Back to resultsA Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1293 Compared With a Basal Insulin in Participants With Type 1 Diabetes (MK-1293-005)
Primary Purpose
Type 1 Diabetes Mellitus
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-1293
EU-Lantus™
Novolog™
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Has type 1 diabetes mellitus diagnosed at least 12 months before screening
- Subject to investigator discretion, is on a stable dose of insulin for at least 2 weeks before screening
- Has a total daily insulin dose <=1.2 units/kg
- Has a screening hemoglobin A1c <9.5%
- Has a body mass index >18.0 and <=30.0 kg/m^2
- Has a weight >=50 kg
- Female participant of reproductive potential has a serum beta-human chorionic gonadotropin level consistent with the nongravid state and agrees to use (and/or have her partner use) 2 acceptable methods of birth control until 2 weeks after the last dose of study drug
- Postmenopausal female participant is without menses for >=1 year
- Surgically sterile female participant status is post hysterectomy, oophorectomy, or tubal ligation
- Has not used nicotine or nicotine-containing products for at least 3 months before study start or smokes less than 10 cigarettes per day and is willing to abstain during the trial
Exclusion Criteria:
- Has a history of clinically significant gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- Has a history of clinically significant endocrine abnormalities or diseases except type 1 diabetes mellitus
- Has had any severe hypoglycemic episodes associated with hypoglycemic seizures, comas, or unconsciousness within the past 3 months
- Has a history of diabetic ketoacidosis within the past 6 months
- Has a history of significant multiple or severe allergies, anaphylactic reaction, or significant intolerability to drugs or food
- Has a history of hypersensitivity to pharmacologic insulins
- Is positive for hepatitis B surface antigen, hepatitis C, or Human Immunodeficiency Virus
- Has had major surgery or donated or lost 1 unit of blood within 4 weeks before screening
- Unable to refrain from use of any medication or herbal remedy from 2 weeks prior to the first dose of study drug to until the posttrial visit. Some medications are permitted and may be discussed with the investigators
- Vaccination within 12 weeks of start of study participation
- Consumes >3 glasses of alcoholic beverages per day. Participants consuming 4 glasses of alcoholic beverages may be enrolled at the discretion of the investigator.
- Consumes >6 servings of caffeinated beverages per day
- Is a regular user of any illicit drugs or has a history of drug abuse (including alcohol) within approximately 1 year
- Is on a carbohydrate-restricted diet (<100 grams carbohydrate per day); participants who are on a carbohydrate-restricted diet may be included if they agree to a diet consisting of >=100 grams of carbohydrate daily throughout the study
- Has a personal or family history of hypercoagulability or thromboembolic disease
- Has used systemic glucocorticoids within 3 months of screening or anticipates treatment with systemic glucocorticoids during study participation.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™
EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293
Arm Description
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
Outcomes
Primary Outcome Measures
Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
Duration of Action (DOA) is defined as the length of time from dosing to End of Action. End of Action is defined as the time point at which plasma glucose has been above 150 mg/dL for 30 minutes and no glucose has been infused for 30 minutes. Median and max below are reported for the length of clamp duration (i.e. 30 hours).
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over 24 Hours After Dosing (GIR-AUC0-24hr)
The area under the glucose infusion rate curve from hours 0 to 24 after injection (AUC[GIR{0-24}]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the First 12 Hours After Dosing (GIR-AUC0-12hr)
The area under the glucose infusion rate curve from hours 0 to 12 after injection (AUC[GIR{0-12}]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the Second 12 Hours After Dosing (GIR-AUC12-24hr)
The area under the glucose infusion rate curve from hours 12 to 24 after injection (AUC[GIR{12-24}]) for participants who received either MK-1293 or Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Maximum Glucose Infusion Rate (GIRmax)
Maximum glucose infusion rate (GIR[max]) based on smoothed data for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
M1 Glargine Metabolite Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC0-24)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Analysis was performed on log scale with results back transformed to the original scale
M1 Glargine Metabolite PK: Maximum Plasma Concentration (Cmax)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Analysis was performed on log scale with results back transformed to original scale.
Secondary Outcome Measures
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the First 12 Hours After Dosing (AUC0-12)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-12 is a measure of the total amount of drug in the plasma from the dose to Hour 12. Analysis was performed on log scale with results back transformed to original scale.
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the Second 12 Hours After Dosing (AUC12-24)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC12-24 is a measure of the total amount of drug in the plasma from Hour 12 to Hour 24. Analysis was performed on log scale with results back transformed to original scale.
Full Information
NCT ID
NCT02059174
First Posted
February 7, 2014
Last Updated
August 7, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02059174
Brief Title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1293 Compared With a Basal Insulin in Participants With Type 1 Diabetes (MK-1293-005)
Official Title
A Single Dose Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-1293 and to Compare Its Pharmacologic Properties to Those of Another Basal Insulin in Subjects With Type I Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
February 10, 2014 (Actual)
Primary Completion Date
March 30, 2015 (Actual)
Study Completion Date
April 27, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the safety, pharmacokinetics, and pharmacodynamics of MK-1293 compared with a basal insulin (EU-Lantus™) in participants with Type 1 Diabetes. The primary hypotheses are that the duration of action, pharmacodynamic profile, and pharmacokinetic profile of MK-1293 and the comparator basal insulin are similar.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
76 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™
Arm Type
Experimental
Arm Description
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
Arm Title
EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293
Arm Type
Experimental
Arm Description
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
Intervention Type
Drug
Intervention Name(s)
MK-1293
Intervention Description
MK-1293 0.4 units/kg administered subcutaneously
Intervention Type
Drug
Intervention Name(s)
EU-Lantus™
Intervention Description
EU-Lantus™ 0.4 units/kg administered subcutaneously
Intervention Type
Drug
Intervention Name(s)
Novolog™
Intervention Description
Participants will receive an intravenous infusion of insulin aspart (Novolog™ or other rapid-acting insulin analog) for several hours prior to MK-1293 or EU-Lantus™ dosing in each dosing period to meet basal insulin requirements
Primary Outcome Measure Information:
Title
Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
Description
Duration of Action (DOA) is defined as the length of time from dosing to End of Action. End of Action is defined as the time point at which plasma glucose has been above 150 mg/dL for 30 minutes and no glucose has been infused for 30 minutes. Median and max below are reported for the length of clamp duration (i.e. 30 hours).
Time Frame
Up to 30 hours postdose
Title
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over 24 Hours After Dosing (GIR-AUC0-24hr)
Description
The area under the glucose infusion rate curve from hours 0 to 24 after injection (AUC[GIR{0-24}]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Time Frame
Up to 24 hours postdose
Title
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the First 12 Hours After Dosing (GIR-AUC0-12hr)
Description
The area under the glucose infusion rate curve from hours 0 to 12 after injection (AUC[GIR{0-12}]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Time Frame
Up to 12 hours postdose
Title
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the Second 12 Hours After Dosing (GIR-AUC12-24hr)
Description
The area under the glucose infusion rate curve from hours 12 to 24 after injection (AUC[GIR{12-24}]) for participants who received either MK-1293 or Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Time Frame
From 12 to 24 hours postdose
Title
PD: Maximum Glucose Infusion Rate (GIRmax)
Description
Maximum glucose infusion rate (GIR[max]) based on smoothed data for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Time Frame
Up to 30 hours postdose
Title
M1 Glargine Metabolite Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC0-24)
Description
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Analysis was performed on log scale with results back transformed to the original scale
Time Frame
Up to 24 hours postdose
Title
M1 Glargine Metabolite PK: Maximum Plasma Concentration (Cmax)
Description
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Analysis was performed on log scale with results back transformed to original scale.
Time Frame
Up to 24 hours postdose
Secondary Outcome Measure Information:
Title
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the First 12 Hours After Dosing (AUC0-12)
Description
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-12 is a measure of the total amount of drug in the plasma from the dose to Hour 12. Analysis was performed on log scale with results back transformed to original scale.
Time Frame
Up to 12 hours postdose
Title
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the Second 12 Hours After Dosing (AUC12-24)
Description
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC12-24 is a measure of the total amount of drug in the plasma from Hour 12 to Hour 24. Analysis was performed on log scale with results back transformed to original scale.
Time Frame
From 12 to 24 hours postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has type 1 diabetes mellitus diagnosed at least 12 months before screening
Subject to investigator discretion, is on a stable dose of insulin for at least 2 weeks before screening
Has a total daily insulin dose <=1.2 units/kg
Has a screening hemoglobin A1c <9.5%
Has a body mass index >18.0 and <=30.0 kg/m^2
Has a weight >=50 kg
Female participant of reproductive potential has a serum beta-human chorionic gonadotropin level consistent with the nongravid state and agrees to use (and/or have her partner use) 2 acceptable methods of birth control until 2 weeks after the last dose of study drug
Postmenopausal female participant is without menses for >=1 year
Surgically sterile female participant status is post hysterectomy, oophorectomy, or tubal ligation
Has not used nicotine or nicotine-containing products for at least 3 months before study start or smokes less than 10 cigarettes per day and is willing to abstain during the trial
Exclusion Criteria:
Has a history of clinically significant gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
Has a history of clinically significant endocrine abnormalities or diseases except type 1 diabetes mellitus
Has had any severe hypoglycemic episodes associated with hypoglycemic seizures, comas, or unconsciousness within the past 3 months
Has a history of diabetic ketoacidosis within the past 6 months
Has a history of significant multiple or severe allergies, anaphylactic reaction, or significant intolerability to drugs or food
Has a history of hypersensitivity to pharmacologic insulins
Is positive for hepatitis B surface antigen, hepatitis C, or Human Immunodeficiency Virus
Has had major surgery or donated or lost 1 unit of blood within 4 weeks before screening
Unable to refrain from use of any medication or herbal remedy from 2 weeks prior to the first dose of study drug to until the posttrial visit. Some medications are permitted and may be discussed with the investigators
Vaccination within 12 weeks of start of study participation
Consumes >3 glasses of alcoholic beverages per day. Participants consuming 4 glasses of alcoholic beverages may be enrolled at the discretion of the investigator.
Consumes >6 servings of caffeinated beverages per day
Is a regular user of any illicit drugs or has a history of drug abuse (including alcohol) within approximately 1 year
Is on a carbohydrate-restricted diet (<100 grams carbohydrate per day); participants who are on a carbohydrate-restricted diet may be included if they agree to a diet consisting of >=100 grams of carbohydrate daily throughout the study
Has a personal or family history of hypercoagulability or thromboembolic disease
Has used systemic glucocorticoids within 3 months of screening or anticipates treatment with systemic glucocorticoids during study participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
28817223
Citation
Crutchlow MF, Palcza JS, Mostoller KM, Mahon CD, Barbour AM, Marcos MC, Xu Y, Watkins E, Morrow L, Hompesch M. Single-dose euglycaemic clamp studies demonstrating pharmacokinetic and pharmacodynamic similarity between MK-1293 insulin glargine and originator insulin glargine (Lantus) in subjects with type 1 diabetes and healthy subjects. Diabetes Obes Metab. 2018 Feb;20(2):400-408. doi: 10.1111/dom.13084. Epub 2017 Sep 26.
Results Reference
result
Learn more about this trial
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1293 Compared With a Basal Insulin in Participants With Type 1 Diabetes (MK-1293-005)
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