A Preliminary Study of the Efficacy and Safety of MK-8521 for Type 2 Diabetes (MK-8521-004)
Primary Purpose
Type II Diabetes Mellitus
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
MK-8521
Placebo
Liraglutide
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Type II Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Have T2DM in accordance with American Diabetes Association guidelines
- Be on metformin monotherapy (>-1000 mg/day: metformin IR or metformin XR) for at least 12 weeks prior to study start with a hemoglobin A1C (A1C) >-7.5 and <-10.5% OR Be on dual therapy with metformin (>-1000 mg/day: dose stable for at least 4 weeks prior to study start) with an A1C of >-7.0% and <-10.0% and a second AHA and be willing to washout the second AHA. Allowable AHAs are dipeptidyl peptidase 4 (DPP-4 inhibitors), alpha-glucosidase inhibitors, sulfonylureas, and glinides.
- Have a body mass index (BMI) ≥23 kg/m^2 and ≤40 kg/m^2
- Is a female who is not of reproductive potential, or is a female of reproductive potential who agrees to avoid becoming pregnant: while receiving study drug and for 14 days after the last dose of study drug
Exclusion Criteria:
- Have a history of type 1 diabetes or a history of diabetic ketoacidosis
- Has a 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)
- Has been treated with any gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) receptor agonist (e.g. Byetta™, Victoza™ or investigational agents) within the last 6 months or has had GLP-1 receptor agonist discontinued due to gastrointestinal intolerance or lack of efficacy. Note: treatment with a GLP-1 receptor agonist that was discontinued >6 months prior to study start is not an exclusion if the GLP-1 receptor agonist was discontinued for reasons other than gastrointestinal intolerance or lack of efficacy.
- Has a history of clinically significant gastrointestinal disorder (including diabetic gastroparesis; irritable bowel disease; recurrent episodes of nausea, vomiting, diarrhea and abdominal pain)
- Has a history of clinically significant and active, immunological, respiratory, genitourinary or major neurological (including stroke, transient ischemic attack and chronic seizures) abnormalities or diseases
- Has a history of cardiovascular disease (including diabetic cardiomyopathy) or significant cardiac condition (including a history of myocardial infarction, stable or unstable angina, arterial revascularization, pathologic, symptomatic or sustained tachyarrhythmia [e.g. atrial fibrillation, sustained supraventricular tachycardia, symptomatic non-sustained supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, Wolf-Parkinson-White syndrome, congenital long QT syndrome, etc.]) or heart failure
- Has a family history of medullary carcinoma of the thyroid or multiple endocrine neoplasm type-2 syndrome
- Has active diabetic proliferative retinopathy or a history of maculopathy
- Has human immunodeficiency virus (HIV)
- Has a medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic hepatitis B or C (assessed by medical history), primary biliary cirrhosis, or active symptomatic gallbladder disease
- Is on a weight loss medication or has undergone bariatric surgery
- Has a history of acute or chronic pancreatitis of any etiology
- Had an event of severe hypoglycemia with neuroglycopenia in the past 12 months
- Has a positive urine pregnancy test
- Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of investigational product
- Routinely consumes >1 alcoholic drinks per day or >7 alcoholic drinks per week or engages in binge drinking
- Routinely consumes ≥480mg /day caffeine in caffeinated beverages (1 cup of coffee contains approximately 120 mg of caffeine
- Is taking a beta blocker or medications with sympathomimetic activity (e.g. pseudoephedrine, phenylpropanolamine, etc.)
- Is currently a user of nicotine or nicotine containing products or does not agree to refrain from using nicotine during the trial, including 14 days following the last dose of investigational product
- Is currently a user of any illicit drugs (including any marijuana use) or has a history of drug (including alcohol) abuse within approximately 5 years
- has other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or blinded investigational product administration
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Active Comparator
Arm Label
MK-8521 300 μg
MK-8521 180 μg
Placebo
Liraglutide 1.8 mg
Arm Description
Participants receive double-blind MK-8521 300 μg daily (QD), subcutaneously, over 12 weeks.
Participants receive double-blind MK-8521 180 μg QD, subcutaneously, over 12 weeks.
Participants receive matching double-blind placebo, QD over 12 weeks.
Participants receive open-label 1.8 mg of liraglutide, QD, subcutaneously, over 12 weeks.
Outcomes
Primary Outcome Measures
Change From Baseline in Hemoglobin A1C (A1C) at Week 12
A1C is the percentage of hemoglobin that has glucose bound to it and is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is reported as a percentage (%). This change from baseline reflects the Week 12 A1C minus the Week 0 A1C.
Number of Participants With an Adverse Event (AE)
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.
Number of Participants Who Discontinued Study Treatment Due to an AE
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.
Number of Participants With an AE of Symptomatic Hypoglycemia
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. Hypoglycemia episodes are those with glucose values ≤70 mg/dL (3.9 mmol/L). Symptomatic hypoglycemia episodes were episodes with clinical symptoms reported by the investigator as hypoglycemia and classified as adverse events.
Change From Baseline in Heart Rate at Week 12
This change from baseline reflects the Week 12 heart rate minus the Week 0 heart rate.
Secondary Outcome Measures
Change From Baseline in Body Weight at Week 12
This change from baseline reflects the Week 12 body weight minus the Week 0 body weight.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
This change from baseline reflects the Week 12 FPG minus the Week 0 FPG.
Change From Baseline in Fasting Low Density Lipoprotein (LDL) Cholesterol at Week 12
This change from baseline reflects the Week 12 fasting LDL cholesterol minus the Week 0 fasting LDL cholesterol.
Change From Baseline in Fasting High Density Lipoprotein (HDL) Cholesterol at Week 12
This change from baseline reflects the Week 12 fasting HDL cholesterol minus the Week 0 fasting HDL cholesterol.
Change From Baseline in Fasting Triglycerides at Week 12
This change from baseline reflects the Week 12 fasting triglycerides minus the Week 0 fasting triglycerides.
Change From Baseline in Systolic Blood Pressure (SBP) at Week 12
This change from baseline reflects the Week 12 SBP minus the Week 0 SBP.
Change From Baseline in Diastolic Blood Pressure (DBP) at Week 12
This change from baseline reflects the Week 12 DBP minus the Week 0 DBP.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02492763
Brief Title
A Preliminary Study of the Efficacy and Safety of MK-8521 for Type 2 Diabetes (MK-8521-004)
Official Title
A Phase IIa, Multicenter, Placebo- and Active-controlled, Randomized, Double-Blind, Clinical Trial to Evaluate the Safety and Efficacy of MK-8521 Compared to Placebo in Subjects With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Study Start Date
July 27, 2015 (Actual)
Primary Completion Date
April 18, 2017 (Actual)
Study Completion Date
April 18, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a multicenter randomized, double-blind, placebo- and active-controlled (liraglutide; Victoza®), parallel-group, clinical trial of MK-8521 in participants with type 2 diabetes mellitus (T2DM) with inadequate glycemic control while on a stable dose of metformin (≥1000 mg/day).
The trial will include a 1-week screening period; at least an 8-week antihyperglycemic agent (AHA) washout period, if required; a 14-week blinded therapy period (which includes single-blind run-in and double-blind therapy); and a 14-day post-treatment visit, 2 weeks after the last dose of investigational product.
The primary hypothesis of the trial is that MK-8521 provides greater reduction in hemoglobin A1C relative to placebo after 12 weeks of once-daily administration in participants with T2DM with inadequate glycemic control on metformin monotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type II Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
176 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK-8521 300 μg
Arm Type
Experimental
Arm Description
Participants receive double-blind MK-8521 300 μg daily (QD), subcutaneously, over 12 weeks.
Arm Title
MK-8521 180 μg
Arm Type
Experimental
Arm Description
Participants receive double-blind MK-8521 180 μg QD, subcutaneously, over 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants receive matching double-blind placebo, QD over 12 weeks.
Arm Title
Liraglutide 1.8 mg
Arm Type
Active Comparator
Arm Description
Participants receive open-label 1.8 mg of liraglutide, QD, subcutaneously, over 12 weeks.
Intervention Type
Drug
Intervention Name(s)
MK-8521
Intervention Description
Dose strengths: 180 μg QD administered subcutaneously. A 2-step dose escalation regimen [60 μg, 120 μg] over the first 2 weeks is used to achieve the final dose up to 180 μg.); 300 μg QD administered subcutaneously (A 3-step dose escalation regimen [60 μg, 120 μg, 180 μg] over the first 3 weeks is used to achieve the final dose up to 300 μg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Double dummy matching placebo for the MK-8521 and placebo arms: matching placebo for MK-8521 300 μg QD administered subcutaneously; matching placebo for MK-8521 180 μg QD administered subcutaneously. A dose escalation regimen consistent with that of the MK-8521 300 μg and 180 μg arms of the study; mock escalation will be performed over the first 2 to 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Other Intervention Name(s)
Victoza®
Intervention Description
Dose strength: 1.8 mg QD administered subcutaneously. A 2-step dose escalation regimen (0.6 mg, 1.2 mg) over the first 2 weeks is used to achieve the final dose up to 1.8 mg.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Metformin immediate release (IR) or metformin extended release (XR) administered ≥1000 mg QD as background therapy
Primary Outcome Measure Information:
Title
Change From Baseline in Hemoglobin A1C (A1C) at Week 12
Description
A1C is the percentage of hemoglobin that has glucose bound to it and is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is reported as a percentage (%). This change from baseline reflects the Week 12 A1C minus the Week 0 A1C.
Time Frame
Baseline and Week 12
Title
Number of Participants With an Adverse Event (AE)
Description
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.
Time Frame
Up to Week 14
Title
Number of Participants Who Discontinued Study Treatment Due to an AE
Description
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.
Time Frame
Up to Week 12
Title
Number of Participants With an AE of Symptomatic Hypoglycemia
Description
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. Hypoglycemia episodes are those with glucose values ≤70 mg/dL (3.9 mmol/L). Symptomatic hypoglycemia episodes were episodes with clinical symptoms reported by the investigator as hypoglycemia and classified as adverse events.
Time Frame
Up to Week 14
Title
Change From Baseline in Heart Rate at Week 12
Description
This change from baseline reflects the Week 12 heart rate minus the Week 0 heart rate.
Time Frame
Baseline and Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Body Weight at Week 12
Description
This change from baseline reflects the Week 12 body weight minus the Week 0 body weight.
Time Frame
Baseline and Week 12
Title
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
Description
This change from baseline reflects the Week 12 FPG minus the Week 0 FPG.
Time Frame
Baseline and Week 12
Title
Change From Baseline in Fasting Low Density Lipoprotein (LDL) Cholesterol at Week 12
Description
This change from baseline reflects the Week 12 fasting LDL cholesterol minus the Week 0 fasting LDL cholesterol.
Time Frame
Baseline and Week 12
Title
Change From Baseline in Fasting High Density Lipoprotein (HDL) Cholesterol at Week 12
Description
This change from baseline reflects the Week 12 fasting HDL cholesterol minus the Week 0 fasting HDL cholesterol.
Time Frame
Baseline and Week 12
Title
Change From Baseline in Fasting Triglycerides at Week 12
Description
This change from baseline reflects the Week 12 fasting triglycerides minus the Week 0 fasting triglycerides.
Time Frame
Baseline and Week 12
Title
Change From Baseline in Systolic Blood Pressure (SBP) at Week 12
Description
This change from baseline reflects the Week 12 SBP minus the Week 0 SBP.
Time Frame
Baseline and Week 12
Title
Change From Baseline in Diastolic Blood Pressure (DBP) at Week 12
Description
This change from baseline reflects the Week 12 DBP minus the Week 0 DBP.
Time Frame
Baseline and Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have T2DM in accordance with American Diabetes Association guidelines
Be on metformin monotherapy (>-1000 mg/day: metformin IR or metformin XR) for at least 12 weeks prior to study start with a hemoglobin A1C (A1C) >-7.5 and <-10.5% OR Be on dual therapy with metformin (>-1000 mg/day: dose stable for at least 4 weeks prior to study start) with an A1C of >-7.0% and <-10.0% and a second AHA and be willing to washout the second AHA. Allowable AHAs are dipeptidyl peptidase 4 (DPP-4 inhibitors), alpha-glucosidase inhibitors, sulfonylureas, and glinides.
Have a body mass index (BMI) ≥23 kg/m^2 and ≤40 kg/m^2
Is a female who is not of reproductive potential, or is a female of reproductive potential who agrees to avoid becoming pregnant: while receiving study drug and for 14 days after the last dose of study drug
Exclusion Criteria:
Have a history of type 1 diabetes or a history of diabetic ketoacidosis
Has a 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)
Has been treated with any gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) receptor agonist (e.g. Byetta™, Victoza™ or investigational agents) within the last 6 months or has had GLP-1 receptor agonist discontinued due to gastrointestinal intolerance or lack of efficacy. Note: treatment with a GLP-1 receptor agonist that was discontinued >6 months prior to study start is not an exclusion if the GLP-1 receptor agonist was discontinued for reasons other than gastrointestinal intolerance or lack of efficacy.
Has a history of clinically significant gastrointestinal disorder (including diabetic gastroparesis; irritable bowel disease; recurrent episodes of nausea, vomiting, diarrhea and abdominal pain)
Has a history of clinically significant and active, immunological, respiratory, genitourinary or major neurological (including stroke, transient ischemic attack and chronic seizures) abnormalities or diseases
Has a history of cardiovascular disease (including diabetic cardiomyopathy) or significant cardiac condition (including a history of myocardial infarction, stable or unstable angina, arterial revascularization, pathologic, symptomatic or sustained tachyarrhythmia [e.g. atrial fibrillation, sustained supraventricular tachycardia, symptomatic non-sustained supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, Wolf-Parkinson-White syndrome, congenital long QT syndrome, etc.]) or heart failure
Has a family history of medullary carcinoma of the thyroid or multiple endocrine neoplasm type-2 syndrome
Has active diabetic proliferative retinopathy or a history of maculopathy
Has human immunodeficiency virus (HIV)
Has a medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic hepatitis B or C (assessed by medical history), primary biliary cirrhosis, or active symptomatic gallbladder disease
Is on a weight loss medication or has undergone bariatric surgery
Has a history of acute or chronic pancreatitis of any etiology
Had an event of severe hypoglycemia with neuroglycopenia in the past 12 months
Has a positive urine pregnancy test
Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of investigational product
Routinely consumes >1 alcoholic drinks per day or >7 alcoholic drinks per week or engages in binge drinking
Routinely consumes ≥480mg /day caffeine in caffeinated beverages (1 cup of coffee contains approximately 120 mg of caffeine
Is taking a beta blocker or medications with sympathomimetic activity (e.g. pseudoephedrine, phenylpropanolamine, etc.)
Is currently a user of nicotine or nicotine containing products or does not agree to refrain from using nicotine during the trial, including 14 days following the last dose of investigational product
Is currently a user of any illicit drugs (including any marijuana use) or has a history of drug (including alcohol) abuse within approximately 5 years
has other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or blinded investigational product administration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Learn more about this trial
A Preliminary Study of the Efficacy and Safety of MK-8521 for Type 2 Diabetes (MK-8521-004)
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