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)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: MK-1293; Drug: EU-Lantus™; Drug: Novolog™

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™; 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	Drug: MK-1293; MK-1293 0.4 units/kg administered subcutaneously; Drug: EU-Lantus™; EU-Lantus™ 0.4 units/kg administered subcutaneously; Drug: Novolog™; 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
Experimental: EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293; 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	Drug: MK-1293; MK-1293 0.4 units/kg administered subcutaneously; Drug: EU-Lantus™; EU-Lantus™ 0.4 units/kg administered subcutaneously; Drug: Novolog™; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Up to 30 hours postdose
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.	Up to 24 hours postdose
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.	Up to 12 hours postdose
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.	From 12 to 24 hours postdose
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.	Up to 30 hours postdose
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	Up to 24 hours postdose
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.	Up to 24 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 12 hours postdose
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.	From 12 to 24 hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2014
• Primary Completion (Actual): March 30, 2015
• Study Completion (Actual): April 27, 2015

Study Registration Dates

• First Submitted: February 7, 2014
• First Submitted That Met QC Criteria: February 7, 2014
• First Posted (Estimate): February 11, 2014

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Insulin Aspart; MK-1293
• Other Study ID Numbers: 1293-005; 2012-005656-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf