A Three-part Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Healthy Participants (Part I) and Participants With Type 1 Diabetes Mellitus (Parts II and III) (MK-2640-001)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Type 1 Diabetes Mellitus

Treatments: Biological: Regular Human Insulin (RHI); Drug: Dextrose; Biological: Insulin aspart; Drug: Rescue medication; Drug: MK-2640

Study type: Interventional

Funder types: Industry

Identifiers

NCT02269735

2640-001

Details and patient eligibility

About

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.

Enrollment: 74 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Exclusion Criteria (Parts II and III):

• has a history of diabetic ketoacidosis in the last 6 months.
• has had one or more severe hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness within 2 weeks prior to dosing
• has used systemic (intravenous, oral, inhaled) glucocorticoids within 3 months of screening or is anticipated to require treatment with systemic glucocorticoids during study participation
• has a history of hypersensitivity to pharmacologic insulins or to any of the inactive ingredients in regular human insulin, or to any E. coli-derived drug product

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 11 patient groups

Part I: MK-2640 (Panel A)

Experimental group

Description:

Part I: Lowest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

Treatment:

Drug: MK-2640

Drug: Dextrose

Drug: Rescue medication

Part I: MK-2640 (Panel B)

Experimental group

Description:

Part I: Low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

Treatment:

Drug: MK-2640

Drug: Dextrose

Drug: Rescue medication

Part I: MK-2640 (Panel C)

Experimental group

Description:

Part I: Medium-low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

Treatment:

Drug: MK-2640

Drug: Dextrose

Drug: Rescue medication

Part I: MK-2640 (Panel D)

Experimental group

Description:

Part I: Medium dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

Treatment:

Drug: MK-2640

Drug: Dextrose

Drug: Rescue medication

Part I: MK-2640 (Panel E)

Experimental group

Description:

Part I: Medium-high dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

Treatment:

Drug: MK-2640

Drug: Dextrose

Drug: Rescue medication

Part I: MK-2640 (Panel F)

Experimental group

Description:

Part I: High dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

Treatment:

Drug: MK-2640

Drug: Dextrose

Drug: Rescue medication

Part I: MK-2640 (Panel G)

Experimental group

Description:

Part 1: Highest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

Treatment:

Drug: MK-2640

Drug: Dextrose

Drug: Rescue medication

Part II: MK-2640 followed by RHI

Experimental group

Description:

Part II: MK-2640 infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

Treatment:

Drug: MK-2640

Biological: Regular Human Insulin (RHI)

Drug: Dextrose

Biological: Insulin aspart

Drug: Rescue medication

Part II: RHI followed by MK-2640

Experimental group

Description:

Part II: RHI infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

Treatment:

Drug: MK-2640

Biological: Regular Human Insulin (RHI)

Drug: Dextrose

Biological: Insulin aspart

Drug: Rescue medication

Part III: MK-2640 followed by RHI

Experimental group

Description:

Part III: MK-2640 infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

Treatment:

Drug: MK-2640

Biological: Regular Human Insulin (RHI)

Drug: Dextrose

Biological: Insulin aspart

Drug: Rescue medication

Part III: RHI followed by MK-2640

Experimental group

Description:

Part III: RHI infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

Treatment:

Drug: MK-2640

Biological: Regular Human Insulin (RHI)

Drug: Dextrose

Biological: Insulin aspart

Drug: Rescue medication