Clinical trial NCT02492763: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Type II Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-07-09
Enrollment: 176
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1C (A1C) at Week 12
timeFrame: Baseline and Week 12
measure: Number of Participants With an Adverse Event (AE)
timeFrame: Up to Week 14
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to Week 12
measure: Number of Participants With an AE of Symptomatic Hypoglycemia
timeFrame: Up to Week 14
measure: Change From Baseline in Heart Rate at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in Body Weight at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Fasting Low Density Lipoprotein (LDL) Cholesterol at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Fasting High Density Lipoprotein (HDL) Cholesterol at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Fasting Triglycerides at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Systolic Blood Pressure (SBP) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Diastolic Blood Pressure (DBP) at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: