Single-dose pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 in healthy subjects

LY2605541 is a novel basal insulin analog with a prolonged duration of action. Two Phase I studies assessed LY2605541 pharmacokinetics (PK), glucodynamics (GD), and tolerability in healthy subjects. In Study 1, 33 subjects received single subcutaneous (SC) doses of LY2605541 (0.01–2.22 U/kg) and ins...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of clinical pharmacology Vol. 54; no. 7; pp. 792 - 799
Main Authors:	Sinha, Vikram P., Choi, Siak Leng, Soon, Danny Kwang Wei, Mace, Kenneth F., Yeo, Kwee Poo, Lim, Shufen T. H., Howey, Daniel C.
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-07-2014 American College of Clinical Pharmacology Wiley Subscription Services, Inc
Subjects:	Adult Biological Availability Blood Glucose - analysis Cohort Studies Cross-Over Studies Dose-Response Relationship, Drug Drugs, Investigational - administration & dosage Drugs, Investigational - adverse effects Drugs, Investigational - analysis Drugs, Investigational - pharmacokinetics Female glucodynamics Glucose Clamp Technique Half-Life Humans Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - adverse effects Hypoglycemic Agents - blood Hypoglycemic Agents - pharmacokinetics Infusions, Intravenous Injections, Subcutaneous Insulin Insulin Glargine Insulin Lispro - administration & dosage Insulin Lispro - adverse effects Insulin Lispro - blood Insulin Lispro - pharmacokinetics Insulin, Long-Acting - administration & dosage Insulin, Long-Acting - adverse effects Insulin, Long-Acting - blood Insulin, Long-Acting - pharmacokinetics long-acting basal insulin Male Metabolic Clearance Rate Middle Aged pharmacokinetics Polyethylene Glycols - administration & dosage Polyethylene Glycols - adverse effects Polyethylene Glycols - pharmacokinetics Reproducibility of Results Young Adult glucodynamics pharmacokinetics long-acting basal insulin
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	LY2605541 is a novel basal insulin analog with a prolonged duration of action. Two Phase I studies assessed LY2605541 pharmacokinetics (PK), glucodynamics (GD), and tolerability in healthy subjects. In Study 1, 33 subjects received single subcutaneous (SC) doses of LY2605541 (0.01–2.22 U/kg) and insulin glargine (0.5–0.8 U/kg) followed by euglycemic clamp for up to 24–36 hours. In Study 2, absolute bioavailability of SC LY2605541 was assessed in 8 subjects by comparing dose normalized area under concentration versus time curve of SC against IV administration. Time‐to‐maximum plasma concentration (medians) and geometric means for half‐life (t1/2) and apparent clearance, respectively, ranged from 18.0 to 42.0 hours, 24.4–45.5 hours, and 1.8–2.8 L/h for SC LY2605541, versus 10.0–12.0 hours, 12.2–14.9 hours, and 51.4–65.2 L/h for SC insulin glargine. LY2605541 glucose infusion rate (GIR) profiles were sustained for ≥36 hours versus glargine GIR profiles, which waned at 24 hours. After IV administration, LY2605541's geometric mean t1/2 was 2.3 hours. LY2605541 intra‐subject variability (CV%) was <18% for PK and <32% for GD parameters. The most common adverse events were related to study procedures and were mild‐moderate in severity. These results established a well‐tolerated baseline dose for LY2605541 with a relatively flat PK profile and low intra‐subject variability.
Bibliography:	ArticleID:JCPH276 istex:A5A128B4C8BFF29AA181F9AC0D8EBA04415A7EDE ark:/67375/WNG-XCM34BS4-9 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23
ISSN:	0091-2700 1552-4604
DOI:	10.1002/jcph.276