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

NCT02099110 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 8835-005MK-8835-005B15210192013-003698-82
• Study Type: interventional
• Target: 1,233
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline and Week 26

• 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.

  Up to 54 weeks

• 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.

  Up to 52 weeks

Secondary Outcomes (5)

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

  Baseline and Week 26

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

  Baseline and Week 26

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

  Week 26

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

  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

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

  Baseline and Week 26

Study Arms (5)

Ertugliflozin 5 mg + sitagliptin 100 mg

EXPERIMENTAL

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

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 mg

EXPERIMENTAL

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

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 mg

EXPERIMENTAL

Ertugliflozin 5 mg, oral, once daily for 52 weeks

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 mg

EXPERIMENTAL

Ertugliflozin, oral, once daily for 52 weeks

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 mg

ACTIVE COMPARATOR

Sitagliptin 100 mg, oral, once daily for 52 weeks

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

Interventions

Matching Placebo to Ertugliflozin 5 mg DRUG

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

Sitagliptin 100 mg

Matching Placebo to Ertugliflozin 10 mg DRUG

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

Ertugliflozin 5 mg; Ertugliflozin 5 mg + sitagliptin 100 mg; Sitagliptin 100 mg

Matching Placebo to sitagliptin 100 mg DRUG

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

Ertugliflozin 15 mg; Ertugliflozin 5 mg

Ertugliflozin 5 mg DRUG

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

Also known as: MK-8835, PF-04971729

Ertugliflozin 15 mg; Ertugliflozin 15 mg + sitagliptin 100 mg; Ertugliflozin 5 mg; Ertugliflozin 5 mg + sitagliptin 100 mg

Ertugliflozin 10 mg DRUG

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

Also known as: MK-8835, PF-04971729

Ertugliflozin 15 mg; Ertugliflozin 15 mg + sitagliptin 100 mg

Sitagliptin 100 mg DRUG

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

Also known as: JANUVIA®

Ertugliflozin 15 mg + sitagliptin 100 mg; Ertugliflozin 5 mg + sitagliptin 100 mg; Sitagliptin 100 mg

Metformin >= 1500 mg/day DRUG

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

Also known as: Glucophage, Glucophage XR

Ertugliflozin 15 mg; Ertugliflozin 15 mg + sitagliptin 100 mg; Ertugliflozin 5 mg; Ertugliflozin 5 mg + sitagliptin 100 mg; Sitagliptin 100 mg

Insulin Glargine Rescue Medication BIOLOGICAL

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

Also known as: Lantus

Ertugliflozin 15 mg; Ertugliflozin 15 mg + sitagliptin 100 mg; Ertugliflozin 5 mg; Ertugliflozin 5 mg + sitagliptin 100 mg; Sitagliptin 100 mg

Glimepiride Rescue Medication DRUG

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

Also known as: AMARYL

Ertugliflozin 15 mg; Ertugliflozin 15 mg + sitagliptin 100 mg; Ertugliflozin 5 mg; Ertugliflozin 5 mg + sitagliptin 100 mg; Sitagliptin 100 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Pfizer: collaborator

Related Publications (8)

• 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.

  PMID: 29266675 RESULT

• 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.

  PMID: 34213819 DERIVED

• 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.

  PMID: 32700393 DERIVED

• 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.

  PMID: 32648108 DERIVED

• 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.

  PMID: 32372382 DERIVED

• 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.

  PMID: 32324082 DERIVED

• 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.

  PMID: 32324065 DERIVED

• 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.

  PMID: 31797522 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin; Sitagliptin Phosphate; Metformin; Insulin Glargine; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Biguanides; Guanidines; Amidines; Organic Chemicals; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2014
• First Posted: March 28, 2014
• Study Start: April 22, 2014
• Primary Completion: May 26, 2016
• Study Completion: May 26, 2016
• Last Updated: September 12, 2018
• Results First Posted: November 1, 2017

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share