Abstract

Objective: The safety, tolerability, pharmacokinetics and preliminary pharmacodynamics of single rising doses of a novel GLP-1 analog, CJC-1131, was evaluated. Methods: CJC-1131 was subcutaneously injected in 8 groups (1.5 – 20.5 µg/kg) of healthy subjects (each group of six subjects included 1 placebo per dose level). CJC-1131 was also injected subcutaneously in 6 groups (1.5 – 12 µg/kg) of Type 2 diabetic patients after a 9-day washout period from their own anti-diabetic medication. Each group of 8 patients included 2 placebo-treated patients. Seven blood glucose measurements were taken daily, and meal tolerance tests were performed on the day before dosing and on Day 3. Results: CJC-1131 was quickly absorbed from the subcutaneous space, and a less than dose-proportional increase was found in C_max. The half-life of CJC-1131 varied from 8.9 – 14.7 days in healthy subjects and from 9.1 – 13.8 days in patients. The maximum tolerated dose in healthy subjects was established at 12 µg/kg with nausea and vomiting being the dose-limiting events. These events occurred generally in the morning after dosing. Blood glucose levels in patients decreased on Day 1 in proportion with dose, with a maximum average decrease of 4.1 mmol/l in the highest dose group. Higher doses appeared to be related to a slight weight loss in patients. Conclusions: Conjugation to albumin led to a major prolongation of the half-life of GLP-1. The tolerability of this potential antidiabetic drug seems to be limited only by gastrointestinal complaints.

Author Details

Authors

• R.G. Tiessen¹
• J.P. Castaigne²
• J.F. Dreyfus²
• M. Nemansky¹
• H.H. Kruizinga¹
• A.A. van Vliet¹

Departments

• ¹ PRA International, Zuidlaren, The Netherlands, and
• ² ConjuChem Inc. (CJC), Montreal, Canada

Address

R.G. Tiessen, PhD, MD; PRA International, P.O. Box 200, 9470 AE Zuidlaren, The Netherlands

Email: [email protected]

Citation