An evaluation of single dose administration of ALX-0600, a GLP-2 analog, in healthy male subjects

ALX-0600 is an analog of the human intestinal peptide, glucagon-like peptide-2 (GLP2), which is thought to be an important regulator of intestinal epithelial cell proliferation.ALX-0600 is being investigated for the treatment of malabsorption disorders resulting from Short Bowel Syndrome (SBS), Inflammatory Bowel Disease, chemotherapy, or radiation therapy.This study investigated the safety, tolerability, and pharmacokinetics of ALX -0600 after a single subcutaneous injection in healthy male volunteers.Thirty-two subjects (aged 18 to 45 years) were randomized to four dose groups, with six volunteers receiving ALX-0600 and two volunteers receiving placebo in each dose group in a blinded fashion.Doses of 2.5, 5.0, 7.0, and 10.0 mg were administered in ascending order.ALX-0600 was well tolerated.There were no clinically significant drugrelated changes in vital signs, 12-lead ECG, clinical laboratory evaluations, body weight, or physical examination.A total of 23 treatment emergent adverse events were identified among 13 of 24 volunteers who received ALX-0600 or placebo.Six of these adverse events, all of which were mild in severity, were deemed related to study-drug by the investigator and occurred at the 7.0 and 10.0 mg doses.Five were related to the injection site: pain (n =3), and reactions of pruritus and erythema (n=2).One subject developed a rash on his upper body.Four episodes of headache were reported in three subjects and may have occurred as a result of the subjects fasted state.Following subcutaneous administration, the mean peak plasma concentration of ALX-0600 ranged from 27 ng/mL for the 2.5 mg dose to 101 ng/mL for the 10 mg dose.Median peak plasma concentrations were achieved at 3 hours post-injection.The increases in peak and total systemic drug exposure were proportional to the increase in dose.There were insufficient timepoints to accurately estimate pharmacokinetic parameters for the elimination phase of ALX-0600.In conclusion, ALX-0600 was safe and well tolerated up to and including a dose of 10 mg when administered by single subcutaneous injection to healthy male subjects.4974