Authors: Anand, Ravi¹; Seiberling, Michael²; Kamtchoua, Thierry²; Pokorny, Rolf²

Source: Clinical Pharmacokinetics, Volume 46, Number 4, 2007 , pp. 351-358(8)

Publisher: Adis International

Abstract:

Background: The FG loop peptide (FGL_L), a novel mimetic of the neural cell adhesion molecule (NCAM), is in clinical development for neurodegenerative disorders such as Alzheimer's disease. Preclinical studies in rats, dogs and monkeys have demonstrated exposure in plasma and cerebrospinal fluid after parenteral or intranasal administration of FGL_L, with no systemic toxicity. This article reports on the results of the first administration of FGL_L in humans.

Objective: To determine the tolerability, safety and pharmacokinetics of ascending, single intranasal doses of FGL_L 25, 100 and 200mg in healthy subjects.

Methods: In an 8-day, open-label, phase I study, 24 healthy male volunteers (mean age 42 [range 24-55] years) received single intranasal doses of FGL_L (25, 100 and 200mg) in accordance with an ascending dose, sequential-cohort design.

Results: All three intranasal doses of FGL_L were well tolerated and there were no clinical notable abnormalities in ECG recordings, vital signs or laboratory tests. Three subjects (13%) reported five adverse events. A transient (<3 minutes) burning sensation in the nose was reported in two subjects at the 200mg dose level while runny eyes (<2 minutes) were experienced in one subject at 25mg. These events had an onset immediately following intranasal administration, and a relationship to FGL_L was suspected. One of the latter subjects who had experienced a burning sensation in the nose also experienced dizziness, vomiting and headache with onset >2 days after single-dose administration of FGL_L; no relationship to the study drug was suspected. Quantifiable plasma concentrations of FGL_L were observed up to 1 hour after intranasal administration of the 100mg dose and up to 4 hours after the 200mg dose (plasma FGL_L concentrations were undetectable at all timepoints for the 25mg dose). Increasing doses of FGL_L were associated with higher systemic exposures: mean C_max 0.52 ng/mL and 1.38 ng/mL (100mg and 200mg, respectively); mean AUC₂₄ 1.27 ng · h/mL and 4.05 ng · h/mL (100mg and 200mg, respectively).

Conclusions: Intranasal administration of FGL_L (25, 100 and 200mg) was well tolerated in healthy male volunteers, with no safety concerns and a pharmacokinetic profile that was generally dose related. Further studies are currently being planned to evaluate the effects of FGL_L in patients with Alzheimer's disease.

Keywords: Antidementias; FGLL; Research and development

Document Type: Research article

Affiliations: 1: 1 Anand Pharma Consulting, Oberwil, Switzerland 2: 2 Swiss Pharma Contract Ltd, Allschwil, Switzerland

Publication date: 2007-01-01

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