Lexicon Initiates Trial Of LX6171 Drug Candidate For Cognitive Disorders
Lexicon Pharmaceuticals commenced dosing in a Phase 2a clinical trial with LX6171, an oral drug candidate for the treatment of cognitive impairment associated with disorders such as Alzheimer's disease, schizophrenia, and vascular dementia. The initial stage of the trial will assess the bioavailability of a new oral-suspension formulation in healthy elderly subjects with a second stage evaluating safety, tolerability and cognitive effects in elderly subjects with age-associated memory impairment (AAMI).
"AAMI is an emerging area of clinical research and offers an expedient population for obtaining proof-of-concept with a drug candidate, like LX6171, that has a broad range of potential applications in the area of cognitive disorders," said Philip M. Brown, M.D., J.D., vice president of clinical development at Lexicon. "Following the strength of the Phase 1 data indicating LX6171 is generally well tolerated, we have adopted a two-stage strategy for Phase 2a in order to transition to our new oral suspension formulation and to assess for improvements in a variety of cognitive dimensions as we enter the elderly population."
Phase 2 Study Design
The initial stage of the trial will assess the bioavailability of a single-dose oral suspension in 16 healthy elderly subjects. The second stage will be a randomized, double-blind, placebo-controlled evaluation of safety, tolerability, and cognitive effects in approximately 120 subjects over four weeks. This stage is anticipated to include three groups of 40 subjects each, exploring two dose levels with a placebo control. Exact dose levels for the second stage will be set based on evaluation from the first stage pharmacokinetic study using the new formulation. The second stage will evaluate the safety and tolerability of LX6171 oral suspension in subjects exhibiting AAMI and will measure the cognitive effects of LX6171 in these subjects using the Cognitive Drug Research battery, along with other psychometric instruments. The study is being conducted in Europe, with initial results expected by the end of 2008.
LX6171 is an orally-bioavailable small molecule developed by Lexicon scientists to inhibit a membrane protein expressed exclusively in the central nervous system and found at synaptic vesicles and presynaptic membranes of glutamatergic neurons. The protein targeted by LX6171 was identified through Lexicon's large-scale gene knockout program, the Genome5000(TM). Knockout mice lacking this protein showed improved learning and memory compared with controls. In preclinical studies, administration of LX6171 resulted in improved performance in tests of learning and memory in mice. In Phase 1 clinical trials, LX6171 was generally well tolerated at all dose levels and showed good systemic exposure.