An open-label, uncontrolled dose-optimization study of sublingual apomorphine in erectile dysfunction

Background: Because apomorphine is a dopamine agonist that acts on areas of the central nervous system believed to mediate penile erection, its use in erectile dysfunction (ED) has been investigated. However. it also produces nausea by dopamine-receptor stimulation of the chemotrigger zone in the br ain. Therefore, a low plasma concentration, achieved rapidly, would be sele ctive for the desired erectile response but would be below the dopamine thr eshold for nausea. Objective: We evaluated the efficacy and tolerability of a dose-optimized r egimen of a sublingual formulation of apomorphine (apomorphine SL) in the t reatment of ED. Methods: This was a multicenter, open-label, uncontrolled, Phase III dose-o ptimization study of apomorphine SL in heterosexual men with ED. The 2-week screening period, during which baseline severity of ED was determined usin g the International Index of Erectile Function, was followed by a 3-week do se-optimization period beginning at a dose of 2 mg. Patients were to make a t least 2 attempts at intercourse per week throughout the study, placing 1 apomorphine tablet under the tongue beforehand. At the end of the first wee k. the dose could be increased to 3 mg at the discretion of the investigato r, at the end of the second week, the dose could be increased to a maximum of 4 mg or decreased as needed. In the following 4-week treatment period, p atients took their individual optimal doses. The primary efficacy variable was the percentage of attempts resulting in erections firm enough for inter course, as assessed by investigators' review of data from patients' diaries . Secondary variables included the percentage of attempts resulting in succ essful intercourse, time to erection, and duration of erection. Information about adverse events, including their severity and relation to treatment. was determined on the basis of direct questioning, spontaneous reports, and review of patient diaries. Results: The study enrolled 849 heterosexual men whose ages ranged from 31 to 78 years (mean, 58.1 years). They had a mean 5.7-year history of ED of v arious causes. ED was mild in 11.5% of the men, moderate in 23.8%. and seve re in 48.1%. When results of the last 8 attempts were pooled, representing the period during which patients were taking their optimal doses of apomorp hine SL, the mean percentage of attempts resulting in erections firm enough for intercourse was 39.4%, compared with 13.1% at baseline;, attempts resu lting in intercourse increased from a mean of 12.7% at baseline to 38.3% wi th treatment. The average median time to erection was 23 minutes, and the a verage median duration of erection was 13 minutes. Nausea, the most common treatment-related adverse event (11.7%), was dose related and diminished wi th continued dosing. One patient had a single syncopal episode that was jud ged to be related to apomorphine SL. Conclusions: In the present study, a dose-optimization regimen of apomorphi ne SL-with dosing initiated at 2 mg and adjusted up to a maximum of 4 mg as needed-was effective and well tolerated in the treatment of ED, regardless of its cause or severity.