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.
Verified April 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: April 1, 2014
Last verified: April 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01986881

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

  Show 42 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: April 1, 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 April 16, 2014