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 28, 2014
Last verified: August 2014

January 13, 2014
August 28, 2014
March 2014
October 2015   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT02036515 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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)
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: Ertugliflozin (5 mg)
    Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks
    Other Names:
    • MK-8835
    • PF-04971729
  • Drug: Ertugliflozin (15 mg)
    Ertugliflozin, oral, 5 mg and 10 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 (5 mg)
    Ertugliflozin, 5 mg, oral, once daily for 52 weeks
    Interventions:
    • Drug: Ertugliflozin (5 mg)
    • Drug: Placebo
    • Drug: Metformin
    • Drug: Sitagliptin
    • Drug: Glimepiride
    • Biological: Insulin
  • Experimental: Ertugliflozin (15 mg)
    Ertugliflozin, 15 mg, oral, once daily for 52 weeks
    Interventions:
    • Drug: Ertugliflozin (15 mg)
    • Drug: Metformin
    • Drug: Sitagliptin
    • Drug: Glimepiride
    • Biological: Insulin
  • Placebo Comparator: Placebo
    Matching placebo to ertuglifozin, oral, once daily for 52 weeks
    Interventions:
    • Drug: Placebo
    • Drug: Metformin
    • Drug: Sitagliptin
    • Drug: Glimepiride
    • Biological: Insulin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
405
April 2016
October 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Toll Free Toll Free Number 1-888-577-8839
United States,   Hungary
 
NCT02036515
8835-006, 2013-003697-26, B1521015
Yes
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Pfizer
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP