Cardiovascular Outcomes Following Treatment With Ertugliflozin in Participants With Type 2 Diabetes Mellitus and Established Vascular Disease (MK-8835-004)

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:
NCT01986881
First received: November 12, 2013
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

A study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial includes a pre-defined glycemic sub-study in participants receiving background insulin with or without metformin and another pre-defined glycemic sub-study in participants receiving background sulfonylurea monotherapy.


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: Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess Cardiovascular Outcomes Following Treatment With Ertugliflozin (MK-8835/PF-04971729) in Subjects With Type 2 Diabetes Mellitus and Established Vascular Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to First Occurrence of Any Component of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke [ Time Frame: Up to 6.3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to First Occurrence of any of the Components of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke or Hospitalization for Unstable Angina [ Time Frame: Up to 6.3 years ] [ Designated as safety issue: Yes ]
  • Number of Participants Experiencing An Adverse Event (AE) [ Time Frame: Up to 6.3 years ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to 6.3 years ] [ Designated as safety issue: Yes ]
  • Change from Baseline In Hemoglobin A1c (HbA1c) at Week 18 [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]
  • Change from Baseline In HbA1c at the End of Study (up to 6.3 years) [ Time Frame: Baseline and at the End of Study (up to 6.3 years) ] [ Designated as safety issue: No ]
  • Change from Baseline in Fasting Plasma Glucose (FPG) at Week 18 [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]
  • Change from Baseline in Body Weight at Week 18 [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]
  • Change from Baseline in Body Weight at the End of Study (up to 6.3 years) [ Time Frame: Baseline and at the End of Study (up to 6.3 years) ] [ Designated as safety issue: No ]
  • Number of Participants with a HbA1c <7% at Week 18 [ Time Frame: Week 18 ] [ Designated as safety issue: No ]
  • Number of Participants with a HbA1c <7% at the End of Study (up to 6.3 years) [ Time Frame: At the End of Study (up to 6.3 years) ] [ Designated as safety issue: No ]
  • Change from Baseline in Systolic Blood Pressure at Week 18 [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]
  • Change from Baseline in Systolic Blood Pressure at the End of Study (up to 6.3 years) [ Time Frame: Baseline and at the End of Study (up to 6.3 years) ] [ Designated as safety issue: No ]
  • Change from Baseline in Diastolic Blood Pressure at Week 18 [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]
  • Change from Baseline in Diastolic Blood Pressure at the End of Study (up to 6.3 years) [ Time Frame: Baseline and at the End of Study (up to 6.3 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 3900
Study Start Date: November 2013
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ertugliflozin, 15 mg
Ertugliflozin 15 mg administered orally once daily for up to 6.3 years
Drug: Ertugliflozin
Oral, once daily, up to 6.3 years
Other Name: MK-8835
Experimental: Ertugliflozin, 5 mg
Ertugliflozin 5 mg administered orally once daily for up to 6.3 years
Drug: Ertugliflozin
Oral, once daily, up to 6.3 years
Other Name: MK-8835
Drug: Placebo
Matching placebo to ertugliflozin administered orally once daily for up to 6.3 years
Placebo Comparator: Placebo
Matching placebo to ertugliflozin administered orally once daily for up to 6.3 years
Drug: Placebo
Matching placebo to ertugliflozin administered orally once daily for up to 6.3 years

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines
  • Hemoglobin A1c (HbA1c) at the start of study participation of 7.0-10.5% (53-91 mmol/mol)
  • On stable allowable anti-hyperglycemic agents (AHA) or on no background AHA for at least 8 weeks prior to the study participation
  • Body Mass Index (BMI) > or = to 18.0 kg/m^2
  • Evidence or a history of atherosclerosis involving the coronary, cerebral or peripheral vascular systems
  • Male, female not or reproductive potential, or female of reproductive potential who agrees to be abstinent from heterosexual activity or agrees to use or have their partner use 2 acceptable methods of contraception
  • Additional Inclusion Criteria Specific to the Insulin +/- Metformin Add-on Glycemic Sub-Study
  • Insulin >=20 units/day with or without metformin >=1,500 mg/day stable doses for at least 8 weeks prior to study participation
  • Additional Inclusion Criteria Specific to the sulfonylurea (SU) Monotherapy Add-on Glycemic Sub-Study
  • Monotherapy with an acceptable dose of a SU. The dose of the SU monotherapy must have been stable for at least 8 weeks prior to study participation.

Exclusion Criteria:

  • Previous randomization into a trial of ertugliflozin
  • Experiencing a cardiovascular event (myocardial infarction or stroke) or undergoing coronary angioplasty or peripheral intervention procedure between the Screening Visit and randomization
  • Undergoing any cardiovascular surgery (valvular surgery) within 3 months of study participation
  • Planned revascularization or peripheral intervention procedure or other cardiovascular surgery
  • New York Heart Association (NYHA) Class III or IV heart failure at study participation
  • History of type 1 diabetes mellitus or a history of ketoacidosis
  • Additional Exclusion Criteria Specific to the Insulin +/- Metformin Add-on Glycemic Sub-Study
  • Use of prandial insulin alone without basal insulin
  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: NCT01986881

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

  Show 116 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Pfizer
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01986881     History of Changes
Other Study ID Numbers: 8835-004, 2013-002518-11
Study First Received: November 12, 2013
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 25, 2014