Study of the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Participants With Type 2 Diabetes Mellitus (MK-8521-003)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus

Treatments: Drug: Liraglutide; Drug: MK-8521; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01982630

8521-003

Details and patient eligibility

About

This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM).

This study was modified by a protocol amendment to a 2-part trial to further test the safety and tolerability of MK-8521 at higher doses and to compare MK-8521 pharmacokinetics between participants with T2DM and healthy participants. An additional cohort of T2DM participants and a cohort of non-diabetic obese participants has been added.

Enrollment: 87 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male, or female of non-childbearing potential with Type 2 diabetes mellitus (Parts 1 and 2) or non-diabetic (Part 2)
• Body mass index (BMI) between: ≥27 and ≤40 kg/m^2
• A1C (average blood sugar for the past 2 to 3 months) value ≥7.0 and ≤11.0 % (Part 1) or ≥ 6.5 and ≤11.0 % (Part 2) at the time of screening (T2DM participants)
• A1C value <5.7 at the time of screening (non-diabetic subjects in Part 2 only)
• On a stable dose of metformin (≥1000 mg total daily dose) for at least 12 weeks at the time of screening (T2DM participants)

Exclusion criteria

• Mentally or legally incapacitated
• History of clinically significant psychiatric disorder of the last 5 years. Participants with situational depression may be enrolled in the trial at the discretion of the Investigator
• History of Type 1 diabetes mellitus or a history of ketoacidosis
• History of clinically significant gastrointestinal, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
• History of cardiovascular disease or cardiac conduction disorder
• History of cancer (malignancy). Exceptions may include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated ≥10 years prior to the pre-screening visit
• History of proliferative diabetic retinopathy or maculopathy
• Clinically significant diabetic autonomic neuropathy
• QTc interval ≥470 msec (for males) or ≥480 msec (for females)
• Clinical significant electrocardiogram (ECG) abnormality
• Positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
• On a weight loss program and is not weight-stable (weight stable is defined history of <5% change in body weight in the last 3 months
• On a weight loss medication or has undergone bariatric surgery
• Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit
• Participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit
• History of acute or chronic pancreatitis of any etiology
• Mean value for triplicate semi-recumbent systolic blood pressure >160 mm Hg and/or diastolic blood pressure >90 mm Hg (after at least a 10-minute seated rest) and blood pressure is considered unlikely to be below these limits by Day-1 (Randomization) with initiation or adjustment of antihypertensive medication
• Event of severe hypoglycemia with seizure or loss of consciousness in the past 12 months
• Treated with anti-hyperglycemic agents other than metformin within the last 12 weeks
• Previous exposure to any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. Byetta™, Victoza™ or investigational agents)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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87 participants in 8 patient groups, including a placebo group

Part 1: MK-8521 64/120 μg/day

Experimental group

Description:

Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14.

Treatment:

Drug: MK-8521

Part 1: MK-8521 34/72 μg/day

Experimental group

Description:

T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.

Treatment:

Drug: MK-8521

Part 1: Liraglutide 0.6/1.2/1.8 mg/day

Active Comparator group

Description:

T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14.

Treatment:

Drug: Liraglutide

Part 1: Placebo for MK-8521

Placebo Comparator group

Description:

T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days.

Treatment:

Drug: Placebo

Part 2: MK-8521 64/120/180/240/300 µg/day-T2DM

Experimental group

Description:

T2DM participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29.

Treatment:

Drug: MK-8521

Part 2: Liraglutide 0.6/1.2/1.8 mg/day-T2DM

Active Comparator group

Description:

T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29.

Treatment:

Drug: Liraglutide

Part 2: Placebo for MK-8521-T2DM

Placebo Comparator group

Description:

T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.

Treatment:

Drug: Placebo

Part 2: MK-8521 64/120 µg/day-Non-Diabetic Overweight/Obese

Experimental group

Description:

Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14.

Treatment:

Drug: MK-8521