Ertugliflozin and Sitagliptin Co-administration Factorial Study (MK-8835-005)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02099110
First received: March 25, 2014
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

This is a study of co-administration of ertugliflozin (MK-8835/PF-04971729) and sitagliptin given together or alone along with metformin in participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin monotherapy. The primary hypothesis of this study is that ertugliflozin 15 mg daily plus sitagliptin 100 mg daily provides greater hemoglobin A1C (A1C)-lowering compared with sitagliptin 100 mg daily alone.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Matching Placebo to Ertugliflozin 5 mg
Drug: Matching Placebo to Ertugliflozin 10 mg
Drug: Matching Placebo to sitagliptin 100 mg
Drug: Ertugliflozin 5 mg
Drug: Ertugliflozin 10 mg
Drug: Sitagliptin 100 mg
Drug: Metformin >= 1500 mg/day
Biological: Insulin Glargine Rescue Medication
Drug: Glimepiride Rescue Medication
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, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin Compared With Ertugliflozin Alone and Sitagliptin Alone, in the Treatment of Subjects With T2DM With Inadequate Glycemic Control on Metformin Monotherapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change from Baseline in A1C [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to 54 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Discontinue Study Medication due to an AE [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from Baseline in Body Weight [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Change from Baseline in Fasting Plasma Glucose [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Change from Baseline in Systolic Blood Pressure [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Percentage of Participants Achieving a Hemoglobin A1C of <7% [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
  • Change from Baseline in Parameters of Beta-cell Function [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1250
Study Start Date: April 2014
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ertugliflozin 5 mg + sitagliptin 100 mg
Ertugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks
Drug: Matching Placebo to Ertugliflozin 10 mg
Placebo to ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Drug: Ertugliflozin 5 mg
Ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Names:
  • MK-8835
  • PF-04971729
Drug: Sitagliptin 100 mg
Sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Name: JANUVIA®
Drug: Metformin >= 1500 mg/day
Metformin >= 1500 mg/day, tablets, oral, for 52 weeks while receiving blinded investigational product during the double-blind treatment period
Other Names:
  • Glucophage
  • Glucophage XR
Biological: Insulin Glargine Rescue Medication
Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion
Other Name: Lantus
Drug: Glimepiride Rescue Medication
Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion
Other Name: AMARYL
Experimental: Ertugliflozin 15 mg + sitagliptin 100 mg
Ertugliflozin 15 mg + sitagliptin 100 mg, oral, once daily for 52 weeks
Drug: Ertugliflozin 5 mg
Ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Names:
  • MK-8835
  • PF-04971729
Drug: Ertugliflozin 10 mg
Ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Names:
  • MK-8835
  • PF-04971729
Drug: Sitagliptin 100 mg
Sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Name: JANUVIA®
Drug: Metformin >= 1500 mg/day
Metformin >= 1500 mg/day, tablets, oral, for 52 weeks while receiving blinded investigational product during the double-blind treatment period
Other Names:
  • Glucophage
  • Glucophage XR
Biological: Insulin Glargine Rescue Medication
Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion
Other Name: Lantus
Drug: Glimepiride Rescue Medication
Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion
Other Name: AMARYL
Experimental: Ertugliflozin 5 mg
Ertugliflozin 5 mg, oral, once daily for 52 weeks
Drug: Matching Placebo to Ertugliflozin 10 mg
Placebo to ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Drug: Matching Placebo to sitagliptin 100 mg
Placebo to sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Drug: Ertugliflozin 5 mg
Ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Names:
  • MK-8835
  • PF-04971729
Drug: Metformin >= 1500 mg/day
Metformin >= 1500 mg/day, tablets, oral, for 52 weeks while receiving blinded investigational product during the double-blind treatment period
Other Names:
  • Glucophage
  • Glucophage XR
Biological: Insulin Glargine Rescue Medication
Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion
Other Name: Lantus
Drug: Glimepiride Rescue Medication
Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion
Other Name: AMARYL
Experimental: Ertugliflozin 15 mg
Ertugliflozin, oral, once daily for 52 weeks
Drug: Matching Placebo to sitagliptin 100 mg
Placebo to sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Drug: Ertugliflozin 5 mg
Ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Names:
  • MK-8835
  • PF-04971729
Drug: Ertugliflozin 10 mg
Ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Names:
  • MK-8835
  • PF-04971729
Drug: Metformin >= 1500 mg/day
Metformin >= 1500 mg/day, tablets, oral, for 52 weeks while receiving blinded investigational product during the double-blind treatment period
Other Names:
  • Glucophage
  • Glucophage XR
Biological: Insulin Glargine Rescue Medication
Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion
Other Name: Lantus
Drug: Glimepiride Rescue Medication
Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion
Other Name: AMARYL
Active Comparator: Sitagliptin 100 mg
Sitagliptin 100 mg, oral, once daily for 52 weeks
Drug: Matching Placebo to Ertugliflozin 5 mg
Placebo to ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Drug: Matching Placebo to Ertugliflozin 10 mg
Placebo to ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Drug: Sitagliptin 100 mg
Sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period
Other Name: JANUVIA®
Drug: Metformin >= 1500 mg/day
Metformin >= 1500 mg/day, tablets, oral, for 52 weeks while receiving blinded investigational product during the double-blind treatment period
Other Names:
  • Glucophage
  • Glucophage XR
Biological: Insulin Glargine Rescue Medication
Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion
Other Name: Lantus
Drug: Glimepiride Rescue Medication
Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion
Other Name: AMARYL

Detailed Description:

This study will include a 1-week screening period; an up to 12-week metformin titration/dose stabilization period; a 2-week single-blind placebo run-in period; a 52-week (26-week Phase A and (26-week Phase B) double-blind treatment period and a post-treatment telephone contact 14 days after the last dose of study medication.

  Eligibility

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

Inclusion Criteria:

  • Type 2 diabetes mellitus as per American Diabetes Association guidelines
  • On metformin monotherapy (>=1500 mg/day) for >=8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy (>=1500 mg/day) for <8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy <1500 mg/day with a Visit 1/Screening A1C >=8.0% and <=11.5% (>=64 mmol/mol and <=102 mmol/mol)
  • Body mass index (BMI) >=18.0 kg/m^2
  • Male or female not of reproductive potential
  • Female of reproductive potential who agrees to remain abstinent from heterosexual activity or to use 2 acceptable combinations of contraception

Exclusion Criteria:

  • History of type 1 diabetes mellitus or ketoacidosis
  • History of other specific types of diabetes (e.g., 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 (SGLT2) inhibitor or sitagliptin
  • Has been treated with any of the following agents within 12 weeks of study start or during the pre-randomization period: Insulin of any type (except for short-term use [i.e., <=7 days] during concomitant illness or other stress), other injectable anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other sodium glucose co-transporter 2 (SGLT2) inhibitors, alpha glucosidase inhibitors or meglitinides, dipeptidyl-peptidase 4 inhibitor (DPP-4 inhibitor), sulfonylureas (SUs), bromocriptine (Cycloset™), colesevelam (Welchol™), any other AHA with the exception of the protocol-approved agents
  • Is on a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable prior to study start
  • Has undergone bariatric surgery within the past 12 months or >12 months and is not weight stable prior to study start
  • A 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 start
  • Active, obstructive uropathy or indwelling urinary catheter
  • History of malignancy <=5 years prior to study start, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
  • A known history of human immunodeficiency virus (HIV)
  • A blood dyscrasia or any disorder causing hemolysis or unstable red blood cells, or a clinically important hematological disorder (e.g. 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 symptomatic gallbladder disease
  • Any clinically significant malabsorption condition
  • Current treatment for hyperthyroidism
  • On thyroid replacement therapy and not on a stable dose for at least 6 weeks prior study start
  • On a previous clinical study with ertugliflozin
  • eGFR (using the 4-variable Modification of Diet in Renal Disease Study Equation (MDRD) equation) <60 mL/min/1.73 m^2
  • Serum creatinine >= 1.3 mg/dL (115 µmol/L) for males and >= 1.2 mg/dL (106 µmol/L) for females
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times upper limit of normal
  • Hemoglobin <12 g/dL (120 g/L) for males and <11 g/dL (110 g/L) for females.
  • Participated in other studies involving investigational drug(s) 30 days prior to study start
  • Surgical procedure within 6 weeks prior to study start or major surgery planned during the trial
  • Positive urine pregnancy test
  • Pregnant or breast-feeding, or planning to conceive during the trial, including 14 days following the last dose of study medication
  • Planning to undergo hormonal therapy in preparation for egg donation during the trial, including 14 days following the last dose of study medication
  • Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or engages in binge drinking
  • Donated blood or blood products within 6 weeks of study start
  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: NCT02099110

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

  Show 44 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: NCT02099110     History of Changes
Other Study ID Numbers: 8835-005
Study First Received: March 25, 2014
Last Updated: September 4, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 16, 2014