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Type 2 Diabetes MellitusPhase 3NCT02099110

Ertugliflozin and Sitagliptin Co-administration Factorial Study (VERTIS FACTORAL, MK-8835-005)

A Phase 3 study testing Ertugliflozin 5 mg and Ertugliflozin 10 mg in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a study of co-administration of ertugliflozin (MK-8835/PF-04971729) and sitagliptin given together or alone along with metformin in participants with Type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin monotherapy. 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 and Ertugliflozin 10 mg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,233 participants
Where
No sites listed yet
Study dates
22 Apr 2014to 26 May 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

  • Type 2 diabetes mellitus as per American Diabetes Association guidelines
  • On metformin monotherapy (>=1500 mg/day) for >=8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy (>=1500 mg/day) for <8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy <1500 mg/day with a Visit 1/Screening A1C >=8.0% and <=11.5% (>=64 mmol/mol and <=102 mmol/mol)
  • Body mass index (BMI) >=18.0 kg/m^2
  • Male or female not of reproductive potential
  • Female of reproductive potential who agrees to remain abstinent from heterosexual activity or to use 2 acceptable combinations of contraception

Who cannot join

  • History of type 1 diabetes mellitus or ketoacidosis
  • History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant
  • A known hypersensitivity or intolerance to any sodium glucose co-transporter 2 (SGLT2) inhibitor or sitagliptin
  • Has been treated with any of the following agents within 12 weeks of study start or during the pre-randomization period: Insulin of any type (except for short-term use [i.e., <=7 days] during concomitant illness or other stress), other injectable anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other SGLT2 inhibitors, alpha glucosidase inhibitors or meglitinides, dipeptidyl-peptidase 4 inhibitor (DPP-4 inhibitor), sulfonylureas (SUs), bromocriptine (Cycloset™), colesevelam (Welchol™), any other antihyperglycemic agents (AHA) with the exception of the protocol-approved agents
  • Is on a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable prior to study start
  • Has undergone bariatric surgery within the past 12 months or >12 months and is not weight stable prior to study start
Show all 27Show fewer
  • A 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 start
  • Active, obstructive uropathy or indwelling urinary catheter
  • History of malignancy <=5 years prior to study start, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
  • A known history of human immunodeficiency virus (HIV)
  • A blood dyscrasia or any disorder causing hemolysis or unstable red blood cells, or a clinically important hematological disorder (e.g. aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
  • A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
  • Any clinically significant malabsorption condition
  • Current treatment for hyperthyroidism
  • On thyroid replacement therapy and not on a stable dose for at least 6 weeks prior study start
  • On a previous clinical study with ertugliflozin
  • Estimated glomerular filtration rate (eGFR) (using the 4-variable Modification of Diet in Renal Disease Study Equation (MDRD) equation) <60 mL/min/1.73 m^2
  • Serum creatinine >= 1.3 mg/dL (115 µmol/L) for males and >= 1.2 mg/dL (106 µmol/L) for females
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times upper limit of normal
  • Hemoglobin <12 g/dL (120 g/L) for males and <11 g/dL (110 g/L) for females.
  • Participated in other studies involving investigational drug(s) 30 days prior to study start
  • Surgical procedure within 6 weeks prior to study start or major surgery planned during the trial
  • Positive urine pregnancy test
  • Pregnant or breast-feeding, or planning to conceive during the trial, including 14 days following the last dose of study medication
  • Planning to undergo hormonal therapy in preparation for egg donation during the trial, including 14 days following the last dose of study medication
  • Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or engages in binge drinking
  • Donated blood or blood products within 6 weeks of study start

About this study

Official title: A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin Compared With Ertugliflozin Alone and Sitagliptin Alone, in the Treatment of Subjects With T2DM With Inadequate Glycemic Control on Metformin Monotherapy

This is a study of co-administration of ertugliflozin (MK-8835/PF-04971729) and sitagliptin given together or alone along with metformin in participants with Type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin monotherapy. The primary hypothesis of this study is that ertugliflozin 15 mg daily plus sitagliptin 100 mg daily provides greater hemoglobin A1C (A1C)-lowering compared with sitagliptin 100 mg daily alone.

Read the detailed description

This study will include a 1-week screening period; an up to 12-week metformin titration/dose stabilization period; a 2-week single-blind placebo run-in period; a 52-week (26-week Phase A and 26-week Phase B) double-blind treatment period and a post-treatment telephone contact 14 days after the last dose of study medication.

Being tested
Matching Placebo to Ertugliflozin 5 mg, Matching Placebo to Ertugliflozin 10 mg, Matching Placebo to sitagliptin 100 mg, Ertugliflozin 5 mg, Ertugliflozin 10 mg
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.

  • Matching Placebo to Ertugliflozin 5 mgDrug

    Placebo to ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period

  • Matching Placebo to Ertugliflozin 10 mgDrug

    Placebo to ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period

  • Matching Placebo to sitagliptin 100 mgDrug

    Placebo to sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period

  • Ertugliflozin 5 mgDrug

    Also called MK-8835, PF-04971729

    Ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period

  • Ertugliflozin 10 mgDrug

    Also called MK-8835, PF-04971729

    Ertugliflozin 10 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period

  • Sitagliptin 100 mgDrug

    Also called JANUVIA®

    Sitagliptin 100 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period

  • Metformin >= 1500 mg/dayDrug

    Also called Glucophage, Glucophage XR

    Metformin >= 1500 mg/day, tablets, oral, for 52 weeks while receiving blinded investigational product during the double-blind treatment period

  • Insulin Glargine Rescue MedicationBiological

    Also called Lantus

    Open-label insulin glargine, subcutaneous injection, as required as a rescue medication; dose determined per the investigator's discretion

  • Glimepiride Rescue MedicationDrug

    Also called AMARYL

    Open-label glimepiride tablets, oral, as required as a rescue medication, dose determined per the investigator's discretion

Study groups in NCT02099110
Study groupRoleWhat they receive
Ertugliflozin 5 mg + sitagliptin 100 mgExperimentalErtugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks
Receives: Drug: Matching Placebo to Ertugliflozin 10 mg; Drug: Ertugliflozin 5 mg; Drug: Sitagliptin 100 mg; Drug: Metformin >= 1500 mg/day; Biological: Insulin Glargine Rescue Medication; Drug: Glimepiride Rescue Medication
Ertugliflozin 15 mg + sitagliptin 100 mgExperimentalErtugliflozin 15 mg + sitagliptin 100 mg, oral, once daily for 52 weeks
Receives: Drug: Ertugliflozin 5 mg; Drug: Ertugliflozin 10 mg; Drug: Sitagliptin 100 mg; Drug: Metformin >= 1500 mg/day; Biological: Insulin Glargine Rescue Medication; Drug: Glimepiride Rescue Medication
Ertugliflozin 5 mgExperimentalErtugliflozin 5 mg, oral, once daily for 52 weeks
Receives: Drug: Matching Placebo to Ertugliflozin 10 mg; Drug: Matching Placebo to sitagliptin 100 mg; Drug: Ertugliflozin 5 mg; Drug: Metformin >= 1500 mg/day; Biological: Insulin Glargine Rescue Medication; Drug: Glimepiride Rescue Medication
Ertugliflozin 15 mgExperimentalErtugliflozin, oral, once daily for 52 weeks
Receives: Drug: Matching Placebo to sitagliptin 100 mg; Drug: Ertugliflozin 5 mg; Drug: Ertugliflozin 10 mg; Drug: Metformin >= 1500 mg/day; Biological: Insulin Glargine Rescue Medication; Drug: Glimepiride Rescue Medication
Sitagliptin 100 mgActive comparatorSitagliptin 100 mg, oral, once daily for 52 weeks
Receives: Drug: Matching Placebo to Ertugliflozin 5 mg; Drug: Matching Placebo to Ertugliflozin 10 mg; Drug: Sitagliptin 100 mg; Drug: Metformin >= 1500 mg/day; Biological: Insulin Glargine Rescue Medication; Drug: Glimepiride Rescue Medication

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in A1C at Week 26: Excluding Rescue Approach

    A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 26

  2. Percentage of Participants Who Experienced an Adverse Event (AE): Including Rescue Approach

    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. Including rescue approach data analysis included data following the initiation of rescue therapy.

    Measured: Up to 54 weeks

  3. Percentage of Participants Who Discontinued Study Treatment Due to an AE: Including Rescue Approach

    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. Including rescue approach data analysis included data following the initiation of rescue therapy.

    Measured: Up to 52 weeks

Secondary outcomes (5)

  1. Change From Baseline in Body Weight at Week 26: Excluding Rescue Approach

    This change from baseline reflects the Week 26 body weight minus the Week 0 body weight. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 26

  2. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 - Excluding Rescue Approach

    Blood glucose was measured on a fasting basis after at least a 10-hour fast. This change from baseline reflects the Week 26 FPG minus the Week 0 FPG. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 26

  3. Percentage of Participants Achieving a Hemoglobin A1C of <7% (<53 mmol/Mol) (Raw Proportions): Excluding Rescue Approach

    A1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

    Measured: Week 26

  4. Change From Baseline in Static Beta-Cell Sensitivity to Glucose Index at Week 26; Excluding Rescue Approach

    Static beta-cell sensitivity to glucose index (SBCSGI) estimates the ratio of insulin secretion (expressed in pmol/min) related to above-basal glucose concentration (expressed in mmol/L * L) following a meal. Blood samples were collected before and after a standard meal and glucose, insulin, and C-peptide levels were analyzed. The C-peptides minimal model was used to estimate the insulin secretion rate (ISR). Analysis included both non-model-based [including insulinogenic index with C-peptide, glucose area under the curve (AUC)/insulin AUC] and model-based [beta cell function and insulin secretion rate at 9 mM glucose] testing. Analysis was performed with non-linear least squares using the Software Architecture Analysis Method (SAAM) II software. SBCSGI was expressed in units of 10^-9 min^-1. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

    Measured: 30 min. before and 0, 15, 30, 60, 90, 120, and 180 minutes following the start of the standard meal at Baseline and Week 26

  5. Change From Baseline in Sitting Systolic Blood Pressure at Week 26: Excluding Rescue Approach

    This change from baseline reflects the Week 26 systolic blood pressure minus the Week 0 systolic blood pressure. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

    Measured: Baseline and Week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2014 (estimated)
  2. Study start22 Apr 2014
  3. Primary completion26 May 2016
  4. Study completion26 May 2016

Resources

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
1,233 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02099110
Sponsor's protocol ID
8835-005
Other IDs
MK-8835-005, B1521019, 2013-003698-82
Status last verified
Aug 2018
First submitted
25 Mar 2014
Last updated
12 Sep 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Pratley RE, Eldor R, Raji A, Golm G, Huyck SB, Qiu Y, Sunga S, Johnson J, Terra SG, Mancuso JP, Engel SS, Lauring B. Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: The VERTIS FACTORIAL randomized trial. Diabetes Obes Metab. 2018 May;20(5):1111-1120. doi: 10.1111/dom.13194. Epub 2018 Jan 25.

    PubMed 29266675

  • 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.

    PubMed 34213819

  • 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.

    PubMed 32700393

  • 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.

    PubMed 32648108

  • 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.

    PubMed 32372382

  • 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.

    PubMed 32324082

  • 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.

    PubMed 32324065

  • 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.

    PubMed 31797522

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ertugliflozin 5 mg and Ertugliflozin 10 mg 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 27 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 12 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. 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 1 Nov 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 A1C at Week 26: Excluding Rescue Approach (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 NCT02099110, 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 12 Sep 2018.

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