A DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING SAFETY EVALUATION OFSINGLE-DOSE INTRAVENOUS DOLASETRON IN HEALTHY MALE-VOLUNTEERS

The safety and tolerability of dolasetron mesylate, a potent and selec tive 5-HT3 receptor antagonist, were evaluated after single intravenou s doses in healthy male volunteers. In this double-blind, placebo-cont rolled, randomized, phase I study, 80 subjects received either placebo or dolasetron in escalating doses (0.6 to 5.0 mg/k). Subjects were mo nitored for adverse events, vital sign and laboratory alterations, and changes in electrocardiographic (EGG) intervals and electroencephalog raphic (EEG) patterns. Overall, the per centage of subjects reporting adverse events was similar in those receiving dolasetron (44/64; 68.8% ) or placebo (10/16; 62.5%); most adverse events were mild in severity . Subjects receiving dolasetron reported a higher incidence of central nervous system (headache and dizziness/lightheadedness), gastrointest inal (increased appetite and nausea), and visual adverse events and ta ste alterations. No clinically significant changes in laboratory varia bles were observed. Transient and asymptomatic ECG changes (small mean increases in PR interval and QRS complex duration versus baseline) we re noted in several subjects at 1 to 2 hours after infusion at doses g reater than or equal to 3.0 mg/kg. Transient, mild blood pressure decr eases were observed in five subjects, including one on placebo. Dolase tron mesylate was well tolerated in single intravenous doses up to 5.0 mg/kg in healthy male volunteers. Clinical studies of the drug are on going for antiemetic indications.