Pharmacodynamic and Pharmacokinetic Variability of a Basal Insulin (0000-168)

A Two-Part Clinical Trial to Assess Pharmacodynamic and Pharmacokinetic Variability of a Basal Insulin

The purpose of this study is to evaluate whether the within-subject variation in duration of action and time-action profile of glargine measured by isoglycemic clamp will be below prespecified levels.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: Isoglycemic Clamp; Drug: Comparator: insulin glargine

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Part 1:

• Patient is a male between 18 to 45 years of age (inclusive) at the prestudy (screening) visit
• Patient has a clinical diagnosis of type 1 diabetes
• Patient must have been treated with insulin since diagnosis and be on a stable dose of insulin
• Patient has a Body Mass Index (BMI) of <=27 kg/m2 and >18 kg/m2
• Patient has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months

Part 2:

• Subject is a male between 18 to 45 years of age at the prestudy (screening) visit
• Subject has a Body Mass Index (BMI) of <=25 kg/m^2
• Subject has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months

Exclusion Criteria:

Part 1:

• Patient has a history of stroke, chronic seizures, or major neurological disorder
• Patient has currently active and untreated clinically significant endocrine, cardiovascular, hematological, hepatic, renal, respiratory, or genitourinary abnormalities or diseases
• Patient has a history of hypertension requiring treatment
• Patient has a history of neoplastic disease within the past 5 years
• Patient is currently being treated with, or has a history of treatment with any oral antihyperglycemic agent
• Patient has a history of significant multiple and/or severe allergies

Part 2:

• Subject has a history of stroke, chronic seizures, or major neurological disorder
• Subject has a history of hypertension requiring treatment
• Subject has a history of neoplastic disease within the past 5 years
• Subject has history of diabetes (Type 1, Type 2 or steroid-induced) or family history of diabetes mellitus
• Subject has a history of hypersensitivity to glargine or any of its inactive ingredients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part 1; Part I of the trial	Drug: Isoglycemic Clamp; Isoglycemic Clamp, a procedure that includes IV infusion of short-acting Insulin (Part I) and glucose (Part I and 2); Drug: Comparator: insulin glargine; Insulin glargine at 0.4 U/kg; Other Names: LANTUS
Active Comparator: Part 2; Part II of the trial	Drug: Isoglycemic Clamp; Isoglycemic Clamp, a procedure that includes IV infusion of short-acting Insulin (Part I) and glucose (Part I and 2); Drug: Comparator: insulin glargine; Insulin glargine at 0.4 U/kg; Other Names: LANTUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part I: The within-subject standard deviation in duration of action of glargine (the difference between onset of action and end of action)	Baseline and 30 hours
Part II: The within-subject coefficient of variation in time-action profile of glargine for AUC-GIR (AUC of glucose infusion rate), GIRmax (maximum level of glucose infusion rate), over the duration of action of glargine	Baseline and 30 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Part I: The within-subject coefficient of variation in time-action profile of glargine for AUC-GIR and GIRmax over the duration of action of glargine	Baseline and 30 hours
Part II: The within-subject standard deviation in duration of action of glargine (the difference between onset of action and end of action)	Baseline and 30 hours

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: June 25, 2010
• First Submitted That Met QC Criteria: June 25, 2010
• First Posted (Estimate): June 29, 2010

Study Record Updates

• Last Update Posted (Estimate): July 23, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Insulin
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Glargine
• Other Study ID Numbers: 0000-168; 2010_541 (Other Identifier: Merck)