A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression

Background: INN 00835 is a synthetic pentapeptide with a potential for rapi d onset of action as an antidepressant. Its efficacy was investigated in a pilot study in patients diagnosed with major depression. Methods: Fifty two patients received either active drug - INN 00835 (26 patients) - or placeb o (26 patients), subcutaneously at 0.2 mg/kg for 5 consecutive days. The pa tients were evaluated for an additional 4 weeks after treatment. Efficacy w as evaluated by the following psychiatric rating scales: HAMD, MADRS, CSRS, CGI, and VAS. The effect of treatment was also evaluated by using a bioche mical marker: changes in blood platelet serotonin (5HT) uptake rates in dru g-treated patients compared to those in the placebo group. Plasma concentra tions of INN 00835 were measured by LC/MS. Results: Statistical analysis in dicated a strong pharmacodynamic correlation between plasma drug concentrat ions at 1 h after dosing and the reduction in the severity of depression as measured by the psychiatric rating scales. A minimum effective plasma conc entration (MEC) of INN 00835 was 5 ng/ml. Statistically significant differe nces in response to treatment (P < 0.05) were found between patients with p lasma concentrations above MEC and those in the placebo group, as well as b etween subjects with plasma concentrations above and below the MEG. The pea k effect was observed after the 5-day treatment and the response to treatme nt persisted during the 4-week follow-up period. The change of 5HT uptake r ates after treatment was significantly larger in the drug-treated group tha n in the placebo group. Limitations: This was a pilot study conducted in a relatively small population (52 patients) and the limited number of blood s ampling times did not allow a comprehensive pharmacokinetic analysis. There was a relatively large placebo response. The results have to be confirmed in future, large scale studies. Conclusions: INN 00835 appears to be a prom ising drug for the treatment of major depression. (C) 2000 Elsevier Science B.V. All rights reserved.