Type 2 Diabetes MellitusPhase 3NCT02036515
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)
A Phase 3 study testing Ertugliflozin 5 mg, Ertugliflozin 15 mg and Metformin in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Ertugliflozin 5 mg, Ertugliflozin 15 mg and Metformin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 464 participants
- Where
- No sites listed yet
- Study dates
- 12 Mar 2014to 6 Jun 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
About this study
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
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.
Read the 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.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Ertugliflozin 5 mg, Ertugliflozin 15 mg, Placebo for ertugliflozin 5 mg, Metformin, Sitagliptin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ertugliflozin 5 mgDrug
Also called MK-8835, PF-04971729
Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks
Ertugliflozin 15 mgDrug
Also called MK-8835, PF-04971729
Ertugliflozin, oral, 5 mg and 10 mg tablet once daily for 52 weeks
Placebo for ertugliflozin 5 mgDrug
Matching placebo for ertugliflozin 5 mg, oral, once daily for 52 weeks
MetforminDrug
Also called Glucophage, Glucophage XR
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.
SitagliptinDrug
Also called JANUVIA®
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.
GlimepirideDrug
Also called AMARYL
Glimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion
InsulinBiological
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.
Placebo for ertugliflozin 10 mgDrug
Matching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ertugliflozin 5 mg | Experimental | Ertugliflozin, 5 mg, oral, once daily for 52 weeks Receives: Drug: Ertugliflozin 5 mg; Drug: Metformin; Drug: Sitagliptin; Drug: Glimepiride; Biological: Insulin; Drug: Placebo for ertugliflozin 10 mg |
| Ertugliflozin 15 mg | Experimental | Ertugliflozin, 15 mg, oral, once daily for 52 weeks Receives: Drug: Ertugliflozin 15 mg; Drug: Metformin; Drug: Sitagliptin; Drug: Glimepiride; Biological: Insulin |
| Placebo | Placebo comparator | Matching placebo to ertuglifozin, oral, once daily for 52 weeks Receives: Drug: Placebo for ertugliflozin 5 mg; Drug: Metformin; Drug: Sitagliptin; Drug: Glimepiride; Biological: Insulin; Drug: Placebo for ertugliflozin 10 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 26
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.
Measured: Up to Week 54
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.
Measured: Up to Week 52
Secondary outcomes (21)
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Week 26
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Week 52
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.
Measured: Baseline and Week 52
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 52
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).
Measured: Week 26
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).
Measured: Week 52
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.
Measured: Up to Week 26 (plus 30 days for 1 placebo participant)
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.
Measured: Up to week 52
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]
Measured: Baseline
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 52
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).
Measured: Baseline
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.
Measured: Baseline and Week 26
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.
Measured: Baseline and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2014 (estimated)
- Study start12 Mar 2014
- Primary completion6 Jun 2016
- Study completion6 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 464 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02036515
- Sponsor's protocol ID
- 8835-006
- Other IDs
- 2013-003697-26, B1521015
- Status last verified
- Aug 2018
- First submitted
- 13 Jan 2014
- Last updated
- 13 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 28921862Gallo 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.
PubMed 32700393Gallo 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.
PubMed 32648108Patel 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.
PubMed 32372382Liu 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.
PubMed 32324082Liu 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.
PubMed 32324065Liu 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.
PubMed 31797522Liu 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.
PubMed 31064361
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02036515
- Acronym / sponsor ID
- 8835-006
- Conditions
- Type 2 Diabetes Mellitus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 464 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Study start
- 12 Mar 2014 (actual)
- Primary completion
- 6 Jun 2016 (actual)
- Study completion
- 6 Jun 2016 (actual)
- First posted
- 15 Jan 2014 (estimated)
- Results
- Posted 24 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ertugliflozin 5 mg | Experimental | Drug: Ertugliflozin 5 mg, Drug: Metformin, Drug: Sitagliptin, Drug: Glimepiride, Biological: Insulin, Drug: Placebo for ertugliflozin 10 mgErtugliflozin, 5 mg, oral, once daily for 52 weeks |
| Ertugliflozin 15 mg | Experimental | Drug: Ertugliflozin 15 mg, Drug: Metformin, Drug: Sitagliptin, Drug: Glimepiride, Biological: InsulinErtugliflozin, 15 mg, oral, once daily for 52 weeks |
| Placebo | Placebo comparator | Drug: Placebo for ertugliflozin 5 mg, Drug: Metformin, Drug: Sitagliptin, Drug: Glimepiride, Biological: Insulin, Drug: Placebo for ertugliflozin 10 mgMatching placebo to ertuglifozin, oral, once daily for 52 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ertugliflozin 5 mgAlso: MK-8835, PF-04971729Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks | Drug | Ertugliflozin 5 mg |
| Ertugliflozin 15 mgAlso: MK-8835, PF-04971729Ertugliflozin, oral, 5 mg and 10 mg tablet once daily for 52 weeks | Drug | Ertugliflozin 15 mg |
| Placebo for ertugliflozin 5 mgMatching placebo for ertugliflozin 5 mg, oral, once daily for 52 weeks | Drug | Placebo |
| MetforminAlso: Glucophage, Glucophage XRParticipants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period. | Drug | Ertugliflozin 15 mg, Ertugliflozin 5 mg, Placebo |
| SitagliptinAlso: JANUVIA®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. | Drug | Ertugliflozin 15 mg, Ertugliflozin 5 mg, Placebo |
| GlimepirideAlso: AMARYLGlimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion | Drug | Ertugliflozin 15 mg, Ertugliflozin 5 mg, Placebo |
| InsulinInsulin 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. | Biological | Ertugliflozin 15 mg, Ertugliflozin 5 mg, Placebo |
| Placebo for ertugliflozin 10 mgMatching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks | Drug | Ertugliflozin 5 mg, Placebo |
Primary outcome
Change From Baseline in Hemoglobin A1C at Week 26
Time frame: Baseline and 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)
Time frame: Up to Week 54
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
Time frame: Up to Week 52
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.
21 secondary outcomes
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Time frame: Baseline and Week 26
Change From Baseline in Body Weight at Week 26
Time frame: Baseline and Week 26
Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 26
Time frame: Week 26
Change From Baseline in Sitting Systolic Blood Pressure at Week 26
Time frame: Baseline and Week 26
Change From Baseline in Hemoglobin A1C at Week 52
Time frame: Baseline and Week 52
Change From Baseline in FPG at Week 52
Time frame: Baseline and Week 52
Change From Baseline in Body Weight at Week 52
Time frame: Baseline and Week 52
Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 52
Time frame: Week 52
Change From Baseline in Sitting Systolic Blood Pressure at Week 52
Time frame: Baseline and Week 52
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26
Time frame: Baseline and Week 26
Change From Baseline in Sitting Diastolic Blood Pressure at Week 52
Time frame: Baseline and Week 52
Percentage of Participants Receiving Glycemic Rescue Medication by Week 26
Time frame: Week 26
Percentage of Participants Receiving Glycemic Rescue Medication by Week 52
Time frame: Week 52
Time to Initiation of Glycemic Rescue by Week 26
Time frame: Up to Week 26 (plus 30 days for 1 placebo participant)
Time to Initiation of Glycemic Rescue by Week 52
Time frame: Up to week 52
Baseline Homeostasis Model Assessment of β-cell Function (HOMA-%β) Value
Time frame: Baseline
Change From Baseline in HOMA-%β at Week 26
Time frame: Baseline and Week 26
Change From Baseline in HOMA-%β at Week 52
Time frame: Baseline and Week 52
Baseline EQ-5D 3-level Version (EQ-5D-3L) Questionnaire Score
Time frame: Baseline
Change From Baseline in EQ-5D-3L Questionnaire Score at Week 26
Time frame: Baseline and Week 26
Change From Baseline in EQ-5D-3L Score at Week 52
Time frame: Baseline and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28921862Dagogo-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.
- Derived from this study: PubMed 32700393Gallo 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.
- Derived from this study: PubMed 32648108Gallo 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.
- Derived from this study: PubMed 32372382Patel 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.
- Derived from this study: PubMed 32324082Liu 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.
- Derived from this study: PubMed 32324065Liu 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.
- Derived from this study: PubMed 31797522Liu 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.
- Derived from this study: PubMed 31064361Liu 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.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ertugliflozin 5 mg, Ertugliflozin 15 mg and Metformin in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Hemoglobin A1C at Week 26 (time frame: Baseline and Week 26). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02036515, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.