(191) A PHASE II REPEAT SINGLE ORAL DOSE STUDY OF IP2015 OR PLACEBO IN HEALTHY MALE SUBJECTS WITH ERECTILE DYSFUNCTION

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Abstract Introduction Treatment with phosphodiesterase type 5 inhibitors (PDE5i) has been successful in men with ED of vascular origin. Still, approximately 30 to 40% of men with erectile dysfunction (ED) do not respond to the PDE5i drug therapy, and this group of patients still experience low QoL. In addition, patients suffering from neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5i, or they may be contraindicated. The novel monoamine reuptake inhibitor, IP2015, induced erection by increasing central dopamine and peripheral nitric oxide in rodents and showed positive effects in a phase IIa erotic movie Rigiscan study. Objective The primary objective of the study was to investigate the effects of repeat single oral doses of IP2015 (pudafensine) on male subjects with ED on the ability to develop and maintain an erection. Methods The study was a multicenter, phase II, randomized, double-blind, parallel-group, placebo-controlled in healthy male subjects with erectile dysfunction. Men aged 18-65 years were screened, and after informed consent, those included with severe and moderate erectile dysfunction with a score < 16 in the 15-Question International Index of Erectile Function (IIEF 15) questionnaire. The subjects were randomized to 4-week treatment with a weekly dose of placebo, 5 mg, or 10 mg IP2015. The primary endpoint of the study was the change from baseline in responses to question 3 (Q3) and question 4 (Q4) in the IIEF 15 questionnaire at week 1 (day 1), week 2, week 3, week 4, and Follow-up in subjects administered IP2015 compared to placebo. The other questions in the IIEF-15 questionnaire, safety and plasma concentrations, were secondary endpoints. Analysis was performed by mixed model repeated measures (MMRM). Results The included subjects were in the placebo group (n = 45), 5 mg (n = 42), and 10 mg (n = 43) IP2015. The primary endpoint of the IIEF-15 Q3 score showed a statistically significant increase in the adjusted mean compared to baseline (P = 0.034) and placebo (P = 0.046) at week 3 and compared to baseline (P < 0.05) at the follow-up visits for the 5 mg IP2015 treatment group. For the 10 mg IP2015 and placebo treatment groups at all visits, overall, there was a decrease in adjusted mean scores compared to baseline. For the primary endpoint of the IIEF-15 Q4 score, there was a statistically significant increase in the adjusted mean compared to baseline (P = 0.0096) at the follow-up visit for the 5 mg IPED2015 treatment group. However, this increase was not statistically significant compared to placebo. Concerning the secondary IIEF-15 endpoints, there were positive tendencies for the treatment with the 5 mg IP2015. Treatment-emergent adverse effects (TEAEs) for 5 mg IP2015 were comparable to the placebo group. The TEAEs were headache, dizziness, and nausea; they were dose-dependent, mild, and moderate. There is a linear relation between plasma concentrations and the dose of IP2015. Conclusions The present study shows significant effects of IP2015 in patients with severe and moderate erectile dysfunction. The efficacy of the low dose and TEAEs at the placebo level suggests IP2015 can be used in patients with ED where PDE5 inhibition is insufficient. Disclosure Yes, this is sponsored by industry/sponsor: Initiator Pharma A/S. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Initiator Pharma A/S.

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