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)

August 15, 2018 updated by: Merck Sharp & Dohme LLC

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of the Initial Combination of Ertugliflozin (MK-8835/PF-04971729) With Sitagliptin in the Treatment of Subjects With T2DM With Inadequate Glycemic Control on Diet and Exercise

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Each participant will be in the study for approximately 39 weeks including: a 1-week screening period, an 8-week (or greater) antihyperglycemic agent (AHA) wash-off period, 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

Interventional

Enrollment (Actual)

291

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • On a previous clinical study with ertugliflozin
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ertugliflozin 5 mg and Sitagliptin 100 mg
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
Ertugliflozin, 5 mg or 15 mg, administered orally, once daily for 26 weeks.
Drug: Sitagliptin
Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Drug: Placebo to Ertugliflozin
Matching placebo to ertugliflozin administered orally, once daily for 26 weeks.
Drug: Glimepiride
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.
Experimental: Ertugliflozin 15 mg and Sitagliptin 100 mg
Ertugliflozin, 15 mg, administered orally, once daily for 26 weeks. Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Drug: Ertugliflozin
Ertugliflozin, 5 mg or 15 mg, administered orally, once daily for 26 weeks.
Drug: Sitagliptin
Sitagliptin, 100 mg, administered orally, once daily for 26 weeks.
Drug: Glimepiride
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.
Placebo Comparator: Placebo to Ertugliflozin and Placebo to Sitagliptin
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
Matching placebo to ertugliflozin administered orally, once daily for 26 weeks.
Drug: Glimepiride
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.
Drug: Placebo to Sitagliptin
Matching placebo to sitagliptin administered orally, once daily for 26 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Hemoglobin A1C (HbA1C) at Week 26 - Full Analysis Set (FAS Population Excluding Rescue Approach
Time Frame: Baseline and Week 26
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
Time Frame: Up to Week 28
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
Time Frame: Up to Week 26
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 - Full Analysis Set Excluding Rescue Approach
Time Frame: Baseline and Week 26
Blood glucose was measured after a ≥10 hour fast. Blood was drawn at predose on Day 1 and after 26 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 26 minus FPG at baseline). 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
Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 26 - Full Analysis Set Excluding Rescue Approach
Time Frame: Baseline and Week 26
Change from baseline at Week 26 is defined as 2-hour PMG at Week 26 minus 2-hour PMG at Week 0. Two-hour post-meal glucose was measured following a standard meal. 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 With HbA1C <7% (<53 mmol/Mol) at Week 26
Time Frame: Week 26
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.
Week 26
Change From Baseline in Body Weight at Week 26 - Full Analysis Set Excluding Rescue Approach
Time Frame: Baseline and Week 26
Body weight was measured using a standardized, digital scale at each of the pre-defined nominal time points. Weight was taken in duplicate throughout the trial at approximately the same time of day, after voiding (i.e., forced void) and while wearing only a gown and underwear. 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
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 - Full Analysis Set Excluding Rescue Approach
Time Frame: Baseline and Week 26
Blood pressure measurements were taken after at least 5 minutes of rest. Three measurements were taken approximately 2 minutes apart with the triplicate set recorded. 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
Change From Baseline in Sitting Diastolic Blood Pressure at Week 26 - Full Analysis Set Excluding Rescue Approach
Time Frame: Baseline and Week 26
Blood pressure measurements were taken after at least 5 minutes of rest. Three measurements were taken approximately 2 minutes apart with the triplicate set recorded. 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2014

Primary Completion (Actual)

February 23, 2016

Study Completion (Actual)

February 23, 2016

Study Registration Dates

First Submitted

August 25, 2014

First Submitted That Met QC Criteria

August 25, 2014

First Posted (Estimate)

August 26, 2014

Study Record Updates

Last Update Posted (Actual)

September 13, 2018

Last Update Submitted That Met QC Criteria

August 15, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8835-017
  • 2014-001049-25 (EudraCT Number)
  • B1521047 (Other Identifier: Pfizer Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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