Clinical trial NCT02059174: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-02-11
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
timeFrame: Up to 30 hours postdose
measure: PD: Area Under the Glucose Infusion Rate Versus Time Curve Over 24 Hours After Dosing (GIR-AUC0-24hr)
timeFrame: Up to 24 hours postdose
measure: PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the First 12 Hours After Dosing (GIR-AUC0-12hr)
timeFrame: Up to 12 hours postdose
measure: PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the Second 12 Hours After Dosing (GIR-AUC12-24hr)
timeFrame: From 12 to 24 hours postdose
measure: PD: Maximum Glucose Infusion Rate (GIRmax)
timeFrame: Up to 30 hours postdose
measure: M1 Glargine Metabolite Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC0-24)
timeFrame: Up to 24 hours postdose
measure: M1 Glargine Metabolite PK: Maximum Plasma Concentration (Cmax)
timeFrame: Up to 24 hours postdose
Secondary outcomes:
measure: M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the First 12 Hours After Dosing (AUC0-12)
timeFrame: Up to 12 hours postdose
measure: M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the Second 12 Hours After Dosing (AUC12-24)
timeFrame: From 12 to 24 hours postdose
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.