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Trial record 1 of 1 for:    NCT02033889
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A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007).

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02033889
Recruitment Status : Completed
First Posted : January 13, 2014
Results First Posted : September 10, 2018
Last Update Posted : September 10, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE January 9, 2014
First Posted Date  ICMJE January 13, 2014
Results First Submitted Date  ICMJE June 20, 2018
Results First Posted Date  ICMJE September 10, 2018
Last Update Posted Date September 10, 2018
Actual Study Start Date  ICMJE December 13, 2013
Actual Primary Completion Date August 3, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
  • Change From Baseline in A1C at Week 26 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach) [ Time Frame: Up to Week 106 ]
    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Per protocol, participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or basal insulin according to Investigator judgment.
  • Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach) [ Time Frame: Up to Week 104 ]
    An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Per protocol, participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or basal insulin according to Investigator judgment.
Original Primary Outcome Measures  ICMJE
 (submitted: January 9, 2014)
  • Change from Baseline in Hemoglobin A1c [ Time Frame: Baseline and Week 26 ]
  • Number of Participants Experiencing An Adverse Event (AE) [ Time Frame: Up to Week 106 ]
  • Number of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to Week 104 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
  • Change From Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 26 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 26 minus FPG at Week 0) which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Body Weight at Week 26 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    The change in body weight from baseline reflects the Week 26 body weight minus the Week 0 body weight (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) [ Time Frame: Week 26 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    This change from baseline reflects the Week 26 sitting systolic blood pressure (SBP) minus the Week 0 sitting SBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    This change from baseline reflects the Week 26 sitting diastolic blood pressure (DBP) minus the Week 0 sitting DBP (which is estimated on average for each treatment group using a constrained longitudinal data analysis model, which allows for participants with missing data to be included in the analysis). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 26 (Logistic Regression Using Multiple Imputation: Excluding Rescue Approach) [ Time Frame: Week 26 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26 [ Time Frame: Up to Week 26 ]
    Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment.
  • Time to Glycemic Rescue Therapy at Week 26 [ Time Frame: Week 26 ]
    Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment.
  • Change From Baseline in A1C at Week 52 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 52 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy) [ Time Frame: Baseline and Week 52 ]
    Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 52 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 52 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 52 (Excluding Rescue Approach) [ Time Frame: Week 52 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 52 (Excluding Rescue Approach) [ Time Frame: Week 52 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52 [ Time Frame: Up to Week 52 ]
    Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment.
  • Change From Baseline in Body Weight at Week 52 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    The change in body weight from baseline reflects the Week 52 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    This change from baseline reflects the Week 52 sitting SBP minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    This change from baseline reflects the Week 52 sitting DBP minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in A1C at Week 104 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 104 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 104 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 104 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants With an A1C of <7% (53 mmol/Mol) at Week 104 (Excluding Rescue Approach) [ Time Frame: Week 104 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants With an A1C of <6.5% (48 mmol/Mol) at Week 104 (Excluding Rescue Approach) [ Time Frame: Week 104 ]
    A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104 [ Time Frame: Up to Week 104 ]
    Per protocol participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment.
  • Change From Baseline in Body Weight at Week 104 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    The change in body weight from baseline reflects the Week 104 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    This change from baseline reflects the Week 104 sitting SBP minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Change From Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    This change from baseline reflects the Week 104 sitting DBP minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) [ Time Frame: Pre-dose and/or 60 minutes post-dose on Weeks 6, 12, 18, and 30 ]
    Pharmacokinetic samples were collected at approximately 24 hours following the prior day's dose and before administration of the current day's dose. The lower limit of quantitation (LLOQ) was 0.500 mg/mL. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy.
  • Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    BMD at the femoral neck was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    BMD at the femoral neck was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    BMD at the total hip was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 26 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    BMD at the distal forearm was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) at Week 26 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 26 ]
    PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    BMD at the femoral neck was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    BMD at the femoral neck was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    BMD at the total hip was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 52 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    BMD at the distal forearm was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 52 ]
    PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    BMD at the femoral neck was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    BMD at the femoral neck was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in BMD at Week 104 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    BMD at the total hip was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From BMD at Week 104 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    BMD at the distal forearm was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker CTX at Week 104 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker P1NP at Week 104 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
  • Percent Change From Baseline in Bone Biomarker PTH at Week 104 (Excluding Bone Rescue Approach) [ Time Frame: Baseline and Week 104 ]
    PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2014)
  • Change from Baseline in Fasting Plasma Glucose [ 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 of <7% (53 mmol/mol) at Week 26 [ Time Frame: Week 26 ]
  • Change from Baseline in Systolic Blood Pressure [ Time Frame: Baseline and Week 26 ]
  • Change from Baseline in Diastolic Blood Pressure [ Time Frame: Baseline and Week 26 ]
  • Change from Baseline in Bone Mineral Density at Week 26 [ Time Frame: Baseline and Week 26 ]
  • Change from Baseline in Bone Mineral Density at Week 52 [ Time Frame: Baseline and Week 52 ]
  • Change from Baseline in Bone Mineral Density at Week 104 [ Time Frame: Baseline and Week 104 ]
  • Number of participants with HbA1c <=6.5% (48 mmol/mol) at Week 26 [ Time Frame: Week 26 ]
  • Number of participants requiring glycemic rescue therapy up to Week 26 [ Time Frame: Up to Week 26 ]
  • Time to glycemic rescue therapy up to Week 26 [ Time Frame: Up to Week 26 ]
  • Change from baseline in bone biomarkers at Week 26 [ Time Frame: Baseline and Week 26 ]
  • Change from baseline in bone biomarkers at Week 52 [ Time Frame: Baseline and Week 52 ]
  • Change from baseline in bone biomarkers at Week 104 [ Time Frame: Baseline and Week 104 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007).
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 26-Week Multicenter Study With a 78-Week Extension To Evaluate The Efficacy And Safety Of Ertugliflozin In Subjects With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy.
Brief Summary This is an efficacy and safety study of ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin monotherapy. The primary study hypothesis is that at Week 26, the mean reduction from baseline in hemoglobin A1c (HbA1c) for ertugliflozin is greater than that for placebo.
Detailed Description The trial includes a 13-15 week run-in period prior to randomization, and a 26-week, double-blind, placebo-controlled treatment period followed by a 78-week double-blind, extension period.
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
    Ertugliflozin 5 mg orally (1 ertugliflozin 5 mg tablet and 1 placebo ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.
    Other Name: MK-8835
  • Drug: Ertugliflozin 15 mg
    Ertugliflozin 15 mg orally (1 ertugliflozin 5 mg tablet and 1 ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.
    Other Name: MK-8835
  • Drug: Placebo to Ertugliflozin
    Placebo to ertuglioflozin (1 placebo ertugliflozin 5 mg tablet and/or 1 placebo ertugliflozin 10 mg tablet), orally once daily from Day 1 to Week 104.
  • Other: Glimepiride
    Open-label Glimepiride will be used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) in the 26-week initial period. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period.
    Other Names:
    • Amaryl
    • GLIMPID
    • GLIMY
  • Drug: Placebo to Glimepiride
    Placebo to glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of placebo to glimepiride is at the discretion of the investigator.
  • Biological: Basal Insulin
    Basal insulin will be administered in the initial 26-week period for participants with glucose values exceeding protocol-specified values and for participants requiring rescue therapy in the 78-week extension period. Dosing and titration of basal insulin is at the discretion of the Investigator.
    Other Names:
    • Insulin glargine
    • Insulin detemir
    • NPH insulin
    • Degludec
  • Drug: Metformin
    Metformin >=1500 mg/day, orally, once a day
    Other Names:
    • Glucophage XR
    • Carbophage SR
    • Riomet
    • Fortamet
    • Glumetza
    • Obimet
    • Gluformin
    • Dianben
    • Diabex
    • Diaformin
    • Siofor
    • Metfogamma
Study Arms  ICMJE
  • Experimental: Ertuglifozin 5 mg
    Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.
    Interventions:
    • Drug: Ertugliflozin 5 mg
    • Drug: Placebo to Ertugliflozin
    • Other: Glimepiride
    • Drug: Placebo to Glimepiride
    • Biological: Basal Insulin
    • Drug: Metformin
  • Experimental: Ertugliflozin 15 mg
    Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.
    Interventions:
    • Drug: Ertugliflozin 15 mg
    • Other: Glimepiride
    • Drug: Placebo to Glimepiride
    • Biological: Basal Insulin
    • Drug: Metformin
  • Placebo Comparator: Placebo/Glimepiride
    Placebo to ertugliflozin, orally once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received blinded glimepiride. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.
    Interventions:
    • Drug: Placebo to Ertugliflozin
    • Other: Glimepiride
    • Biological: Basal Insulin
    • Drug: Metformin
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: August 28, 2017)
621
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2014)
600
Actual Study Completion Date  ICMJE August 3, 2017
Actual Primary Completion Date August 3, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of T2DM in accordance to American Diabetes Association guidelines
  • Participants must be receiving metformin monotherapy for less than 8 weeks prior to study participation or require change in their diabetes regimen to remain eligible to participate in the trial (including discontinuing anti-hyperglycemic agent [AHA] therapy) and must have a hemoglobin A1c of 7.0 to 10.5% (53-91 mmol/mol) after at least 8 weeks on a regimen of metformin monotherapy

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 glimepiride
  • 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 6 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 Australia,   Czech Republic,   Hong Kong,   Hungary,   Israel,   Mexico,   Poland,   Romania,   Russian Federation,   Slovakia,   South Africa,   Taiwan,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02033889
Other Study ID Numbers  ICMJE 8835-007
2013-003290-95 ( EudraCT Number )
B1521017 ( Other Identifier: Pfizer Protocol Number )
MK-8835-007 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
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 August 2018

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