Inhalation Device Allows Novel Administration of Apomorphine in Men with Erectile Dysfunction—Efficacy and Safety Findings

Abstract

Erectile dysfunction (ED) treatment is greatly influenced by patient preference, and currently available oral therapies do not meet all patients' needs. New therapies and formulations are therefore being investigated. The aim of this article is to assess the clinical efficacy and safety of inhaled apomorphine, VR004, in men with mild to severe ED. Efficacy outcomes were the change in the proportion of positive responses to sexual encounter profile questions, International Index of Erectile Function (IIEF) scores and onset of therapeutic effect. Safety outcomes included a change in vital signs at an orthostatic challenge and adverse events (AEs). Two consecutive, multicenter trials each comprised a 4-week no-treatment period and a 12-week "at home" treatment period with regular clinic visits. Patients (N = 211 and N = 389) were randomized to receive one of three set doses of VR004 (100-300 microg) or matching placebo in each trial. VR004 was administered by a dry-powder inhaler at least once a week. Efficacy was generally dose dependent. The proportion of per-protocol patients maintaining an erection long enough for successful intercourse increased in all VR004 groups vs. placebo. IIEF scores were higher in the VR004 groups compared with placebo, and the majority of responders achieved an erection within 10 minutes of dosing. The safety profile of VR004 was generally similar to that of placebo, and AEs were mild or moderate in severity. The incidence of treatment-related AEs was dose dependent. Few patients (4%) withdrew because of treatment-related AEs, and the majority of these withdrawals occurred on the day of the stringent orthostatic challenge. The VR004 system administers low apomorphine doses that are well tolerated without compromising efficacy. This route of administration ensures a rapid onset of action and reproducible efficacy and safety profiles. Inhaled apomorphine is therefore a potential first-line treatment for ED.