Type 1 Diabetes Mellitus
Conditions
Brief summary
The purpose of Part I of this study is to evaluate the safety and tolerability of intravenous (IV) doses of MK-2640 in healthy participants and to obtain preliminary plasma pharmacokinetic profiles of MK-2640. The purpose of Parts II and III of this study is to evaluate the safety and tolerability of IV doses of MK-2640 and regular human insulin (RHI), and to evaluate the pharmacokinetic and pharmacodynamic profile of MK-2640 and RHI in participants with type 1 diabetes mellitus (T1DM). Part II will be initiated only if Part I general safety, tolerability and other observed data are supportive of progression to Part II. Part III will be initiated only if Parts I and II general safety, tolerability and other observed data are supportive of progression to Part III.
Interventions
DRUGMK-2640
MK-2640 intravenous infusion administered to participant in a fasted state
BIOLOGICALRegular Human Insulin (RHI)
RHI 100 units/mL intravenous infusion to maintain target glycemic level
DRUGDextrose
Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level
BIOLOGICALInsulin aspart
Insulin aspart subcutaneous injection or intravenous infusion the evening before each period in Parts II and III to achieve/maintain glycemic target.
DRUGRescue medication
Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
(Part I): * healthy male or healthy female of non-child bearing potential * in good health * is a non-smoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months Inclusion Criteria (Parts II and III): * male or female of non-child bearing potential * has T1DM for at least 12 months * on stable doses of insulin * in good health * is a nonsmoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months
Exclusion criteria
* is mentally or legally incapacitated, or has significant emotional problems at the time of screening visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years * has a history of clinically significant endocrine (except T1DM for Part II subjects), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases * is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV) * has a history of cancer (malignancy), except adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix * has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food, had major surgery, donated or lost 1 unit of blood within 4 weeks prior to the screening visit * has participated in another investigational trial within 4 weeks prior to the screening visit * is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of trial drug, throughout the trial, until the posttrial visit * consumes greater than 3 glasses of alcoholic beverages daily * consumes greater than 6 servings of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day. * is currently a regular or recreational user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants who discontinued study drug due to an adverse event | Part I: 1 day; Parts II and III: 9 days |
| Number of participants who experienced an adverse event | Up to 30 days following last dose |
| Pharmacokinetic parameter: steady state plasma concentration (Css) | Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval |
| Pharmacokinetic parameter: area under the plasma concentration curve from time 0 to infinity (AUC [0 to infinity]) | Part I: 18 time points between predose and 600 minutes (min.); Part II: 19 time points between predose and 535 min.; Part III: 18 time points between predose and 415 min. following start of infusion |
| Pharmacokinetic parameter: clearance (CL) | Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval |
| Pharmacokinetic parameter: volume of distribution (Vd) | Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval |
| Pharmacokinetic parameter: plasma apparent terminal half-life | Part II: following 9 hour infusion; Part III: following 7 hour infusion |
| Pharmacodynamic parameter: steady-state glucose infusion-rate (GIR) in Part II | Part II: during the final 60 minutes of the infusion |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with anti-drug antibody (ADA) formation | Up to 30 days following last dose |
Outcome results
None listed