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)

NCT ID: NCT02269735

Last Updated: 2019-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-26
• Study Completion Date: 2016-07-29

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part I: MK-2640 (Panel A)

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

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part I: MK-2640 (Panel B)

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

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part I: MK-2640 (Panel C)

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

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part I: MK-2640 (Panel D)

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

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part I: MK-2640 (Panel E)

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

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part I: MK-2640 (Panel F)

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

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part I: MK-2640 (Panel G)

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

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part II: MK-2640 followed by RHI

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.

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Regular Human Insulin (RHI)

Intervention Type: BIOLOGICAL

RHI 100 units/mL intravenous infusion to maintain target glycemic level

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Insulin aspart

Intervention Type: BIOLOGICAL

Insulin aspart subcutaneous injection or intravenous infusion the evening before each period in Parts II and III to achieve/maintain glycemic target.

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part II: RHI followed by MK-2640

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.

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Regular Human Insulin (RHI)

Intervention Type: BIOLOGICAL

RHI 100 units/mL intravenous infusion to maintain target glycemic level

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Insulin aspart

Intervention Type: BIOLOGICAL

Insulin aspart subcutaneous injection or intravenous infusion the evening before each period in Parts II and III to achieve/maintain glycemic target.

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part III: MK-2640 followed by RHI

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.

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Regular Human Insulin (RHI)

Intervention Type: BIOLOGICAL

RHI 100 units/mL intravenous infusion to maintain target glycemic level

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Insulin aspart

Intervention Type: BIOLOGICAL

Insulin aspart subcutaneous injection or intravenous infusion the evening before each period in Parts II and III to achieve/maintain glycemic target.

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Part III: RHI followed by MK-2640

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.

Group Type: EXPERIMENTAL

MK-2640

Intervention Type: DRUG

MK-2640 intravenous infusion administered to participant in a fasted state

Regular Human Insulin (RHI)

Intervention Type: BIOLOGICAL

RHI 100 units/mL intravenous infusion to maintain target glycemic level

Dextrose

Intervention Type: DRUG

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Insulin aspart

Intervention Type: BIOLOGICAL

Insulin aspart subcutaneous injection or intravenous infusion the evening before each period in Parts II and III to achieve/maintain glycemic target.

Rescue medication

Intervention Type: DRUG

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Interventions

MK-2640

MK-2640 intravenous infusion administered to participant in a fasted state

Intervention Type: DRUG

Regular Human Insulin (RHI)

RHI 100 units/mL intravenous infusion to maintain target glycemic level

Intervention Type: BIOLOGICAL

Dextrose

Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level

Intervention Type: DRUG

Insulin aspart

Insulin aspart subcutaneous injection or intravenous infusion the evening before each period in Parts II and III to achieve/maintain glycemic target.

Intervention Type: BIOLOGICAL

Rescue medication

Rescue medication may be administered for hypotension or mild to moderate infusion reaction. Rescue medication may include epinephrine, antihistamines, steroids, or acetaminophen/paracetamol.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Krug AW, Visser SAG, Tsai K, Kandala B, Fancourt C, Thornton B, Morrow L, Kaarsholm NC, Bernstein HS, Stoch SA, Crutchlow M, Kelley DE, Iwamoto M. Clinical Evaluation of MK-2640: An Insulin Analog With Glucose-Responsive Properties. Clin Pharmacol Ther. 2019 Feb;105(2):417-425. doi: 10.1002/cpt.1215. Epub 2018 Sep 30.

Reference Type: RESULT

PMID: 30125349 (View on PubMed)

Other Identifiers

2640-001

Identifier Type: -

Identifier Source: org_study_id