MK-8835/PF-04971729 vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01999218
First received: November 25, 2013
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

This study will evaluate the efficacy and safety of the addition of ertugliflozin (MK-8835/PF-04971729) compared with the addition of glimepiride in participants with T2DM who have inadequate glycemic control on metformin. The duration of the trial will be up to approximately 122 weeks. This will include a 1-week screening period, an up to 13-week wash-off/titration/dose stabilization period, a 2-week placebo run-in period, a 104-week double-blind, active comparator-controlled treatment period, and a post-treatment telephone contact 14 days after the last dose of study drug. The primary hypothesis of this study is that after 52 weeks, the change from baseline in hemoglobin A1C in participants treated with the addition of ertugliflozin 15 mg once daily is non-inferior compared with that in participants treated with the addition of glimepiride.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Ertugliflozin 5 mg
Drug: Ertugliflozin 10 mg
Drug: Glimerpiride
Drug: Placebo to Ertugliflozin
Drug: Placebo to Glimepiride
Drug: Metformin
Drug: Sitagliptin
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, Active-Comparator-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Ertugliflozin (MK-8835/PF-04971729) Compared With the Addition of Glimepiride in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin

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 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Number of Participants Experiencing An Adverse Event (AE) [ Time Frame: Up to Week 106 ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to Week 104 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Participants with an Adverse Event of Symptomatic Hypoglycemia [ Time Frame: Up to Week 52 ] [ Designated as safety issue: Yes ]
  • Change from Baseline in Body Weight at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Change from Baseline in Systolic Blood Pressure at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1230
Study Start Date: December 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ertugliflozin 5 mg
Participants randomized to ertugliflozin 5 mg once daily (q.d.) will take one ertugliflozin 5 mg tablet, one matching placebo tablet for ertugliflozin 10 mg, and matching placebo(s) for glimepiride daily from Day 1 to Week 104.
Drug: Ertugliflozin 5 mg
Ertugliflozin, 5 mg, oral, once daily, from Day 1 to Week 104
Other Name: MK-8835
Drug: Placebo to Ertugliflozin
Matching placebo to ertugliflozin, 5 mg and/or 10 mg, oral, once daily, from Day 1 to Week 104
Drug: Placebo to Glimepiride
Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104.
Drug: Metformin
The dose of metformin (>=1500 mg/day) should remain stable throughout the 104-week double-blind treatment period.
Drug: Sitagliptin
Open label, oral, once daily, rescue medication as required.
Experimental: Ertugliflozin 15 mg
Participants randomized to ertugliflozin 15 mg q.d. will take one 5 mg tablet and one 10 mg tablet of ertugliflozin and matching placebo(s) for glimepiride daily from Day 1 to Week 104.
Drug: Ertugliflozin 5 mg
Ertugliflozin, 5 mg, oral, once daily, from Day 1 to Week 104
Other Name: MK-8835
Drug: Ertugliflozin 10 mg
Ertugliflozin, 10 mg, oral, once daily from Day 1 to Week 104.
Drug: Placebo to Glimepiride
Matching placebo to glimepiride, 1 mg or 2 mg, oral, once daily, from Day 1 to Week 104.
Drug: Metformin
The dose of metformin (>=1500 mg/day) should remain stable throughout the 104-week double-blind treatment period.
Drug: Sitagliptin
Open label, oral, once daily, rescue medication as required.
Active Comparator: Glimepiride up to 8 mg
Participants randomized to glimepiride will take glimepiride tablets (1 and/or 2 mg) to a maximum of 8 mg and matching placebo tablets for ertugliflozin 5 mg and 10 mg daily from Day 1 to Week 104.
Drug: Glimerpiride
Glimepiride, oral tablets, initiated at 1 mg daily and titrated up to the maximum approved dose (8 mg daily based on the local country label) or maximum tolerated dose
Drug: Placebo to Ertugliflozin
Matching placebo to ertugliflozin, 5 mg and/or 10 mg, oral, once daily, from Day 1 to Week 104
Drug: Metformin
The dose of metformin (>=1500 mg/day) should remain stable throughout the 104-week double-blind treatment period.
Drug: Sitagliptin
Open label, oral, once daily, rescue medication as required.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of T2DM in accordance to American Diabetes Association guidelines
  • On metformin monotherapy or metformin in combination with a single allowable anti-hyperglycemic agent (AHA), dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, or alpha-glucosidase inhibitors) prior to study participation.
  • Body Mass Index (BMI) ≥18.0 kg/m^2
  • Male or female not of reproductive potential
  • If a female of reproductive potential, agree 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 or presence of type 1 diabetes mellitus or a history of ketoacidosis
  • History of other specific types of diabetes (eg, 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 2 (SGLT2) inhibitor
  • Use of the following prohibited therapeutic agents within 12 weeks of study participation: insulin, injectable anti-hyperglycemic agents, pioglitazone or rosiglitazone, another SGLT2 inhibitor, bromocriptine (Cycloset®), colesevelam (Welchol®), and any other non-approved anti-hyperglycemic therapy
  • Known hypersensitivity or intolerance to metformin or glimepiride
  • On a weight-loss program or medication or medication associated with weight changes and is not weight-stable (>=5% change in body weight in the last 6 months)
  • History of bariatric surgery less than 12 months prior to study participation
  • 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
  • Active, obstructive uropathy or an indwelling urinary catheter
  • 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)
  • Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells
  • A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C (assessed by medical history), primary biliary cirrhosis, or symptomatic gallbladder disease
  • Any clinically significant malabsorption condition
  • Being treated for hyperthyroidism, or on thyroid replacement therapy that has not been at a stable dose for at least 6 weeks prior to study participation
  • Previous randomization in a study with ertugliflozin
  • Participation in other studies involving investigational drug(s) within 30 days of study participation and/or during the pre-randomization period
  • A surgical procedure within 6 weeks prior to study participation or planned major surgery during the trial
  • A positive urine pregnancy test
  • Pregnant or breast-feeding, or expecting to conceive during the trial, including 14 days following the last dose of study drug
  • Undergoing hormonal therapy in preparation to donate eggs during the period of the trial, including 14 days following the last dose of study drug
  • Consumption of more than 2 alcoholic drinks per day or engages in binge drinking
  • Donation of 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: NCT01999218

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

  Show 62 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01999218     History of Changes
Other Study ID Numbers: 8835-002, 2013-003582-34
Study First Received: November 25, 2013
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glimepiride
Metformin
Anti-Arrhythmia Agents
Cardiovascular Agents
Hypoglycemic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014