Intra-Cellular Therapies announced the initiation of ITI-007-200, a Phase I/II clinical trial designed to evaluate the safety, tolerability and pharmacokinetics of low doses of its lead drug candidate, ITI-007, in healthy geriatric subjects and in patients with dementia, including Alzheimer’s disease. According to a company release, the commencement of this study marks an important milestone in the strategy to develop low doses of ITI-007 for the treatment of behavioural disturbances associated with dementia and related disorders.
The ITI-007-200 trial is planned to be conducted in two parts. Part 1 is a randomised, double-blind, placebo-controlled multiple ascending dose evaluation of ITI-007 in healthy geriatric subjects. In each cohort in Part 1, it is anticipated that 10 subjects will be randomised to receive ITI-007 (N=8) or placebo (N=2) for seven days. In Part 2, it is anticipated that 12 patients with dementia will be randomised to receive ITI-007 (N=9) or placebo (N=3) for seven days. The number of cohorts in each part may be adjusted based on results. Safety, tolerability and pharmacokinetic data will be determined. Exploratory pharmacodynamic endpoints will be included to assess feasibility of measuring agitation, sedation, sleep and cognition in potential future trials. It is expected that initial data from the trial will be available in the second half of 2014.
The press release reports that in pre-clinical and clinical trials to date, ITI-007 combines potent serotonin 5-HT2A receptor antagonism, dopamine receptor phosphoprotein modulation, glutamatergic modulation and serotonin reuptake inhibition into a single drug candidate. At dopamine D2 receptors, ITI-007 has been demonstrated to have dual properties and to act as both a post-synaptic antagonist and a pre-synaptic partial agonist. ITI-007 has also been demonstrated to stimulate phosphorylation of glutamatergic NMDA NR2B, or GluN2B, receptors in a mesolimbic specific manner.