Published in:
01-04-2007 | Original Research Article
Tolerability, Safety and Pharmacokinetics of the FGLL Peptide, a Novel Mimetic of Neural Cell Adhesion Molecule, Following Intranasal Administration in Healthy Volunteers
Authors:
Ravi Anand, MD, Michael Seiberling, Thierry Kamtchoua, Rolf Pokorny
Published in:
Clinical Pharmacokinetics
|
Issue 4/2007
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Abstract
Background
The FG loop peptide (FGLL), 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 FGLL, with no systemic toxicity. This article reports on the results of the first administration of FGLL in humans.
Objective
To determine the tolerability, safety and pharmacokinetics of ascending, single intranasal doses of FGLL 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 FGLL (25, 100 and 200mg) in accordance with an ascending dose, sequential-cohort design.
Results
All three intranasal doses of FGLL 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 FGLL 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 FGLL; no relationship to the study drug was suspected. Quantifiable plasma concentrations of FGLL were observed up to 1 hour after intranasal administration of the 100mg dose and up to 4 hours after the 200mg dose (plasma FGLL concentrations were undetectable at all timepoints for the 25mg dose). Increasing doses of FGLL were associated with higher systemic exposures: mean Cmax 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 FGLL (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 FGLL in patients with Alzheimer’s disease.