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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01986855
First received: November 12, 2013
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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 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 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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Ertugliflozin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) in Subjects With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Background Antihyperglycemic Therapy

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change from Baseline in A1C at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Overall cohort of Stage 3 CKD, estimated glomerular filtration rate (eGFR) of ≥30 to <60 mL/min/1.73m^2

  • Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to 54 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Discontinued Study Treatment due to an AE [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from Baseline in A1C at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Cohort of Stage 3A CKD, eGFR of ≥45 to <60 mL/min/1.73m^2

  • Change from Baseline in Body Weight at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Cohort of Stage 3A CKD, eGFR of ≥45 to <60 mL/min/1.73m^2

  • Change from Baseline in Systolic Blood Pressure at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Cohort of Stage 3A CKD, eGFR of ≥45 to <60 mL/min/1.73m^2

  • Change from Baseline in Fasting Plasma Glucose at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Cohort of Stage 3A CKD, eGFR of ≥45 to <60 mL/min/1.73m^2

  • Number of Participants with an A1C of <7% (53 mmol/mol) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    Cohort of Stage 3A CKD, eGFR of ≥45 to <60 mL/min/1.73m^2


Estimated Enrollment: 468
Study Start Date: December 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ertugliflozin (5 mg)
Ertugliflozin, 5 mg, oral, one 5 mg ertugliflozin tablet and one placebo tablet, once daily for 52 weeks
Drug: Ertugliflozin
Ertugliflozin, oral, 5 mg or 5 mg and 10 mg tablet once daily for 52 weeks
Other Names:
  • MK-8835
  • PF-04971729
Drug: Placebo
Placebo
Other Name: Placebo, oral, tablet, 10 mg or 5 mg and 10 mg tablet once daily for 52 weeks
Experimental: Ertugliflozin (15 mg)
Ertugliflozin, 15 mg, oral, one 5 mg and one 10 mg tablet, once daily for 52 weeks
Drug: Ertugliflozin
Ertugliflozin, oral, 5 mg or 5 mg and 10 mg tablet once daily for 52 weeks
Other Names:
  • MK-8835
  • PF-04971729
Placebo Comparator: Placebo
Matching placebo
Drug: Placebo
Placebo
Other Name: Placebo, oral, tablet, 10 mg or 5 mg and 10 mg tablet once daily for 52 weeks

  Eligibility

Ages Eligible for Study:   25 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of T2DM
  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01986855

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 36 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Pfizer
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01986855     History of Changes
Other Study ID Numbers: 8835-001, 2013-003587-31, B1521016
Study First Received: November 12, 2013
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypoglycemic Agents
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Renal Insufficiency
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014