Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02036515
First received: January 13, 2014
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

This is a safety and efficacy study of ertugliflozin (MK-8835/PF-04971729) in the treatment of participants with type 2 diabetes mellitus who have inadequate glycemic control on metformin and sitagliptin. The primary objective of the 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 with 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 (5 mg)
Drug: Ertugliflozin (15 mg)
Drug: Placebo
Drug: Metformin
Drug: Sitagliptin
Drug: Glimepiride
Biological: Insulin
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, Parallel-Group Clinical Trial to Evaluate the Safety and Efficacy of Ertugliflozin (MK-8835/PF-04971729) in the Treatment of Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change from baseline in hemoglobin A1C at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Number of Participants Experiencing An Adverse Event (AE) [ Time Frame: Up to Week 54 ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to Week 52 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in fasting plasma glucose (FPG) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Change from baseline in body weight at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Number of participants with an A1C <7% (53 mmol/mol) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
  • Change from baseline in systolic blood pressure at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]

Estimated Enrollment: 405
Study Start Date: March 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ertugliflozin (5 mg)
Ertugliflozin, 5 mg, oral, once daily for 52 weeks
Drug: Ertugliflozin (5 mg)
Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks
Other Names:
  • MK-8835
  • PF-04971729
Drug: Placebo
Matching placebo for ertugliflozin 5 mg, oral, and matching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks
Drug: 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.
Other Names:
  • Glucophage
  • Glucophage XR
Drug: Sitagliptin
Participants are to remain on their stable doses of sitagliptin (oral, 100 mg once daily) while receiving blinded investigational product during the double-blind treatment period.
Other Name: JANUVIA®
Drug: Glimepiride
Glimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion
Other Name: AMARYL
Biological: Insulin
Insulin glargine rescue medication, injectable, as required. In the event that an investigator considers use of glimepiride to not be appropriate for a participant meeting protocol specified glycemic rescue criteria, insulin glargine can be initiated as the rescue medication, and managed by the investigator according to clinical practice guidelines of the local country.
Experimental: Ertugliflozin (15 mg)
Ertugliflozin, 15 mg, oral, once daily for 52 weeks
Drug: Ertugliflozin (15 mg)
Ertugliflozin, oral, 5 mg and 10 mg tablet once daily for 52 weeks
Other Names:
  • MK-8835
  • PF-04971729
Drug: 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.
Other Names:
  • Glucophage
  • Glucophage XR
Drug: Sitagliptin
Participants are to remain on their stable doses of sitagliptin (oral, 100 mg once daily) while receiving blinded investigational product during the double-blind treatment period.
Other Name: JANUVIA®
Drug: Glimepiride
Glimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion
Other Name: AMARYL
Biological: Insulin
Insulin glargine rescue medication, injectable, as required. In the event that an investigator considers use of glimepiride to not be appropriate for a participant meeting protocol specified glycemic rescue criteria, insulin glargine can be initiated as the rescue medication, and managed by the investigator according to clinical practice guidelines of the local country.
Placebo Comparator: Placebo
Matching placebo to ertuglifozin, oral, once daily for 52 weeks
Drug: Placebo
Matching placebo for ertugliflozin 5 mg, oral, and matching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks
Drug: 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.
Other Names:
  • Glucophage
  • Glucophage XR
Drug: Sitagliptin
Participants are to remain on their stable doses of sitagliptin (oral, 100 mg once daily) while receiving blinded investigational product during the double-blind treatment period.
Other Name: JANUVIA®
Drug: Glimepiride
Glimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion
Other Name: AMARYL
Biological: Insulin
Insulin glargine rescue medication, injectable, as required. In the event that an investigator considers use of glimepiride to not be appropriate for a participant meeting protocol specified glycemic rescue criteria, insulin glargine can be initiated as the rescue medication, and managed by the investigator according to clinical practice guidelines of the local country.

Detailed Description:

The duration of the trial will be approximately 69 weeks. This will include a 1-week Screening Period, an up to 12-week wash-off/titration /dose-stabilization period, a 2-week single-blind, placebo run-in period, a 52-week double-blind, placebo-controlled treatment period (including a 26-week Phase A and 26-week Phase B), and a post-treatment telephone contact 14 days after the last dose of blinded investigational product.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of type 2 diabetes mellitus (T2DM)
  • On stable diabetes therapy of metformin with either sitagliptin or another dipeptidyl peptidase-4 (DPP-4) inhibitor or a sulfonylurea (SU) prior to study participation and is willing to wash-off/switch from another DPP-4 inhibitor/SU to sitagliptin
  • 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)
  • A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) or DPP-4 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 or >12 months and is not weight stable
  • Has been treated with insulin (except for short-term use [<= 7 days]), injectable antihyperglycemic agents (AHAs) (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other sodium-glucose co-transporter 2 (SGLT2) inhibitors, alpha glucosidase inhibitors or meglitinides, bromocriptine (Cycloset™), colesevelam (Welchol™), or any other nonapproved AHAs 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 nonalcoholic 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 planned major surgery 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: NCT02036515

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

  Show 26 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Pfizer
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02036515     History of Changes
Other Study ID Numbers: 8835-006, 2013-003697-26, B1521015
Study First Received: January 13, 2014
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Sitagliptin
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014