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)

Type 1 Diabetes Mellitus Clinical Trial

Official title:

A Three-part Study Parts I, II and III: Rising Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Healthy Subjects (Part I) and Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Subjects With Type 1 Diabetes Mellitus (Part II and Part III).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02269735
• Other study ID #: 2640-001
• Status: Completed
• Phase: Phase 1
• Start date: November 26, 2014
• Est. completion date: July 29, 2016

Study information

• Verified date: January 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: July 29, 2016
• Est. primary completion date: July 29, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

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

Biological:
• Regular Human Insulin (RHI)
RHI 100 units/mL intravenous infusion to maintain target glycemic level

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

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

Drug:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who experienced an adverse event		Up to 30 days following last dose
Primary	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
Primary	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
Primary	Pharmacokinetic parameter: clearance (CL)		Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval
Primary	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
Primary	Pharmacokinetic parameter: plasma apparent terminal half-life		Part II: following 9 hour infusion; Part III: following 7 hour infusion
Primary	Pharmacodynamic parameter: steady-state glucose infusion-rate (GIR) in Part II		Part II: during the final 60 minutes of the infusion
Primary	Number of participants who discontinued study drug due to an adverse event		Part I: 1 day; Parts II and III: 9 days
Secondary	Number of participants with anti-drug antibody (ADA) formation		Up to 30 days following last dose