postmenopausal female or surgically sterile female
• If a female of reproductive potential, agrees 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 of type 1 diabetes mellitus or a history of ketoacidosis
• History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrine disorders, drug - or chemical-induced, and post-organ transplant)
• History of nephrotic range proteinuria with hypoalbuminemia and edema
• History of rapidly progressive glomerulonephritis, lupus nephritis, renal or systemic vasculitis, renal artery stenosis with renovascular hypertension, or ischemic nephropathy
• History of familial renal glucosuria
• History of renal dialysis or renal transplant or renal disease requiring treatment with any immunosuppressive agent
• A known hypersensitivity or intolerance to any (sodium-glucose co-transporter 2) SGLT2 inhibitor
• On a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable
• Has undergone bariatric surgery within the past 12 months
• Has been treated with rosiglitazone or other SGLT2 inhibitors within 12 weeks of study participation
• Has active, obstructive uropathy or indwelling urinary catheter
• 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 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)
• Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or any other clinically significant hematological disorder (such as 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 active symptomatic gallbladder disease
• Has any clinically significant malabsorption condition
• If taking thyroid replacement therapy, has not been on a stable dose for at least 6 weeks prior to study participation
• Has been previously randomized in a study with ertugliflozin
• Has participated in other studies involving an investigational drug within 30 days prior or during study participation
• Has undergone a surgical procedure within 6 weeks prior to or during study participation
• Has a positive urine pregnancy test
• Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of study medication
• Planning to undergo hormonal therapy in preparation to donate eggs during the trial, including 14 days following the last dose of study medication
• Excessive consumption of alcoholic beverages or binge drinking
• Has donated blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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468 participants in 3 patient groups, including a placebo group

Ertugliflozin (5 mg)

Experimental group

Description:

Ertugliflozin, 5 mg, oral, one 5 mg ertugliflozin tablet and one placebo tablet, once daily for 52 weeks

Treatment:

Drug: Ertugliflozin 5 mg

Drug: Placebo 10 mg

Ertugliflozin (15 mg)

Experimental group

Description:

Ertugliflozin, 15 mg, oral, one 5 mg and one 10 mg tablet, once daily for 52 weeks

Treatment:

Drug: Ertugliflozin 10 mg

Placebo

Placebo Comparator group

Description:

Matching placebo

Treatment:

Drug: Placebo 5 mg

Drug: Placebo 10 mg