Initial safety, tolerability, pharmacodynamics, and pharmacokinetics of Cl-1007 in patients with schizophrenia

CI-1007 is a novel dopamine autoreceptor agonist and partial dopamine D-2/D -3 agonist that is currently under development for the treatment of schizop hrenia. This single-blind, rising, multiple-dose, inpatient bridging study was designed to evaluate the safety and tolerability of CI-1007 in consecut ive panels of patients with schizophrenia. Following a 4-day placebo washou t period, 16 patients (4 per panel) were assigned to receive one of four fi xed-dosage regimens of CI-1007 (5, 10, 15, or 20 mg q12h for 9 doses). CI-1 007 was generally well tolerated over the dose range evaluated. Adverse eve nts, including mild to moderate sporadic orthostatic hypotension and/or nau sea and vomiting, were most commonly observed after the initial drug dose a nd decreased after repeated dosing. Serum concentrations of growth hormone (GH) increased following the administration of CI-1007, confirming its cent ral dopamine agonist activity. Changes in serum prolactin were not related to dose. The pharmacokinetics of CI-1007 and its active metabolite appear l inearly related to dose. The results of this study suggest that patients wi th schizophrenia tolerate slightly higher initial doses of CI-1007 than do healthy subjects.