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)

NCT02036515 | Completed Phase 3 Results DMC

• 3 other identifiers: 8835-0062013-003697-26B1521015
• Study Type: interventional
• Target: 464
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to Week 52

Secondary Outcomes (21)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

  Baseline and Week 26

• Change From Baseline in Body Weight at Week 26

  Baseline and Week 26

• Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 26

  Week 26

• Change From Baseline in Sitting Systolic Blood Pressure at Week 26

  Baseline and Week 26

• Change From Baseline in Hemoglobin A1C at Week 52

  Baseline and Week 52

Study Arms (3)

Ertugliflozin 5 mg

EXPERIMENTAL

Ertugliflozin, 5 mg, oral, once daily for 52 weeks

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

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

Drug: Placebo for ertugliflozin 5 mg; Drug: Metformin; Drug: Sitagliptin; Drug: Glimepiride; Biological: Insulin; Drug: Placebo for ertugliflozin 10 mg

Interventions

Ertugliflozin 5 mg DRUG

Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks

Also known as: MK-8835, PF-04971729

Ertugliflozin 5 mg

Ertugliflozin 15 mg DRUG

Ertugliflozin, oral, 5 mg and 10 mg tablet once daily for 52 weeks

Also known as: MK-8835, PF-04971729

Ertugliflozin 15 mg

Placebo for ertugliflozin 5 mg DRUG

Matching placebo for ertugliflozin 5 mg, oral, once daily for 52 weeks

Placebo

Metformin DRUG

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.

Also known as: Glucophage, Glucophage XR

Ertugliflozin 15 mg; Ertugliflozin 5 mg; Placebo

Sitagliptin DRUG

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.

Also known as: JANUVIA®

Ertugliflozin 15 mg; Ertugliflozin 5 mg; Placebo

Glimepiride DRUG

Glimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion

Also known as: AMARYL

Ertugliflozin 15 mg; Ertugliflozin 5 mg; Placebo

Insulin BIOLOGICAL

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.

Ertugliflozin 15 mg; Ertugliflozin 5 mg; Placebo

Placebo for ertugliflozin 10 mg DRUG

Matching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks

Ertugliflozin 5 mg; Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

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

Related Publications (8)

• 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.

  PMID: 28921862 RESULT

• 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

• Liu 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.

  PMID: 31064361 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin; Metformin; Sitagliptin Phosphate; glimepiride; Insulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Proinsulin; 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: January 13, 2014
• First Posted: January 15, 2014
• Study Start: March 12, 2014
• Primary Completion: June 6, 2016
• Study Completion: June 6, 2016
• Last Updated: September 13, 2018
• Results First Posted: July 24, 2017

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share