A Double-Blind, Placebo-Controlled, Ascending-Dose, Randomized Study to Evaluate the Safety, Tolerability and Effects on Cognition of AL-108 after 12 Weeks of Intranasal Administration in Subjects with Mild Cognitive Impairment

• Published in: Dementia and geriatric cognitive disorders Vol. 35; no. 5-6; pp. 325 - 339
• Main Authors: Morimoto, Bruce H., Schmechel, Don, Hirman, Joe, Blackwell, Andrew, Keith, Julian, Gold, Michael
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.05.2013; S. Karger AG
• Subjects: Administration, Intranasal; Aged; Aged, 80 and over; Biological and medical sciences; Cognition - drug effects; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - psychology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Medical sciences; Memory, Short-Term - drug effects; Middle Aged; Neurology; Neuropsychological Tests; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Oligopeptides - therapeutic use; Original Research Article; Paired-Associate Learning - drug effects; Patient Compliance; Space Perception - drug effects; Vascular diseases and vascular malformations of the nervous system; Drug candidate AL-108; Neuroprotection; Mild cognitive impairment; Intranasal dosing; Davunetide; Dementia; Human; Blind; Nervous system diseases; Cognitive disorder; Cognition; Intranasal administration; mild cognitive impairment; Degenerative disease
• ISSN: 1420-8008; 1421-9824; 1421-9824
• DOI: 10.1159/000348347

Background/Aims: AL-108-211 was a placebo-controlled, ascending-dose study that explored the safety, tolerability and efficacy of 12 weeks of treatment with AL-108 in subjects with amnestic mild cognitive impairment. Methods: A total of 144 subjects were randomized in a 2:1 drug:placebo ratio. Subjects were enrolled into the low-dose group or placebo and then to the high-dose group or placebo. Pooling of the placebo groups yielded 3 groups (approx. 48/group) whose baseline demographics and disease characteristics were well matched. Results: AL-108 was generally safe and well tolerated. Analyses of efficacy data failed to detect a statistically significant difference between the treatment groups on the composite cognitive memory score. Analyses of the individual cognitive tasks identified signals of potential efficacy in 2 tests of memory and attention. Conclusion: These data suggest that AL-108 was generally safe, well tolerated and merits additional investigation as a treatment for Alzheimer's disease.