Combination therapy for erectile dysfunction: a randomized, double blind, unblinded active-controlled, cross-over study of the pharmacodynamics and safety of combined oral formulations of apomorphine hydrochloride, phentolamine mesylate and papaverine hydrochloride in men with moderate to severe erectile dysfunction

Abstract

Combination therapy for erectile dysfunction: a randomized, double blind, unblinded active-controlled, cross-over study of the pharmacodynamics and safety of combined oral formulations of apomorphine hydrochloride, phentolamine mesylate and papaverine hydrochloride in men with moderate to severe erectile dysfunction Oral therapy has become first line treatment for patients with mild to moderate erectile dysfunction (ED). Studies have shown that sildenafil may not be effective in all patients, and has been associated with a variety of adverse effects and an adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes. The objective was to compare the efficacy and safety of three different oral combinations with the highest dose of sildenafil in men with moderate to severe ED. Randomized, double blind, unblinded active-controlled, Phase II study was carried out at three sites in Mexico. After a 4-week placebo run-in period, patients received all four of the following treatments using a 4-way cross-over design: 40 mg phentolamine (PM) þ 6 mg apomorphine (Apo); 40 mg PM þ 150 mg papaverine (Pap); 40 mg PM þ 6 mg Apo þ 150 mg Pap (Tricombo); 100 mg sildenafil (SC). With the exception of sildenafil tablets, all study medication was blinded. Moderate to severe ED was defined as a less than 50% vaginal penetration success rate during the placebo run-in period. A total of 44 patients were enrolled, of whom 36 completed all four treatment periods. All treatments produced a significant effect in primary efficacy variable (Sexual Encounter Profile) compared to baseline, however, no statistically significant differences were found between treatments. A significant period effect was observed. Also, the four treatments were found not to differ significantly in five out of six secondary efficacy variables. The lowest incidence of treatment-related adverse events (AE) occurred in the 40 mg PM þ 6 mg Apo group (9.8%), followed by 100 mg SC (15%), and the other two combinations (16.7 and 17.5%, respectively). Nasocongestion and headache were the most frequently reported AE. An oral combination of vasoactive agents may provide an alternative approach to sildenafil. Based on these results a combination of phentolamine and apomorphine warrants further clinical investigation.

Men with Mild Erectile Dysfunction Benefit from Sildenafil Treatment

“…A limitation of the trial is that the analog scale, the event log questions (other than the EHS), and the GEQs have not been validated. However, as mentioned earlier, 2 of the event log questions are almost identical to questions of the SEP, which is also unvalidated but has been widely used in the assessment of treatment efficacy in men with ED since 2002 [37]. Also the pattern of results for the unvalidated outcomes of the current trial was similar to that of the validated outcomes.…”

Centrally acting drugs for erectile dysfunction: Do they have a future?

“…In a semiblinded study of 44 patients with ED, no differences in efficacy (Sexual Encounter Profile) were noted between various combinations of oral therapies, but a lowest incidence of adverse events were noted for apomorphine in combination with phentolamine [55].…”

Sildenafil citrate efficacy 8 h postdose in men with mild to moderate erectile dysfunction

“…An event log that included the Sexual Encounter Profile (SEP) 14 and the validated Erection Hardness Score (EHS) 15 was completed after each sexual encounter. SEP questions are SEP1 ('Were you able to achieve at least some erection (some enlargement of the penis)?…”