A Study to Evaluate the Efficacy and Safety of Ertugliflozin in Asian Participants With Type 2 Diabetes and Inadequate Glycemic Control on Metformin Monotherapy (MK-8835-012)

NCT02630706

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Type 2 Diabetes Mellitus
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Asian participants ≥18 years of age at the time of initial Screening.

- Type 2 diabetes mellitus as per American Diabetes Association guidelines.

- Metformin monotherapy (≥1500 mg/day) with an initial Screening A1C of 7.0-10.5% (53-91 mmol/mol) OR metformin monotherapy (<1500 mg/day) with an initial Screening A1C of 7.5-11.0% (58-97 mmol/mol) OR dual combination therapy with metformin + sulfonylurea, dipeptidyl peptidase-4 (DDP-4) inhibitor, meglitinide, or alpha-glucosidase inhibitor with an initial Screening A1C of 6.5-9.5% (48-80 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.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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 endocrinopathies, drug- or chemical-induced, and
post-organ transplant.)


- 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.


- Mean value for triplicate screening sitting systolic blood pressure >160 mm Hg and/or
diastolic blood pressure >90 mm Hg after at least a 5-minute seated rest at screening


- 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.


- Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or
engages in binge drinking.


- Any clinically significant malabsorption condition.


- 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.


- A known hypersensitivity or intolerance to any sodium glucose co-transporter (SGLT2)
inhibitor.


- On a previous clinical study with ertugliflozin.


- Is taking blood pressure or lipid altering medications that have not been on a stable
dose for at least 4 weeks prior to study start.


- Current treatment for hyperthyroidism.


- Male participants with a serum creatinine >=1.3 mg/dL (>=115 mol/L) or female
participants with a serum creatinine >=1.2 mg/dL (>=106 mol/L) or participants with an
estimated glomerular filtration rate (eGFR) <55 mL/min/1.73m^2 according to the
4-variable Modification of Diet in Renal Disease (MDRD) equation at screening.


- An aspartate transaminase (AST) or alanine transaminase (ALT) >2X the upper limit of
normal (ULN) range at screening, or a total bilirubin >1.5 X the ULN unless the
participant has a history of Gilbert's.


- On thyroid replacement therapy and has not been on a stable dose for at least 6 weeks
prior to study start.


- 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.


- 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
during concomitant illness or other stress), other injectable anti-hyperglycemic
agents (e.g., pramlintide, exenatide, liraglutide), another SGLT2 inhibitor,
bromocriptine, colesevelam, rosiglitazone or pioglitazone, or any other AHA with the
exception of the protocol-approved agents.


- Is on or likely to require treatment ≥14 consecutive days or repeated courses of
pharmacologic doses of corticosteroids.


- Has undergone a surgical procedure within 6 weeks prior to study start or has planned
major surgery during the study.


- 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.


- Donated blood or blood products within 6 weeks of study start.


- Has Human Immunodeficiency Virus (HIV).


- Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells.


- Has clinically important hematological disorders (such as aplastic anemia,
myeloproliferative or myelodyplastic syndromes, thrombocytopenia.)

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Advanced Information
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy and Safety of Ertugliflozin in Asian Participants With Type 2 Diabetes and Inadequate Glycemic Control on Metformin Monotherapy (MK-8835-012)
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 26-Week Multicenter Study to Evaluate the Efficacy and Safety of Ertugliflozin in Asian Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control on Metformin Monotherapy (VERTIS-ASIA)
Brief Summary This is a study to evaluate the efficacy and safety of the addition of ertugliflozin to metformin monotherapy in Asian participants with Type 2 diabetes mellitis (T2DM) who have inadequate glycemic control on metformin monotherapy. The primary hypothesis is that the mean reduction from baseline in HbA1C for 15 mg and 5 mg ertugliflozin (tested sequentially) is greater than for placebo.
Detailed Description This study includes a 1-week screening period, an 8-week (or greater) antihyperglycemic agent (AHA) wash-off and/or metformin dose stable period (as necessary), a 2-week single-blind placebo run-in period, a 26-week double-blind treatment period, and a post-treatment telephone contact 14 days after the last dose of study drug.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:
Sponsor was masked.
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Ertugliflozin 5 mg
    Ertugliflozin 5 mg oral tablet taken once daily
    Other Names:
    • MK-8835
    • PF-04971729
  • Drug: Ertugliflozin 15 mg
    Ertugliflozin 15 mg (5-mg and 10-mg tablets) oral taken once daily
    Other Names:
    • MK-8835
    • PF-04971729
  • Drug: Placebo matching ertugliflozin
    Placebo matching ertugliflozin (5-mg and/or 10-mg tablet) oral taken once daily
  • Drug: Metformin
    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. Participants on metformin <1500 at screening are up-titrated to >= 1500 daily.
  • Drug: Glimepiride
    Glycemic rescue therapy with open-label glimepiride will be initiated in participants with glucose values exceeding protocol-specified values. Dosing and titration of open-label glimepiride rescue therapy will be at the Investigator's discretion.
Study Arms  ICMJE
  • Experimental: Ertugliflozin 5 mg
    Ertugliflozin 5 mg oral and matching placebo for ertugliflozin 10 mg, oral, once daily for 26 weeks, while maintaining metformin at a stable dose (>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
    Interventions:
    • Drug: Ertugliflozin 5 mg
    • Drug: Placebo matching ertugliflozin
    • Drug: Metformin
    • Drug: Glimepiride
  • Experimental: Ertugliflozin 15 mg
    Ertugliflozin 15 mg (ertugliflozin 5 mg + ertugliflozin 10 mg) administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
    Interventions:
    • Drug: Ertugliflozin 15 mg
    • Drug: Metformin
    • Drug: Glimepiride
  • Placebo Comparator: Placebo
    Placebo matching ertugliflozin administered orally once daily for 26 weeks, while maintaining metformin at a stable dose (>=1500 mg/day). Glycemic rescue therapy with open-label glimepiride was initiated in participants with glucose values exceeding protocol-specified values.
    Interventions:
    • Drug: Placebo matching ertugliflozin
    • Drug: Metformin
    • Drug: Glimepiride
Publications * Ji L, Liu Y, Miao H, Xie Y, Yang M, Wang W, Mu Y, Yan P, Pan S, Lauring B, Liu S, Huyck S, Qiu Y, Terra SG. Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia. Diabetes Obes Metab. 2019 Jun;21(6):1474-1482. doi: 10.1111/dom.13681. Epub 2019 Apr 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 9, 2018)
506
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2015)
495
Actual Study Completion Date  ICMJE December 27, 2017
Actual Primary Completion Date December 27, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Asian participants ?18 years of age at the time of initial Screening.
  • Type 2 diabetes mellitus as per American Diabetes Association guidelines.
  • Metformin monotherapy (?1500 mg/day) with an initial Screening A1C of 7.0-10.5% (53-91 mmol/mol) OR metformin monotherapy (<1500 mg/day) with an initial Screening A1C of 7.5-11.0% (58-97 mmol/mol) OR dual combination therapy with metformin + sulfonylurea, dipeptidyl peptidase-4 (DDP-4) inhibitor, meglitinide, or alpha-glucosidase inhibitor with an initial Screening A1C of 6.5-9.5% (48-80 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.

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 endocrinopathies, drug- or chemical-induced, and post-organ transplant.)
  • 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.
  • Mean value for triplicate screening sitting systolic blood pressure >160 mm Hg and/or diastolic blood pressure >90 mm Hg after at least a 5-minute seated rest at screening
  • 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.
  • Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or engages in binge drinking.
  • Any clinically significant malabsorption condition.
  • 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.
  • A known hypersensitivity or intolerance to any sodium glucose co-transporter (SGLT2) inhibitor.
  • On a previous clinical study with ertugliflozin.
  • Is taking blood pressure or lipid altering medications that have not been on a stable dose for at least 4 weeks prior to study start.
  • Current treatment for hyperthyroidism.
  • Male participants with a serum creatinine >=1.3 mg/dL (>=115 mol/L) or female participants with a serum creatinine >=1.2 mg/dL (>=106 mol/L) or participants with an estimated glomerular filtration rate (eGFR) <55 mL/min/1.73m^2 according to the 4-variable Modification of Diet in Renal Disease (MDRD) equation at screening.
  • An aspartate transaminase (AST) or alanine transaminase (ALT) >2X the upper limit of normal (ULN) range at screening, or a total bilirubin >1.5 X the ULN unless the participant has a history of Gilbert's.
  • On thyroid replacement therapy and has not been on a stable dose for at least 6 weeks prior to study start.
  • 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.
  • 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 during concomitant illness or other stress), other injectable anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), another SGLT2 inhibitor, bromocriptine, colesevelam, rosiglitazone or pioglitazone, or any other AHA with the exception of the protocol-approved agents.
  • Is on or likely to require treatment ?14 consecutive days or repeated courses of pharmacologic doses of corticosteroids.
  • Has undergone a surgical procedure within 6 weeks prior to study start or has planned major surgery during the study.
  • 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.
  • Donated blood or blood products within 6 weeks of study start.
  • Has Human Immunodeficiency Virus (HIV).
  • Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells.
  • Has clinically important hematological disorders (such as aplastic anemia, myeloproliferative or myelodyplastic syndromes, thrombocytopenia.)
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries China,   Hong Kong,   Korea, Republic of,   Philippines,   Taiwan
 
Administrative Information
NCT Number  ICMJE NCT02630706
Other Study ID Numbers  ICMJE 8835-012
B1521045 ( Other Identifier: Pfizer Protocol Number )
MK-8835-012 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialD…
URL:http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director:Medical DirectorMerck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date November 2018

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