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

NCT ID: NCT02099110

Last Updated: 2018-09-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1233 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-22

Study Completion Date

2016-05-26

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Ertugliflozin 5 mg + sitagliptin 100 mg

Ertugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks

Group Type EXPERIMENTAL

Matching Placebo to Ertugliflozin 10 mg

Intervention Type DRUG

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

Ertugliflozin 5 mg

Intervention Type DRUG

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

Sitagliptin 100 mg

Intervention Type DRUG

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

Metformin >= 1500 mg/day

Intervention Type DRUG

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

Insulin Glargine Rescue Medication

Intervention Type BIOLOGICAL

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

Glimepiride Rescue Medication

Intervention Type DRUG

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

Ertugliflozin 15 mg + sitagliptin 100 mg

Ertugliflozin 15 mg + sitagliptin 100 mg, oral, once daily for 52 weeks

Group Type EXPERIMENTAL

Ertugliflozin 5 mg

Intervention Type DRUG

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

Ertugliflozin 10 mg

Intervention Type DRUG

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

Sitagliptin 100 mg

Intervention Type DRUG

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

Metformin >= 1500 mg/day

Intervention Type DRUG

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

Insulin Glargine Rescue Medication

Intervention Type BIOLOGICAL

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

Glimepiride Rescue Medication

Intervention Type DRUG

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

Ertugliflozin 5 mg

Ertugliflozin 5 mg, oral, once daily for 52 weeks

Group Type EXPERIMENTAL

Matching Placebo to Ertugliflozin 10 mg

Intervention Type DRUG

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

Matching Placebo to sitagliptin 100 mg

Intervention Type DRUG

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

Ertugliflozin 5 mg

Intervention Type DRUG

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

Metformin >= 1500 mg/day

Intervention Type DRUG

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

Insulin Glargine Rescue Medication

Intervention Type BIOLOGICAL

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

Glimepiride Rescue Medication

Intervention Type DRUG

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

Ertugliflozin 15 mg

Ertugliflozin, oral, once daily for 52 weeks

Group Type EXPERIMENTAL

Matching Placebo to sitagliptin 100 mg

Intervention Type DRUG

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

Ertugliflozin 5 mg

Intervention Type DRUG

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

Ertugliflozin 10 mg

Intervention Type DRUG

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

Metformin >= 1500 mg/day

Intervention Type DRUG

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

Insulin Glargine Rescue Medication

Intervention Type BIOLOGICAL

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

Glimepiride Rescue Medication

Intervention Type DRUG

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

Sitagliptin 100 mg

Sitagliptin 100 mg, oral, once daily for 52 weeks

Group Type ACTIVE_COMPARATOR

Matching Placebo to Ertugliflozin 5 mg

Intervention Type DRUG

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

Matching Placebo to Ertugliflozin 10 mg

Intervention Type DRUG

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

Sitagliptin 100 mg

Intervention Type DRUG

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

Metformin >= 1500 mg/day

Intervention Type DRUG

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

Insulin Glargine Rescue Medication

Intervention Type BIOLOGICAL

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

Glimepiride Rescue Medication

Intervention Type DRUG

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

Interventions

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Matching Placebo to Ertugliflozin 5 mg

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

Intervention Type DRUG

Matching Placebo to Ertugliflozin 10 mg

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

Intervention Type DRUG

Matching Placebo to sitagliptin 100 mg

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

Intervention Type DRUG

Ertugliflozin 5 mg

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

Intervention Type DRUG

Ertugliflozin 10 mg

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

Intervention Type DRUG

Sitagliptin 100 mg

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

Intervention Type DRUG

Metformin >= 1500 mg/day

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

Intervention Type DRUG

Insulin Glargine Rescue Medication

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

Intervention Type BIOLOGICAL

Glimepiride Rescue Medication

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

Intervention Type DRUG

Other Intervention Names

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MK-8835 PF-04971729 MK-8835 PF-04971729 JANUVIA® Glucophage Glucophage XR Lantus AMARYL

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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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.

Reference Type RESULT
PMID: 29266675 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34213819 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32700393 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32648108 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32372382 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32324082 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32324065 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31797522 (View on PubMed)

Other Identifiers

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MK-8835-005

Identifier Type: OTHER

Identifier Source: secondary_id

B1521019

Identifier Type: OTHER

Identifier Source: secondary_id

2013-003698-82

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8835-005

Identifier Type: -

Identifier Source: org_study_id

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