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Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2)

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ertugliflozin 5 mg
Ertugliflozin 15 mg
Placebo for ertugliflozin 5 mg
Metformin
Sitagliptin
Glimepiride
Insulin
Placebo for ertugliflozin 10 mg
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of type 2 diabetes mellitus (T2DM)
  • On stable diabetes therapy of metformin with either sitagliptin or another dipeptidyl peptidase-4 (DPP-4) inhibitor or a sulfonylurea (SU) prior to study participation and is willing to wash-off/switch from another DPP-4 inhibitor/SU to sitagliptin
  • Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2
  • Male, postmenopausal female or surgically sterile female
  • If a female of reproductive potential, agrees to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug

Exclusion Criteria:

  • History of type 1 diabetes mellitus or a history of ketoacidosis
  • History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrine disorders, drug- or chemical-induced, and post-organ transplant)
  • A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) or DPP-4 inhibitor
  • On a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable
  • Has undergone bariatric surgery within the past 12 months or >12 months and is not weight stable
  • Has been treated with insulin (except for short-term use [<= 7 days]), injectable antihyperglycemic agents (AHAs) (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other sodium-glucose co-transporter 2 (SGLT2) inhibitors, alpha glucosidase inhibitors or meglitinides, bromocriptine (Cycloset™), colesevelam (Welchol™), or any other non-protocol approved AHAs within 12 weeks of study participation
  • Has active, obstructive uropathy or indwelling urinary catheter
  • 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 history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer
  • Known history of Human Immunodeficiency Virus (HIV)
  • Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or any other clinically significant hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
  • A medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease
  • Has any clinically significant malabsorption condition
  • If taking thyroid replacement therapy, has not been on a stable dose for at least 6 weeks prior to study participation
  • Has been previously randomized in a study with ertugliflozin
  • Has participated in other studies involving an investigational drug within 30 days prior or during study participation
  • Has undergone a surgical procedure within 6 weeks prior to or planned major surgery during study participation
  • Has a positive urine pregnancy test
  • Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of study medication
  • Planning to undergo hormonal therapy in preparation to donate eggs during the trial, including 14 days following the last dose of study medication
  • Excessive consumption of alcoholic beverages or binge drinking
  • Has donated blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Ertugliflozin 5 mg

    Ertugliflozin 15 mg

    Placebo

    Arm Description

    Ertugliflozin, 5 mg, oral, once daily for 52 weeks

    Ertugliflozin, 15 mg, oral, once daily for 52 weeks

    Matching placebo to ertuglifozin, oral, once daily for 52 weeks

    Outcomes

    Primary Outcome Measures

    Change From Baseline in Hemoglobin A1C at Week 26
    A1C is measured as percent. Thus this change from baseline reflects 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)
    An adverse event is defined as any untoward medical occurrence in a participant 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
    An adverse event is defined as any untoward medical occurrence in a participant 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.

    Secondary Outcome Measures

    Change From Baseline in Fasting Plasma Glucose (FPG) at 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 rescue therapy.
    Change From Baseline in Body Weight at 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 an A1C <7% (53 mmol/Mol) at 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.
    Change From Baseline in Sitting Systolic Blood Pressure at Week 26
    The change from baseline is the Week 26 systolic blood pressure minus the Week 0 systolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.
    Change From Baseline in Hemoglobin A1C at Week 52
    A1C is measured as percent. Thus this change from baseline reflects the Week 52 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.
    Change From Baseline in FPG at Week 52
    The change from baseline is the Week 52 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 rescue therapy.
    Change From Baseline in Body Weight at Week 52
    The change from baseline is the Week 52 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy.
    Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 52
    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.
    Change From Baseline in Sitting Systolic Blood Pressure at Week 52
    The change from baseline is the Week 52 systolic blood pressure minus the Week 0 systolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.
    Change From Baseline in Sitting Diastolic Blood Pressure at Week 26
    The change from baseline is the Week 26 diastolic blood pressure minus the Week 0 diastolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.
    Change From Baseline in Sitting Diastolic Blood Pressure at Week 52
    The change from baseline is the Week 52 diastolic blood pressure minus the Week 0 diastolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.
    Percentage of Participants Receiving Glycemic Rescue Medication by Week 26
    Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant).
    Percentage of Participants Receiving Glycemic Rescue Medication by Week 52
    Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant).
    Time to Initiation of Glycemic Rescue by Week 26
    Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant). Data presented are the minimum and maximum times to the initiation of rescue therapy in days. Below data include data from 1 participant in the Placebo arm who continued Phase A treatment for an additional 30 days.
    Time to Initiation of Glycemic Rescue by Week 52
    Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant). Data presented are the minimum and maximum times to the initiation of rescue therapy in days.
    Baseline Homeostasis Model Assessment of β-cell Function (HOMA-%β) Value
    HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = [20 x fasting insulin (μU/mL)] / [fasting plasma glucose (mmol/L) - 3.5]
    Change From Baseline in HOMA-%β at Week 26
    HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = [20 x fasting insulin (μU/mL)] / [fasting plasma glucose (mmol/L) - 3.5]. Data presented exclude data following the initiation of rescue therapy.
    Change From Baseline in HOMA-%β at Week 52
    HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = [20 x fasting insulin (μU/mL)] / [fasting plasma glucose (mmol/L) - 3.5]. Data presented exclude data following the initiation of rescue therapy.
    Baseline EQ-5D 3-level Version (EQ-5D-3L) Questionnaire Score
    The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 1-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ visual analogue score (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best).
    Change From Baseline in EQ-5D-3L Questionnaire Score at Week 26
    The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 3-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ VAS that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best). Data presented exclude data following the initiation of rescue therapy.
    Change From Baseline in EQ-5D-3L Score at Week 52
    The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 3-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ VAS that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best). Data presented exclude data following the initiation of rescue therapy.

    Full Information

    First Posted
    January 13, 2014
    Last Updated
    August 15, 2018
    Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    Pfizer
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02036515
    Brief Title
    Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2)
    Official Title
    A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial to Evaluate the Safety and Efficacy of Ertugliflozin (MK-8835/PF-04971729) in the Treatment of Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    March 12, 2014 (Actual)
    Primary Completion Date
    June 6, 2016 (Actual)
    Study Completion Date
    June 6, 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    Pfizer

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a safety and efficacy study of ertugliflozin (MK-8835/PF-04971729) in the treatment of participants with type 2 diabetes mellitus who have inadequate glycemic control on metformin and sitagliptin. The primary objective of the trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared with the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.
    Detailed Description
    The duration of the trial will be approximately 69 weeks. This will include a 1-week Screening Period, an up to 12-week wash-off/titration /dose-stabilization period, a 2-week single-blind, placebo run-in period, a 52-week double-blind, placebo-controlled treatment period (including a 26-week Phase A and 26-week Phase B), and a post-treatment telephone contact 14 days after the last dose of blinded investigational product.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 2 Diabetes Mellitus

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    464 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ertugliflozin 5 mg
    Arm Type
    Experimental
    Arm Description
    Ertugliflozin, 5 mg, oral, once daily for 52 weeks
    Arm Title
    Ertugliflozin 15 mg
    Arm Type
    Experimental
    Arm Description
    Ertugliflozin, 15 mg, oral, once daily for 52 weeks
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Matching placebo to ertuglifozin, oral, once daily for 52 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Ertugliflozin 5 mg
    Other Intervention Name(s)
    MK-8835, PF-04971729
    Intervention Description
    Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Ertugliflozin 15 mg
    Other Intervention Name(s)
    MK-8835, PF-04971729
    Intervention Description
    Ertugliflozin, oral, 5 mg and 10 mg tablet once daily for 52 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo for ertugliflozin 5 mg
    Intervention Description
    Matching placebo for ertugliflozin 5 mg, oral, once daily for 52 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Metformin
    Other Intervention Name(s)
    Glucophage, Glucophage XR
    Intervention Description
    Participants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period.
    Intervention Type
    Drug
    Intervention Name(s)
    Sitagliptin
    Other Intervention Name(s)
    JANUVIA®
    Intervention Description
    Participants are to remain on their stable doses of sitagliptin (oral, 100 mg once daily) while receiving blinded investigational product during the double-blind treatment period.
    Intervention Type
    Drug
    Intervention Name(s)
    Glimepiride
    Other Intervention Name(s)
    AMARYL
    Intervention Description
    Glimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion
    Intervention Type
    Biological
    Intervention Name(s)
    Insulin
    Intervention Description
    Insulin glargine rescue medication, injectable, as required. In the event that an investigator considers use of glimepiride to not be appropriate for a participant meeting protocol specified glycemic rescue criteria, insulin glargine can be initiated as the rescue medication, and managed by the investigator according to clinical practice guidelines of the local country.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo for ertugliflozin 10 mg
    Intervention Description
    Matching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks
    Primary Outcome Measure Information:
    Title
    Change From Baseline in Hemoglobin A1C at Week 26
    Description
    A1C is measured as percent. Thus this change from baseline reflects 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.
    Time Frame
    Baseline and Week 26
    Title
    Percentage of Participants Experiencing An Adverse Event (AE)
    Description
    An adverse event is defined as any untoward medical occurrence in a participant 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.
    Time Frame
    Up to Week 54
    Title
    Percentage of Participants Discontinuing Study Treatment Due to an AE
    Description
    An adverse event is defined as any untoward medical occurrence in a participant 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.
    Time Frame
    Up to Week 52
    Secondary Outcome Measure Information:
    Title
    Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
    Description
    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 rescue therapy.
    Time Frame
    Baseline and Week 26
    Title
    Change From Baseline in Body Weight at Week 26
    Description
    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.
    Time Frame
    Baseline and Week 26
    Title
    Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 26
    Description
    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.
    Time Frame
    Week 26
    Title
    Change From Baseline in Sitting Systolic Blood Pressure at Week 26
    Description
    The change from baseline is the Week 26 systolic blood pressure minus the Week 0 systolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 26
    Title
    Change From Baseline in Hemoglobin A1C at Week 52
    Description
    A1C is measured as percent. Thus this change from baseline reflects the Week 52 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.
    Time Frame
    Baseline and Week 52
    Title
    Change From Baseline in FPG at Week 52
    Description
    The change from baseline is the Week 52 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 rescue therapy.
    Time Frame
    Baseline and Week 52
    Title
    Change From Baseline in Body Weight at Week 52
    Description
    The change from baseline is the Week 52 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 52
    Title
    Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 52
    Description
    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.
    Time Frame
    Week 52
    Title
    Change From Baseline in Sitting Systolic Blood Pressure at Week 52
    Description
    The change from baseline is the Week 52 systolic blood pressure minus the Week 0 systolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 52
    Title
    Change From Baseline in Sitting Diastolic Blood Pressure at Week 26
    Description
    The change from baseline is the Week 26 diastolic blood pressure minus the Week 0 diastolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 26
    Title
    Change From Baseline in Sitting Diastolic Blood Pressure at Week 52
    Description
    The change from baseline is the Week 52 diastolic blood pressure minus the Week 0 diastolic blood pressure. Sitting blood pressure was measured in triplicate. Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 52
    Title
    Percentage of Participants Receiving Glycemic Rescue Medication by Week 26
    Description
    Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant).
    Time Frame
    Week 26
    Title
    Percentage of Participants Receiving Glycemic Rescue Medication by Week 52
    Description
    Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant).
    Time Frame
    Week 52
    Title
    Time to Initiation of Glycemic Rescue by Week 26
    Description
    Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant). Data presented are the minimum and maximum times to the initiation of rescue therapy in days. Below data include data from 1 participant in the Placebo arm who continued Phase A treatment for an additional 30 days.
    Time Frame
    Up to Week 26 (plus 30 days for 1 placebo participant)
    Title
    Time to Initiation of Glycemic Rescue by Week 52
    Description
    Glycemic rescue medication was initiated for participants who met progressively more stringent glycemic rescue criteria. Rescue medication included glimepiride (or insulin glargine if glimepiride was not considered appropriate for the participant). Data presented are the minimum and maximum times to the initiation of rescue therapy in days.
    Time Frame
    Up to week 52
    Title
    Baseline Homeostasis Model Assessment of β-cell Function (HOMA-%β) Value
    Description
    HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = [20 x fasting insulin (μU/mL)] / [fasting plasma glucose (mmol/L) - 3.5]
    Time Frame
    Baseline
    Title
    Change From Baseline in HOMA-%β at Week 26
    Description
    HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = [20 x fasting insulin (μU/mL)] / [fasting plasma glucose (mmol/L) - 3.5]. Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 26
    Title
    Change From Baseline in HOMA-%β at Week 52
    Description
    HOMA-%β is a well-accepted means of assessing fasting β-cell function, and is calculated using measured C-peptide and glucose levels and is measured as a percentage of a normal reference population. HOMA-%β = [20 x fasting insulin (μU/mL)] / [fasting plasma glucose (mmol/L) - 3.5]. Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 52
    Title
    Baseline EQ-5D 3-level Version (EQ-5D-3L) Questionnaire Score
    Description
    The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 1-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ visual analogue score (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best).
    Time Frame
    Baseline
    Title
    Change From Baseline in EQ-5D-3L Questionnaire Score at Week 26
    Description
    The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 3-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ VAS that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best). Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 26
    Title
    Change From Baseline in EQ-5D-3L Score at Week 52
    Description
    The EQ-5D-3L is a health profile questionnaire that assesses quality of life along 5 dimensions. Participants rate 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 3-15 with "3" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also includes an EQ VAS that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best). Data presented exclude data following the initiation of rescue therapy.
    Time Frame
    Baseline and Week 52

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosis of type 2 diabetes mellitus (T2DM) On stable diabetes therapy of metformin with either sitagliptin or another dipeptidyl peptidase-4 (DPP-4) inhibitor or a sulfonylurea (SU) prior to study participation and is willing to wash-off/switch from another DPP-4 inhibitor/SU to sitagliptin Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2 Male, postmenopausal female or surgically sterile female If a female of reproductive potential, agrees to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug Exclusion Criteria: History of type 1 diabetes mellitus or a history of ketoacidosis History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrine disorders, drug- or chemical-induced, and post-organ transplant) A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) or DPP-4 inhibitor On a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable Has undergone bariatric surgery within the past 12 months or >12 months and is not weight stable Has been treated with insulin (except for short-term use [<= 7 days]), injectable antihyperglycemic agents (AHAs) (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other sodium-glucose co-transporter 2 (SGLT2) inhibitors, alpha glucosidase inhibitors or meglitinides, bromocriptine (Cycloset™), colesevelam (Welchol™), or any other non-protocol approved AHAs within 12 weeks of study participation Has active, obstructive uropathy or indwelling urinary catheter 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 history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer Known history of Human Immunodeficiency Virus (HIV) Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or any other clinically significant hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) A medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease Has any clinically significant malabsorption condition If taking thyroid replacement therapy, has not been on a stable dose for at least 6 weeks prior to study participation Has been previously randomized in a study with ertugliflozin Has participated in other studies involving an investigational drug within 30 days prior or during study participation Has undergone a surgical procedure within 6 weeks prior to or planned major surgery during study participation Has a positive urine pregnancy test Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of study medication Planning to undergo hormonal therapy in preparation to donate eggs during the trial, including 14 days following the last dose of study medication Excessive consumption of alcoholic beverages or binge drinking Has donated blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    28921862
    Citation
    Dagogo-Jack S, Liu J, Eldor R, Amorin G, Johnson J, Hille D, Liao Y, Huyck S, Golm G, Terra SG, Mancuso JP, Engel SS, Lauring B. Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study. Diabetes Obes Metab. 2018 Mar;20(3):530-540. doi: 10.1111/dom.13116. Epub 2017 Oct 23.
    Results Reference
    result
    PubMed Identifier
    32700393
    Citation
    Gallo S, Raji A, Calle RA, Pong A, Meyer C. The effects of ertugliflozin on beta-cell function: Pooled analysis from four phase 3 randomized controlled studies. Diabetes Obes Metab. 2020 Dec;22(12):2267-2275. doi: 10.1111/dom.14149. Epub 2020 Aug 27.
    Results Reference
    derived
    PubMed Identifier
    32648108
    Citation
    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.
    Results Reference
    derived
    PubMed Identifier
    32372382
    Citation
    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.
    Results Reference
    derived
    PubMed Identifier
    32324082
    Citation
    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.
    Results Reference
    derived
    PubMed Identifier
    32324065
    Citation
    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.
    Results Reference
    derived
    PubMed Identifier
    31797522
    Citation
    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.
    Results Reference
    derived
    PubMed Identifier
    31064361
    Citation
    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.
    Results Reference
    derived

    Learn more about this trial

    Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006; VERTIS SITA2)

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