A Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-5823 in Overweight or Obese Participants Who Are Healthy or Have Type 2 Diabetes Mellitus (MK-5823-002)

A Multiple Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-5823 in Healthy Overweight/Obese Subjects and Patients With Type 2 Diabetes Mellitus

The purpose of this study is to assess the multiple rising dose safety/tolerability and pharmacokinetics of MK-5823 in overweight/obese participants who are healthy and overweight/obese participants with Type 2 diabetes mellitus (T2DM).

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: MK-5823; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female of non-childbearing potential
• A Body Mass Index between 27 and 35 kg/m^2 and weighs at least 50 kg
• Judged to be in good health and for the T2DM Panels, good health other than the diagnosis of T2DM
• For T2DM Panels only: has a diagnosis of T2DM and is being treated with lifestyle management (e.g. diet and exercise) alone or in combination with a stable dose of metformin
• A nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months

Exclusion Criteria:

• History of stroke, chronic seizures or major neurological disorder
• History of clinically significant gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases.
• History of clinically significant endocrine abnormalities or diseases (including type I or type II, or steroid-induced diabetes for healthy participant panel; and excluding T2DM for the T2DM Panels)
• Irritable bowel syndrome, or recurrent nausea, vomiting, diarrhea, or abdominal pain.
• History of neoplastic disease
• History of cataracts, diabetic retinopathy, macular edema, macular degeneration, vitreous hemorrhage, glaucoma, ocular surgery, ocular trauma or blindness
• Requires treatment with systemic or ocular corticosteroids
• For T2DM Panels, a history of hypoglycemic unawareness
• For T2DM Panels, active treatment with any anti-hyperglycemic drug other than metformin
• For T2DM Panels, treatment with any peroxisome proliferator-activated receptor-gamma agonist (e.g. Avandia or Actos) within 12 weeks of study participation
• Unable to refrain from using any medication beginning 2 weeks before study participation
• Consumes excessive amounts of alcohol (>3 per day)
• Consumes more than 6 caffeinated beverages per day
• Had major surgery or donated or lost more than 1 unit of blood
• Participated in another investigational study within 4 weeks of study participation
• History of significant multiple and/or severe allergies or anaphylactic reaction
• Hypersensitivity to glucagon or insulin
• Uses illicit drugs or has a history of drug or alcohol abuse within 3 months of study participation
• Woman of child-bearing potential or is a nursing mother
• For T2DM Panels, age >50 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.35 mg MK-5823 - Healthy Participants	Drug: MK-5823; MK-5823 administered subcutaneously (doses ranging from 0.35 mg to 2.8 mg) once daily for 3 weeks. Doses may be adjusted downward based on safety, tolerability, and/or pharmacokinetic data. The decision to dose escalate will be based on accrued safety/tolerability data at the prior dose level. In each arm, 6 participants will be randomized to receive study drug and 2 participants will be randomized to receive placebo.; Other: Placebo; Matching placebo to MK-5823 administered subcutaneously once daily for 3 weeks.
Experimental: 0.7 mg MK-5823 - Healthy Participants	Drug: MK-5823; MK-5823 administered subcutaneously (doses ranging from 0.35 mg to 2.8 mg) once daily for 3 weeks. Doses may be adjusted downward based on safety, tolerability, and/or pharmacokinetic data. The decision to dose escalate will be based on accrued safety/tolerability data at the prior dose level. In each arm, 6 participants will be randomized to receive study drug and 2 participants will be randomized to receive placebo.; Other: Placebo; Matching placebo to MK-5823 administered subcutaneously once daily for 3 weeks.
Experimental: 1.4 mg MK-5823 - Healthy Participants	Drug: MK-5823; MK-5823 administered subcutaneously (doses ranging from 0.35 mg to 2.8 mg) once daily for 3 weeks. Doses may be adjusted downward based on safety, tolerability, and/or pharmacokinetic data. The decision to dose escalate will be based on accrued safety/tolerability data at the prior dose level. In each arm, 6 participants will be randomized to receive study drug and 2 participants will be randomized to receive placebo.; Other: Placebo; Matching placebo to MK-5823 administered subcutaneously once daily for 3 weeks.
Experimental: 2.8 mg MK-5823 - Healthy Participants	Drug: MK-5823; MK-5823 administered subcutaneously (doses ranging from 0.35 mg to 2.8 mg) once daily for 3 weeks. Doses may be adjusted downward based on safety, tolerability, and/or pharmacokinetic data. The decision to dose escalate will be based on accrued safety/tolerability data at the prior dose level. In each arm, 6 participants will be randomized to receive study drug and 2 participants will be randomized to receive placebo.; Other: Placebo; Matching placebo to MK-5823 administered subcutaneously once daily for 3 weeks.
Experimental: 1.4 mg MK-5823 - Participants with T2DM	Drug: MK-5823; MK-5823 administered subcutaneously (doses ranging from 0.35 mg to 2.8 mg) once daily for 3 weeks. Doses may be adjusted downward based on safety, tolerability, and/or pharmacokinetic data. The decision to dose escalate will be based on accrued safety/tolerability data at the prior dose level. In each arm, 6 participants will be randomized to receive study drug and 2 participants will be randomized to receive placebo.; Other: Placebo; Matching placebo to MK-5823 administered subcutaneously once daily for 3 weeks.
Experimental: 2.8 mg MK-5823 - Participants with T2DM	Drug: MK-5823; MK-5823 administered subcutaneously (doses ranging from 0.35 mg to 2.8 mg) once daily for 3 weeks. Doses may be adjusted downward based on safety, tolerability, and/or pharmacokinetic data. The decision to dose escalate will be based on accrued safety/tolerability data at the prior dose level. In each arm, 6 participants will be randomized to receive study drug and 2 participants will be randomized to receive placebo.; Other: Placebo; Matching placebo to MK-5823 administered subcutaneously once daily for 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants who experienced at least one adverse event	Up to 49 days
Number of participants who discontinued from study drug due to an adverse event	Up to 21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration time curve from Hour 0 to Hour 24 (AUC0-24) following once daily administration of MK-5823	Predose on Day 1 (baseline) through 672 hours following the initial dose
Maximum plasma concentration (Cmax) following once daily administration of MK-5823	Predose on Day 1 (baseline) through 672 hours following the initial dose
Lowest plasma concentration (Ctrough) following once daily administration of MK-5823	Predose on Day 1 (baseline) through 672 hours following the initial dose
Time to maximum plasma concentration (Tmax) following once daily administration of MK-5823	Predose on Day 1 (baseline) through 672 hours following the initial dose
Apparent terminal half-life (apparent t1/2) following once daily administration of MK-5823	Predose on Day 1 (baseline) through 672 hours following the initial dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: June 6, 2012
• First Submitted That Met QC Criteria: June 6, 2012
• First Posted (Estimate): June 8, 2012

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: February 3, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight
• Other Study ID Numbers: 5823-002