Effectiveness and safety of posatirelin in the treatment of senile dementia: A multicenter, double-blind, placebo-controlled study

Summary icenter, double-blind, placebo-controlled study was carried out in elderly demented patients in order to confirm the efficacy and safety of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having neurotrophic effects and modulatory activity on the monoaminergic and cholinergic systems. The experimental design consisted of a two-week run-in placebo phase, followed by a double-blind period of three months, with posatirelin (10 mg/ml) or placebo administered once daily intramuscularly. Gottfries-Brne-Steen (GBS) rating scale was utilized as the primary efficacy variable and was measured at start, after 45 and 90 days. For safety evaluation laboratory tests, vital signs and adverse events were monitored. Data were evaluated using analysis of variance on the per protocol (PP) and intent-to-treat (ITT) samples. From a total of 213 patients (mean ± SD age: 78.8 ± 6.2 years) 107 were randomly assigned to posatirelin, and 106 to placebo; because of 3 cases of protocol violations or 38 dropouts, 172 patients were considered available for the PP analysis. Significant differences were obtained in the posatirelin group when analyzing the summary measures (sum of differences from baseline) of the GBS total score both in explanatory (PP) (p = 0.009) and in pragmatic (ITT) (p < 0.001) approaches. No significant differences in blood pressure, heart rate or laboratory routine parameters were observed. Ten posatirelin patients (9.3 %) and four placebo patients (3.8 %) experienced non-serious adverse drug reactions; nausea, gastric pain, palpitation were the most frequent adverse drug reactions observed in the posatirelin group. These findings confirm previous results showing that posatirelin treatment can improve cognitive and functional abilities of elderly demented patients.