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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, VERTIS MONO)

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ClinicalTrials.gov Identifier: NCT01958671
Recruitment Status : Completed
First Posted : October 9, 2013
Results First Posted : September 29, 2017
Last Update Posted : September 29, 2017
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE October 7, 2013
First Posted Date  ICMJE October 9, 2013
Results First Submitted Date  ICMJE July 14, 2017
Results First Posted Date  ICMJE September 29, 2017
Last Update Posted Date September 29, 2017
Actual Study Start Date  ICMJE October 9, 2013
Actual Primary Completion Date July 28, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2017)
  • Change From Baseline In A1C at Week 26 [ Time Frame: Baseline and Week 26 ]
    A1C is measured as percent. The change from baseline is the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
  • Percentage of Participants Experiencing An Adverse Event (AE) [ Time Frame: Up to 54 weeks (including 2 weeks following last dose) ]
    An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
  • Percentage of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to 52 weeks ]
    An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2013)
  • Change from Baseline In Hemoglobin A1c (HbA1c) at Week 26 [ Time Frame: Baseline and Week 26 ]
  • Number of Participants Experiencing An Adverse Event (AE) [ Time Frame: Up to Week 52 ]
  • Number of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2017)
  • Change From Baseline in FPG at Week 26 [ Time Frame: Baseline and Week 26 ]
    The change from baseline is the Week 26 FPG minus the Week 0 FPG. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of glycemic rescue therapy.
  • Change From Baseline in Body Weight at Week 26 [ Time Frame: Baseline and Week 26 ]
    The change from baseline is the Week 26 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy.
  • Percentage of Participants With A1C <7% (<53 mmol/Mol) at Week 26 [ Time Frame: Week 26 ]
    A1C is measured as percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
  • Baseline 2-hour Post-prandial Glucose (2-hr PPG) Level [ Time Frame: Baseline ]
    Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the Mixed Meal Tolerance Test (MMTT). Change from baseline in 2-hr PPG level at Week 26 data are presented in the following outcome measure.
  • Change From Baseline in 2-hr PPG at Week 26 [ Time Frame: Baseline and Week 26 ]
    The change from baseline is the Week 26 2-hr PPG minus the Week 0 2-hr PPG. Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the MMTT. Data presented exclude data following the initiation of rescue therapy.
  • Baseline Sitting Systolic Blood Pressure (SBP) [ Time Frame: Baseline ]
    Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in SBP at Week 26 data are presented in the following outcome measure.
  • Change From Baseline in SBP at Week 26 [ Time Frame: Baseline and Week 26 ]
    The change from baseline is the Week 26 SBP minus the Week 0 SBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy.
  • Baseline Sitting Diastolic Blood Pressure (DBP) [ Time Frame: Baseline ]
    Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in DBP at Week 26 data are presented in the following outcome measure.
  • Change From Baseline in DBP at Week 26 [ Time Frame: Baseline and Week 26 ]
    The change from baseline is the Week 26 DBP minus the Week 0 DBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2013)
  • Change from Baseline in Fasting Plasma Glucose (FPG) at Week 26 [ Time Frame: Baseline and Week 26 ]
  • Change From Baseline in Body Weight at Week 26 [ Time Frame: Baseline and Week 26 ]
  • Number of Participants with a HbA1c <7% (53 mmol/mol) at Week 26 [ Time Frame: Week 26 ]
  • Change from Baseline in 2-hour Post-prandial Plasma Glucose at Week 26 [ Time Frame: Baseline and Week 26 ]
  • Change from Baseline in Systolic Blood Pressure at Week 26 [ Time Frame: Baseline and Week 26 ]
  • Change from Baseline in Diastolic Blood Pressure at Week 26 [ Time Frame: Baseline and Week 26 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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, VERTIS MONO)
Official Title  ICMJE 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
Brief Summary This trial will evaluate the efficacy and safety of ertugliflozin monotherapy in the treatment of participants 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 hypotheses of the trial are that at Week 26, the mean reduction from baseline in hemoglobin A1c (A1C) for 15 mg ertugliflozin is greater than that for placebo and the mean reduction from baseline in A1C for 5 mg ertugliflozin is greater than that for placebo.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • 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 Ertugliflozin
    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.
    Other Name: Glucophage XR, Carbophage SR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor and Metfogamma.
  • Drug: Placebo to Metformin
    1 tablet in the morning and 1 tablet in the evening for 2 weeks, 2 tablets in the morning and 1 tablet in the evening for 2 weeks and 2 tablets in the morning and 2 tablets in the evening, thereafter.
  • Drug: Glimepiride
    Dosing and titration of glimepiride as rescue therapy was determined by the investigator.
Study Arms  ICMJE
  • Experimental: Ertugliflozin 5 mg/Ertugliflozin 5 mg
    Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
    Interventions:
    • Drug: Ertugliflozin 5 mg
    • Drug: Placebo to Ertugliflozin
    • Drug: Metformin
    • Drug: Placebo to Metformin
    • Drug: Glimepiride
  • Experimental: Ertugliflozin 15 mg/Ertugliflozin 15 mg
    Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
    Interventions:
    • Drug: Ertugliflozin 5 mg
    • Drug: Ertugliflozin 10 mg
    • Drug: Metformin
    • Drug: Placebo to Metformin
    • Drug: Glimepiride
  • Placebo/Metformin
    Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
    Interventions:
    • Drug: Placebo to Ertugliflozin
    • Drug: Metformin
    • Drug: Glimepiride
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 1, 2017)
461
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2013)
450
Actual Study Completion Date  ICMJE July 28, 2016
Actual Primary Completion Date July 28, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Participants 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Canada,   Israel,   Italy,   Mexico,   South Africa,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT01958671
Other Study ID Numbers  ICMJE 8835-003
2013-002519-90 ( EudraCT Number )
B1521022 ( Other Identifier: Pfizer Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP