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)

January 11, 2019 updated by: Merck Sharp & Dohme LLC

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).

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
74

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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.
Biological: Regular Human Insulin (RHI)
RHI 100 units/mL intravenous infusion to maintain 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.
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
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.
Biological: Regular Human Insulin (RHI)
RHI 100 units/mL intravenous infusion to maintain 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.
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
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.
Biological: Regular Human Insulin (RHI)
RHI 100 units/mL intravenous infusion to maintain 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.
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
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.
Biological: Regular Human Insulin (RHI)
RHI 100 units/mL intravenous infusion to maintain 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of participants who experienced an adverse event
Time Frame: Up to 30 days following last dose
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
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
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
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
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
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
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
Part I: 1 day; Parts II and III: 9 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Number of participants with anti-drug antibody (ADA) formation
Time Frame: Up to 30 days following last dose
Up to 30 days following last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 26, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 29, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 29, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 16, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 21, 2014

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 15, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2640-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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