Type 2 Diabetes Mellitus
Conditions
Brief summary
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).
Interventions
DRUGMK-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.
OTHERPlacebo
Matching placebo to MK-5823 administered subcutaneously once daily for 3 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Lowest plasma concentration (Ctrough) following once daily administration of MK-5823 | Predose on Day 1 (baseline) through 672 hours following the initial dose |
| 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 |
| 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 |
| 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 |
| Maximum plasma concentration (Cmax) following once daily administration of MK-5823 | Predose on Day 1 (baseline) through 672 hours following the initial dose |
Outcome results
None listed