Single-dose, placebo-controlled, phase I study of oral dolasetron

To evaluate the safety, tolerability, and pharmacokinetics of single, escalating doses of oral dolasetron mesylate, a new 5-HT3 receptor antagonist.

Double-blind, placebo-controlled, dose-escalating phase I study.

A clinical research center.

One hundred twenty healthy male volunteers.

Subjects received either placebo or oral dolasetron mesylate 50, 100, 150, 200, 250, 300, or 400 mg.

Compared with placebo, subjects receiving dolasetron mesylate reported a greater frequency of headache, light-headedness, dizziness, increased appetite, and nausea. There were no clinically significant changes in mean laboratory values from before to after treatment. Adverse events were transient, mild or moderate, and similar to those after single intravenous doses of the drug. No clinically significant electrocardiographic changes occurred, but lengthening of the QRS complex duration and dose-dependent lengthening of PR and QTc intervals were observed 1-2 hours after dosing. These effects were asymptomatic and were mainly associated with higher doses (< or = 300 mg).

Dolasetron mesylate is well tolerated when administered in single oral doses up to 400 mg to healthy volunteers. Clinical trials are under way to evaluate the agent's efficacy in preventing chemotherapy-induced and postoperative nausea and vomiting with doses up to 200 mg.