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

NCT02492763 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 8521-004MK-8521-004
• Study Type: interventional
• Target: 176
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (5)

• 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.

  Baseline and Week 12

• 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.

  Up to Week 14

• 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.

  Up to Week 12

• 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.

  Up to Week 14

• 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.

  Baseline and Week 12

Secondary Outcomes (7)

• Change From Baseline in Body Weight at Week 12

  Baseline and Week 12

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12

  Baseline and Week 12

• Change From Baseline in Fasting Low Density Lipoprotein (LDL) Cholesterol at Week 12

  Baseline and Week 12

• Change From Baseline in Fasting High Density Lipoprotein (HDL) Cholesterol at Week 12

  Baseline and Week 12

• Change From Baseline in Fasting Triglycerides at Week 12

  Baseline and Week 12

Study Arms (4)

MK-8521 300 μg

EXPERIMENTAL

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

Drug: MK-8521; Drug: Placebo; Drug: Metformin

MK-8521 180 μg

EXPERIMENTAL

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

Drug: MK-8521; Drug: Placebo; Drug: Metformin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Metformin

Liraglutide 1.8 mg

ACTIVE COMPARATOR

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

Drug: Liraglutide; Drug: Metformin

Interventions

MK-8521 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.

MK-8521 180 μg; MK-8521 300 μg

Placebo 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.

MK-8521 180 μg; MK-8521 300 μg; Placebo

Liraglutide 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.

Also known as: Victoza®

Liraglutide 1.8 mg

Metformin DRUG

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

Liraglutide 1.8 mg; MK-8521 180 μg; MK-8521 300 μg; Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Liraglutide; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Biguanides; Guanidines; Amidines; Organic Chemicals

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 9, 2015
• Study Start: July 27, 2015
• Primary Completion: April 18, 2017
• Study Completion: April 18, 2017
• Last Updated: September 10, 2018
• Results First Posted: March 8, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share