A Study of the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Participants With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise (MK-8835-003)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01958671
First received: October 7, 2013
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

This trial will evaluate the efficacy and safety of ertugliflozin monotherapy in the treatment of subjects with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on diet and exercise. This trial consists of a run-in period of 3 to 11 weeks, a 26-week placebo-controlled treatment period (Phase A), and a 26-week active treatment period (Phase B). The primary hypothesis of the trial is that at Week 26, the mean reduction from baseline in hemoglobin A1c (HbA1c) for 15 mg ertugliflozin is greater than that for placebo.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Ertugliflozin (5 mg)
Drug: Ertugliflozin (10 mg)
Drug: Placebo to Ertuglifozin
Drug: Metformin
Drug: Placebo to Metformin
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 3, Randomized, Double-blind, Placebo-controlled, 26-week Multicenter Study With a 26-Week Extension to Evaluate the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change from Baseline In Hemoglobin A1c (HbA1c) 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 52 ] [ 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 ]

Secondary Outcome Measures:
  • 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 a HbA1c <7% (53 mmol/mol) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
  • Change from Baseline in 2-hour Post-prandial Plasma Glucose at Week 26 [ Time Frame: Baseline and 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 ]
  • Change from Baseline in Diastolic Blood Pressure at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]

Estimated Enrollment: 450
Study Start Date: October 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ertugliflozin (5 mg)
Once daily for a 26-week placebo-controlled treatment period of Phase A and for a 26-week active-controlled treatment period (Phase B). In Phase B, participants not rescued with open label metformin in Phase A, will also receive placebo to metformin. Participants rescued with metformin in Phase A will enter into Phase B and continue to receive open-label metformin in addition to their original randomized treatment.
Drug: Ertugliflozin (5 mg)
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
  • MK-8835
  • PF-04971729
Drug: Placebo to Ertuglifozin
One placebo tablet matching the ertugliflozin 5 mg tablet and/or 1 placebo tablet matching the ertugliflozin 10 mg tablet per day taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Drug: Placebo to Metformin
Placebo matching metformin.
Other Name: Glucophage XR, Carbophage SR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor and Metfogamma.
Experimental: Ertugliflozin (15 mg)
Once daily for a 26-week placebo-controlled treatment period of Phase A and for a 26-week active-controlled treatment period (Phase B). In Phase B, participants not rescued with open label metformin in Phase A, will also receive placebo to metformin. Participants rescued with metformin in Phase A will enter into Phase B and continue to receive open-label metformin in addition to their original randomized treatment.
Drug: Ertugliflozin (5 mg)
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
  • MK-8835
  • PF-04971729
Drug: Ertugliflozin (10 mg)
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
  • MK-8835
  • PF-04971729
Drug: Placebo to Metformin
Placebo matching metformin.
Other Name: Glucophage XR, Carbophage SR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor and Metfogamma.
Placebo Comparator: Placebo
Once daily for a 26-week placebo-controlled treatment period of Phase A. In Phase B, participants not rescued with open-labeled metformin in Phase A will also receive blinded metformin in addition to placebo. Participants rescued with metformin in Phase A will enter into Phase B and continue to receive open-label metformin in addition to their original randomized treatment.
Drug: Placebo to Ertuglifozin
One placebo tablet matching the ertugliflozin 5 mg tablet and/or 1 placebo tablet matching the ertugliflozin 10 mg tablet per day taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Drug: Metformin
500 mg (1 tablet) in the morning and 500 mg (1 tablet) in the evening for 2 weeks, 1000 mg (2 tablets 500 mg) in the morning and 500 mg (1 tablet) in the evening ) for 2 weeks and 1000 mg (2 tablets 500 mg ) in the morning and 1000 mg (2 tablets 500 mg) in the evening thereafter.

  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
  • Participants with no prior allowable oral anti-hyperglycemic agents (AHA) for at least 8 weeks prior to study participation or participants on a single allowable oral AHA at the start of study participation
  • Particpants on a single allowable AHA must be willing to discontinue this medication at the Screening Visit (S2) and remain off this medication for the duration of the trial. Allowable oral AHAs for discontinuation are metformin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides or alpha-glucosidase inhibitors.

Exclusion Criteria:

  • 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 clinically significant electrocardiogram abnormality
  • 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
  • A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor or metformin
  • On a blood pressure or lipid altering medication that have not been on a stable dose for at least 4 weeks prior to study participation
  • A surgical procedure within 4 weeks prior to study participation or planned major surgery during the trial
  • 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
  • Pregnant or breast-feeding, or is expecting to conceive during the trial, including 14 days following the last dose of study drug
  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: NCT01958671

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

  Show 21 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Pfizer
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01958671     History of Changes
Other Study ID Numbers: 8835-003, 2013-002519-90, B1521022
Study First Received: October 7, 2013
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014