Abstract | BACKGROUND: 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 AUC(24) 1.27 ng x h/mL and 4.05 ng x 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.
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Authors | Ravi Anand, Michael Seiberling, Thierry Kamtchoua, Rolf Pokorny |
Journal | Clinical pharmacokinetics
(Clin Pharmacokinet)
Vol. 46
Issue 4
Pg. 351-8
( 2007)
ISSN: 0312-5963 [Print] Switzerland |
PMID | 17375985
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- FGLL peptide
- Neural Cell Adhesion Molecules
- Peptides
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Topics |
- Administration, Intranasal
- Adult
- Area Under Curve
- Dose-Response Relationship, Drug
- Drug Delivery Systems
- Electrocardiography
(drug effects)
- Humans
- Male
- Middle Aged
- Neural Cell Adhesion Molecules
(administration & dosage, adverse effects, pharmacokinetics)
- Peptides
(administration & dosage, adverse effects, pharmacokinetics)
- Radioimmunoassay
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