- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02033889
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).
August 9, 2018 updated by: Merck Sharp & Dohme LLC
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.
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.
Study Overview
Status
Completed
Conditions
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
Interventional
Enrollment (Actual)
621
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
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 Names:
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.
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:
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.
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:
Metformin >=1500 mg/day, orally, once a day
Other Names:
|
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.
|
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:
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.
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:
Metformin >=1500 mg/day, orally, once a day
Other Names:
Ertugliflozin 15 mg orally (1 ertugliflozin 5 mg tablet and 1 ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.
Other Names:
|
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.
|
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.
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:
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:
Metformin >=1500 mg/day, orally, once a day
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline and Week 26
|
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.
|
Up to Week 106
|
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.
|
Up to Week 104
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Week 26
|
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.
|
Up to Week 26
|
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.
|
Week 26
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Week 52
|
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.
|
Week 52
|
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.
|
Up to Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Week 104
|
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.
|
Week 104
|
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.
|
Up to Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Pre-dose and/or 60 minutes post-dose on Weeks 6, 12, 18, and 30
|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 26
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 52
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
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.
|
Baseline and Week 104
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.
- Gallo S, Calle RA, Terra SG, Pong A, Tarasenko L, Raji A. Effects of Ertugliflozin on Liver Enzymes in Patients with Type 2 Diabetes: A Post-Hoc Pooled Analysis of Phase 3 Trials. Diabetes Ther. 2020 Aug;11(8):1849-1860. doi: 10.1007/s13300-020-00867-1. Epub 2020 Jul 9.
- Patel S, Hickman A, Frederich R, Johnson S, Huyck S, Mancuso JP, Gantz I, Terra SG. Safety of Ertugliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Seven Phase 3 Randomized Controlled Trials. Diabetes Ther. 2020 Jun;11(6):1347-1367. doi: 10.1007/s13300-020-00803-3. Epub 2020 May 5.
- Liu J, Tarasenko L, Pong A, Huyck S, Wu L, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Aug;36(8):1277-1284. doi: 10.1080/03007995.2020.1760228. Epub 2020 May 13.
- Liu J, Tarasenko L, Pong A, Huyck S, Patel S, Hickman A, Mancuso JP, Ellison MC, Gantz I, Terra SG. Efficacy and safety of ertugliflozin in Hispanic/Latino patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Jul;36(7):1097-1106. doi: 10.1080/03007995.2020.1760227. Epub 2020 May 13.
- Liu J, Patel S, Cater NB, Wu L, Huyck S, Terra SG, Hickman A, Darekar A, Pong A, Gantz I. Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2020 Apr;22(4):574-582. doi: 10.1111/dom.13931. Epub 2020 Jan 3.
- Liu J, Pong A, Gallo S, Darekar A, Terra SG. Effect of ertugliflozin on blood pressure in patients with type 2 diabetes mellitus: a post hoc pooled analysis of randomized controlled trials. Cardiovasc Diabetol. 2019 May 7;18(1):59. doi: 10.1186/s12933-019-0856-7.
- Cherney DZI, Heerspink HJL, Frederich R, Maldonado M, Liu J, Pong A, Xu ZJ, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Effects of ertugliflozin on renal function over 104 weeks of treatment: a post hoc analysis of two randomised controlled trials. Diabetologia. 2020 Jun;63(6):1128-1140. doi: 10.1007/s00125-020-05133-4. Epub 2020 Mar 31.
- Rosenstock J, Frias J, Pall D, Charbonnel B, Pascu R, Saur D, Darekar A, Huyck S, Shi H, Lauring B, Terra SG. Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET). Diabetes Obes Metab. 2018 Mar;20(3):520-529. doi: 10.1111/dom.13103. Epub 2017 Oct 2. Erratum In: Diabetes Obes Metab. 2018 Nov;20(11):2708.
- Gallo S, Charbonnel B, Goldman A, Shi H, Huyck S, Darekar A, Lauring B, Terra SG. Long-term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104-week VERTIS MET trial. Diabetes Obes Metab. 2019 Apr;21(4):1027-1036. doi: 10.1111/dom.13631. Epub 2019 Feb 14.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 13, 2013
Primary Completion (Actual)
August 3, 2017
Study Completion (Actual)
August 3, 2017
Study Registration Dates
First Submitted
January 9, 2014
First Submitted That Met QC Criteria
January 9, 2014
First Posted (Estimate)
January 13, 2014
Study Record Updates
Last Update Posted (Actual)
September 10, 2018
Last Update Submitted That Met QC Criteria
August 9, 2018
Last Verified
August 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Immunosuppressive Agents
- Immunologic Factors
- Sodium-Glucose Transporter 2 Inhibitors
- Insulin
- Insulin, Globin Zinc
- Metformin
- Insulin Glargine
- Glimepiride
- Ertugliflozin
- Insulin Detemir
Other Study ID Numbers
- 8835-007
- 2013-003290-95 (EudraCT Number)
- B1521017 (Other Identifier: Pfizer Protocol Number)
- MK-8835-007 (Other Identifier: Merck Protocol Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 2 Diabetes Mellitus
-
SanofiCompletedType 1 Diabetes Mellitus-Type 2 Diabetes MellitusHungary, Russian Federation, Germany, Poland, Japan, United States, Finland
-
Mannkind CorporationTerminatedType 2 Diabetes Mellitus | Type 1 Diabetes MellitusUnited States
-
RWTH Aachen UniversityBoehringer IngelheimCompletedDiabetes Mellitus Type 2 (T2DM)Germany
-
Griffin HospitalCalifornia Walnut CommissionCompletedDIABETES MELLITUS TYPE 2United States
-
University Hospital Inselspital, BerneCompletedType 2 Diabetes MellitusSwitzerland
-
India Diabetes Research Foundation & Dr. A. Ramachandran...CompletedTYpe 2 Diabetes MellitusIndia
-
Scripps Whittier Diabetes InstituteSan Diego State UniversityCompletedType 2 Diabetes Mellitus (T2DM)United States
-
AstraZenecaRecruiting
-
Daewoong Pharmaceutical Co. LTD.Not yet recruitingT2DM (Type 2 Diabetes Mellitus)
-
Zhongda HospitalRecruitingType 2 Diabetes Mellitus (T2DM)China
Clinical Trials on Ertugliflozin 5 mg
-
Merck Sharp & Dohme LLCPfizerActive, not recruitingType 2 Diabetes MellitusUnited States, Belgium, Canada, Colombia, Costa Rica, Dominican Republic, France, Guatemala, Hungary, Israel, Italy, Malaysia, Mauritius, Mexico, Philippines, Poland, Russian Federation, Saudi Arabia, Turkey, Ukraine, United Arab... and more
-
Merck Sharp & Dohme LLCPfizerCompleted
-
Merck Sharp & Dohme LLCPfizerCompletedHypertension | Diabetes Mellitus, Type 2
-
Merck Sharp & Dohme LLCPfizerCompleted
-
Merck Sharp & Dohme LLCPfizerCompleted
-
Merck Sharp & Dohme LLCPfizerCompleted
-
Getz PharmaNot yet recruitingBody Weight Changes | Liver Fat | Tolerance | Liver Fibrosis | Glycemic Control | Waist Circumference
-
University Hospitals Cleveland Medical CenterTerminatedDiabetes Mellitus, Type 2 | Heart Failure, DiastolicUnited States
-
Medical University of GrazMedical University of Vienna; Landesklinkum Wiener Neustadt; Klinik Ottakring; Medical... and other collaboratorsTerminatedImplantable Cardioverter-Defibrillators | Heart Failure With Reduced Ejection Fraction | Cardiac Resynchronization Therapy | Heart Failure With Mid Range Ejection FractionAustria
-
Merck Sharp & Dohme LLCPfizerCompletedType 2 Diabetes Mellitus