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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)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02269735
First Posted: October 21, 2014
Last Update Posted: August 19, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose
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.

Condition Intervention Phase
Type 1 Diabetes Mellitus Drug: MK-2640 Biological: Regular Human Insulin (RHI) Drug: Dextrose Biological: Insulin aspart Drug: Rescue medication Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of participants who experienced an adverse event [ Time Frame: Up to 30 days following last dose ]
  • Pharmacokinetic parameter: steady state plasma concentration (Css) [ Time Frame: 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]) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Part II: following 9 hour infusion; Part III: following 7 hour infusion ]
  • Pharmacodynamic parameter: steady-state glucose infusion-rate (GIR) in Part II [ Time Frame: Part II: during the final 60 minutes of the infusion ]
  • Number of participants who discontinued study drug due to an adverse event [ Time Frame: Part I: 1 day; Parts II and III: 9 days ]

Secondary Outcome Measures:
  • Number of participants with anti-drug antibody (ADA) formation [ Time Frame: Up to 30 days following last dose ]

Enrollment: 74
Study Start Date: November 2014
Study Completion Date: July 2016
Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: MK-2640
MK-2640 intravenous infusion administered to participant in a fasted state
Drug: Dextrose
Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level
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.
Experimental: 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.
Drug: MK-2640
MK-2640 intravenous infusion administered to participant in a fasted state
Drug: Dextrose
Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level
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.
Experimental: 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.
Drug: MK-2640
MK-2640 intravenous infusion administered to participant in a fasted state
Drug: Dextrose
Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level
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.
Experimental: 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.
Drug: MK-2640
MK-2640 intravenous infusion administered to participant in a fasted state
Drug: Dextrose
Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level
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.
Experimental: 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.
Drug: MK-2640
MK-2640 intravenous infusion administered to participant in a fasted state
Drug: Dextrose
Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level
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.
Experimental: 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.
Drug: MK-2640
MK-2640 intravenous infusion administered to participant in a fasted state
Drug: Dextrose
Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level
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.
Experimental: 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.
Drug: MK-2640
MK-2640 intravenous infusion administered to participant in a fasted state
Drug: Dextrose
Dextrose 20% or 50% intravenous infusion for approximately 9 or 7 hours, as appropriate to attain a target glycemic level
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.
Experimental: 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.
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.
Experimental: 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.
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.
Experimental: 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.
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.
Experimental: 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.
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02269735


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02269735     History of Changes
Other Study ID Numbers: 2640-001
First Submitted: October 16, 2014
First Posted: October 21, 2014
Last Update Posted: August 19, 2016
Last Verified: August 2016

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin degludec, insulin aspart drug combination
Insulin
Insulin Aspart
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs