A Preliminary Study of the Efficacy and Safety of MK-8521 for Type 2 Diabetes (MK-8521-004)

NCT ID: NCT02492763

Last Updated: 2018-09-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-27
• Study Completion Date: 2017-04-18

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.

Conditions

Type II Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

MK-8521 300 μg

Participants receive double-blind MK-8521 300 μg daily (QD), subcutaneously, over 12 weeks.

Group Type: EXPERIMENTAL

MK-8521

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

Metformin

Intervention Type: DRUG

Metformin immediate release (IR) or metformin extended release (XR) administered ≥1000 mg QD as background therapy

MK-8521 180 μg

Participants receive double-blind MK-8521 180 μg QD, subcutaneously, over 12 weeks.

Group Type: EXPERIMENTAL

MK-8521

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

Metformin

Intervention Type: DRUG

Metformin immediate release (IR) or metformin extended release (XR) administered ≥1000 mg QD as background therapy

Placebo

Participants receive matching double-blind placebo, QD over 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Metformin

Intervention Type: DRUG

Metformin immediate release (IR) or metformin extended release (XR) administered ≥1000 mg QD as background therapy

Liraglutide 1.8 mg

Participants receive open-label 1.8 mg of liraglutide, QD, subcutaneously, over 12 weeks.

Group Type: ACTIVE_COMPARATOR

Liraglutide

Intervention Type: DRUG

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.

Metformin

Intervention Type: DRUG

Metformin immediate release (IR) or metformin extended release (XR) administered ≥1000 mg QD as background therapy

Interventions

MK-8521

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

Placebo

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

Liraglutide

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

Metformin

Metformin immediate release (IR) or metformin extended release (XR) administered ≥1000 mg QD as background therapy

Intervention Type: DRUG

Other Intervention Names

Victoza®

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-8521-004

Identifier Type: OTHER

Identifier Source: secondary_id

8521-004

Identifier Type: -

Identifier Source: org_study_id