madman
Super Moderator
ABSTRACT
Introduction: The incidence of erectile dysfunction (ED) increases with age in mainland China and phosphodiesterase 5 inhibitors (PDE5i) are the major drugs used for its treatment.
Aim: To determine the efficacy and safety of Chinese developed avanafil as therapy for ED in China.
Methods: This phase III trial was carried out in 7 medical centers in China. Eligible subjects suffering from ED were allocated randomly into 3 groups (ratio 1:1:1) and orally received a placebo, 100 or 200 mg avanafil for a total of 12 weeks.
Main outcome measures: The primary endpoint was changed in erectile function (EF) domain scores according to the International Index of EF (IIEF) questionnaire from baseline to week 12 of therapy. Secondary endpoint assessments were changes in the response rates of SEP, Q2, and Q3; changes in IIEF other domain scores. Safety evaluation monitored treatment-emergent adverse events (TEAEs), serious TEAEs, laboratory test results, vital signs, and electrocardiographs.
Results: Of 218 randomized ED subjects, 182 (83.5%) completed the study. After 12-week therapy, alterations from baseline of the mean IIEF-EF domain scores in the 100 mg and 200 mg groups were greater than for the placebo (all P < .05) group. The changes in mean SEP Q2 response rates from baseline to week 12 in the placebo, 100 mg, and 200 mg groups were 5.4%, 22.3%, and 22.1%, and SEP Q3 response rates were 22.7%, 42.6%, and 38.1%, respectively. Avanafil treatment (regardless of dose) improved EF vs placebo for most of the other secondary efficacy endpoints studied (all P < .05). No differences were detected in efficacy endpoints between the 100 and 200 mg dosage groups (all P > .05) or in the incidence of TEAEs and drug-related TEAEs among the 3 groups (all P > .05).
Conclusion: Avanafil (100 or 200 mg) was effective and generally well-tolerated in Chinese subjects with ED.
INTRODUCTION
Erectile dysfunction (ED) has been characterized as “a persistent or repeated inability to achieve or maintain an adequate penile erection in order to facilitate a satisfactory sexual performance”.[1] The incidence of ED increases with age in mainland China from 20.86% of subjects <30 years old to 93.72% of those >70 years old.[2] Systemic diseases, trauma, and surgery, as well as medication, are closely associated with ED, but they can also be of psychogenic origin. The most common specific physical causes are atherosclerosis, diabetes, and complications following prostate surgery.[3-5]
Currently, phosphodiesterase 5 inhibitors (PDE5i) are administered orally as the initial treatment for ED.[6] Oral PDE5i can inhibit the degradation of cGMP and the elevated cyclic guanosine monophosphate (cGMP) concentration increases the blood volume of the penis and amplifies the neurological signal of erection, thus effectively treating ED.[7] Other treatments include vacuum erection devices,[8] intracavernosal injection of vasoactive substances,[9] low-intensity extracorporeal shock wave therapy,[10] and penile prosthesis surgery.[11]
At present, 3 PDE5i have been approved for sale in China, namely sildenafil, tadalafil, and vardenafil. Avanafil (Stendra) was initially approved by the FDA in the US and was shown to be effective and safe for ED therapy.[12,13] Avanafil is rapidly absorbed after oral administration and the maximum plasma concentration (Cmax) is achieved at a median time to reach Cmax (Tmax) of 30−45 minutes with a relatively short plasma half-life time (3−5 hours).[14] In addition, avanafil has also been shown to be effective in ED subjects with diabetes[15] and those who underwent prostatectomy.[16]The avanafil used in this phase III trial was developed by Sichuan Haisco Pharmaceutical Co., Ltd, and its main ingredients, route of administration, indications, and dosage were completely consistent with the originator avanafil. A previous bioequivalence study demonstrated that generic and avanafil tablets were bioequivalent and exhibited similar safety profiles under fasting and branded fed conditions (unpublished work). However, the safety and effectiveness of generic avanafil for ED therapy in a Chinese population has not been unequivocally verified.
Given this background, we carried out a multi-center, randomized, double-blind, placebo-controlled phase III clinical trial of a bioequivalent avanafil tablet (100 mg and 200 mg) in China to evaluate its safety and efficacy for ED therapy after 12-week continuous therapy. We hypothesized that avanafil (100 mg and 200 mg) would be well tolerated and elicit superior improvements in erectile functions over placebo in ED subjects within 12 weeks of the initiation of therapy.
CONCLUSIONS
In conclusion, subject compliance to avanafil was excellent. Chinese developed avanafil exhibited superior efficacy over placebo with good tolerance and can therefore be used to treat Chinese subjects with ED. The results of this phase III clinical trial indicate that avanafil 100 mg should be recommended as the initial dose and up to 200 mg, with an appropriate prescription, if required.
Introduction: The incidence of erectile dysfunction (ED) increases with age in mainland China and phosphodiesterase 5 inhibitors (PDE5i) are the major drugs used for its treatment.
Aim: To determine the efficacy and safety of Chinese developed avanafil as therapy for ED in China.
Methods: This phase III trial was carried out in 7 medical centers in China. Eligible subjects suffering from ED were allocated randomly into 3 groups (ratio 1:1:1) and orally received a placebo, 100 or 200 mg avanafil for a total of 12 weeks.
Main outcome measures: The primary endpoint was changed in erectile function (EF) domain scores according to the International Index of EF (IIEF) questionnaire from baseline to week 12 of therapy. Secondary endpoint assessments were changes in the response rates of SEP, Q2, and Q3; changes in IIEF other domain scores. Safety evaluation monitored treatment-emergent adverse events (TEAEs), serious TEAEs, laboratory test results, vital signs, and electrocardiographs.
Results: Of 218 randomized ED subjects, 182 (83.5%) completed the study. After 12-week therapy, alterations from baseline of the mean IIEF-EF domain scores in the 100 mg and 200 mg groups were greater than for the placebo (all P < .05) group. The changes in mean SEP Q2 response rates from baseline to week 12 in the placebo, 100 mg, and 200 mg groups were 5.4%, 22.3%, and 22.1%, and SEP Q3 response rates were 22.7%, 42.6%, and 38.1%, respectively. Avanafil treatment (regardless of dose) improved EF vs placebo for most of the other secondary efficacy endpoints studied (all P < .05). No differences were detected in efficacy endpoints between the 100 and 200 mg dosage groups (all P > .05) or in the incidence of TEAEs and drug-related TEAEs among the 3 groups (all P > .05).
Conclusion: Avanafil (100 or 200 mg) was effective and generally well-tolerated in Chinese subjects with ED.
INTRODUCTION
Erectile dysfunction (ED) has been characterized as “a persistent or repeated inability to achieve or maintain an adequate penile erection in order to facilitate a satisfactory sexual performance”.[1] The incidence of ED increases with age in mainland China from 20.86% of subjects <30 years old to 93.72% of those >70 years old.[2] Systemic diseases, trauma, and surgery, as well as medication, are closely associated with ED, but they can also be of psychogenic origin. The most common specific physical causes are atherosclerosis, diabetes, and complications following prostate surgery.[3-5]
Currently, phosphodiesterase 5 inhibitors (PDE5i) are administered orally as the initial treatment for ED.[6] Oral PDE5i can inhibit the degradation of cGMP and the elevated cyclic guanosine monophosphate (cGMP) concentration increases the blood volume of the penis and amplifies the neurological signal of erection, thus effectively treating ED.[7] Other treatments include vacuum erection devices,[8] intracavernosal injection of vasoactive substances,[9] low-intensity extracorporeal shock wave therapy,[10] and penile prosthesis surgery.[11]
At present, 3 PDE5i have been approved for sale in China, namely sildenafil, tadalafil, and vardenafil. Avanafil (Stendra) was initially approved by the FDA in the US and was shown to be effective and safe for ED therapy.[12,13] Avanafil is rapidly absorbed after oral administration and the maximum plasma concentration (Cmax) is achieved at a median time to reach Cmax (Tmax) of 30−45 minutes with a relatively short plasma half-life time (3−5 hours).[14] In addition, avanafil has also been shown to be effective in ED subjects with diabetes[15] and those who underwent prostatectomy.[16]The avanafil used in this phase III trial was developed by Sichuan Haisco Pharmaceutical Co., Ltd, and its main ingredients, route of administration, indications, and dosage were completely consistent with the originator avanafil. A previous bioequivalence study demonstrated that generic and avanafil tablets were bioequivalent and exhibited similar safety profiles under fasting and branded fed conditions (unpublished work). However, the safety and effectiveness of generic avanafil for ED therapy in a Chinese population has not been unequivocally verified.
Given this background, we carried out a multi-center, randomized, double-blind, placebo-controlled phase III clinical trial of a bioequivalent avanafil tablet (100 mg and 200 mg) in China to evaluate its safety and efficacy for ED therapy after 12-week continuous therapy. We hypothesized that avanafil (100 mg and 200 mg) would be well tolerated and elicit superior improvements in erectile functions over placebo in ED subjects within 12 weeks of the initiation of therapy.
CONCLUSIONS
In conclusion, subject compliance to avanafil was excellent. Chinese developed avanafil exhibited superior efficacy over placebo with good tolerance and can therefore be used to treat Chinese subjects with ED. The results of this phase III clinical trial indicate that avanafil 100 mg should be recommended as the initial dose and up to 200 mg, with an appropriate prescription, if required.
