Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Diet and Exercise (MK-8835-017)

NCT02226003 | Completed Phase 3 Results DMC

• 3 other identifiers: 8835-0172014-001049-25B1521047
• Study Type: interventional
• Target: 291
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study to evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in combination with sitagliptin in the treatment of participants with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control on diet and exercise. The primary hypothesis of the study is that ertugliflozin plus sitagliptin is more effective in lowering of hemoglobin A1C (HbA1C) than placebo.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Hemoglobin A1C (HbA1C) at Week 26 - Full Analysis Set (FAS Population Excluding Rescue Approach

  HbA1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). HbA1C represents the percentage of glycated hemoglobin. A negative number indicates a reduction in HbA1C level. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.

  Baseline and Week 26

• Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants as Treated Excluding Rescue Approach

  An adverse event (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. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.

  Up to Week 28

• Percentage of Participants Who Discontinued Study Medication Due to an AE - All Participants as Treated Excluding 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. Excluding rescue approach excludes all data following the initiation of rescue, in order to avoid the confounding influence of the rescue therapy with open-label glimepiride.

  Up to Week 26

Secondary Outcomes (6)

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

  Baseline and Week 26

• Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 26 - Full Analysis Set Excluding Rescue Approach

  Baseline and Week 26

• Percentage of Participants With HbA1C <7% (<53 mmol/Mol) at Week 26

  Week 26

• Change From Baseline in Body Weight at Week 26 - Full Analysis Set Excluding Rescue Approach

  Baseline and Week 26

• Change From Baseline in Sitting Systolic Blood Pressure at Week 26 - Full Analysis Set Excluding Rescue Approach

  Baseline and Week 26

Study Arms (3)

Ertugliflozin 5 mg and Sitagliptin 100 mg

EXPERIMENTAL

Ertugliflozin, 5 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks. Placebo to ertugliflozin, 10 mg, administered orally, once daily for 26 weeks.

Drug: Ertugliflozin; Drug: Sitagliptin; Drug: Placebo to Ertugliflozin; Drug: Glimepiride

Ertugliflozin 15 mg and Sitagliptin 100 mg

EXPERIMENTAL

Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.

Drug: Ertugliflozin; Drug: Sitagliptin; Drug: Glimepiride

Placebo to Ertugliflozin and Placebo to Sitagliptin

PLACEBO COMPARATOR

Placebo to ertugliflozin, 5 mg and 10 mg, administered orally, once daily for 26 weeks. Placebo to sitagliptin, 100 mg, administered orally, once daily for 26 weeks.

Drug: Placebo to Ertugliflozin; Drug: Placebo to Sitagliptin; Drug: Glimepiride

Interventions

Ertugliflozin DRUG

Ertugliflozin, 5 mg or 15 mg, administered orally, once daily for 26 weeks.

Ertugliflozin 15 mg and Sitagliptin 100 mg; Ertugliflozin 5 mg and Sitagliptin 100 mg

Sitagliptin DRUG

Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.

Ertugliflozin 15 mg and Sitagliptin 100 mg; Ertugliflozin 5 mg and Sitagliptin 100 mg

Placebo to Ertugliflozin DRUG

Matching placebo to ertugliflozin administered orally, once daily for 26 weeks.

Ertugliflozin 5 mg and Sitagliptin 100 mg; Placebo to Ertugliflozin and Placebo to Sitagliptin

Placebo to Sitagliptin DRUG

Matching placebo to sitagliptin administered orally, once daily for 26 weeks.

Placebo to Ertugliflozin and Placebo to Sitagliptin

Glimepiride DRUG

Open-label glimepiride rescue therapy will be initiated at 1 or 2 mg/day and may be titrated to the maximum labeled dose or maximum tolerated dose (if lower than labeled dose), as considered appropriate by the investigator, based on blood glucose measurements and in accordance with the local, approved label.

Ertugliflozin 15 mg and Sitagliptin 100 mg; Ertugliflozin 5 mg and Sitagliptin 100 mg; Placebo to Ertugliflozin and Placebo to Sitagliptin

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
• Not on antihyperglycemic agent (AHA) \>=8 weeks with a Visit 1/Screening HbA1C \>=8.0% and \<=10.5% (\>=64 mmol/mol and \<=91 mmol/mol) OR on single allowable AHA (allowable AHAs prior to screening are: metformin, α-glucosidase inhibitors, sulfonylureas and glinides) with a Visit 1/Screening HbA1C \>=7.5% and \<=10.0% (\>=58 mmol/mol and \<=86 mmol/mol) OR on low-dose dual combination therapy (≤50% of maximum labeled dose of an AHA) with allowable AHAs with a Visit 1/Screening HbA1C \>=7.5% and \<=10.0% (\>=58 mmol/mol and \<=86 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 (or have their partner agree 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 diabetic 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 (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 sodium glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4 inhibitors), bromocriptine (Cycloset™), colesevelam (Welchol™), any other 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 (7)

• Miller S, Krumins T, Zhou H, Huyck S, Johnson J, Golm G, Terra SG, Mancuso JP, Engel SS, Lauring B. Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study. Diabetes Ther. 2018 Feb;9(1):253-268. doi: 10.1007/s13300-017-0358-0. Epub 2018 Jan 8.

  PMID: 29313282 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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin; Sitagliptin Phosphate; 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

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: August 25, 2014
• First Posted: August 26, 2014
• Study Start: September 23, 2014
• Primary Completion: February 23, 2016
• Study Completion: February 23, 2016
• Last Updated: September 13, 2018
• Results First Posted: April 7, 2017

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share