ONCE-DAILY TADALAFIL IMPROVES ERECTILE FUNCTION IN MEN WITH BENIGN PROSTATIC HYPERPLASIA AND AN...
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Vol. 181, No. 4, Supplement, Tuesday, April 28, 2009 THE JOURNAL OF UROLOGY ® 487 RESULTS: Mean age and time from surgery was 58.2 years and 13.1 months respectively, and the average SHIM score was 7. Right and left oximetry measurements were averaged. All techniques significantly (p<0.001) increased corporal and glanular oximetry relative to baseline. No change was observed in thigh oximetry.. Upon comparison with separate, patients cohorts, the VED improved corporal oxygenation comparably to IUA 125 but less than IUA 250 and ICI. CONCLUSIONS: This is the first study demonstrating that a single, brief application of the VED without a constriction ring results in significant improvement in both corporal and glanular oxygen saturation. While IUA 250ug and ICI appear to have improved corporal oximetry to a greater degree in separate, unmatched cohorts, the VED has significant benefits for patients both with regard to cost and invasiveness. This study supports incorporation of the VED in post-prostatectomy penile rehabilitation protocols. Source of Funding: Plethora, 1364 SHORT AND LONG-TERM SAFETY OF SIX ESCALATING DOSES OF HMAXI-K AS POTENTIAL THERAPY FOR MODERATE TO SEVERE ERECTILE DYSFUNCTION OF DIVERSE ETIOLOGY Arnold Melman*, Kelvin P Davies, Bronx, NY; Natan C Bar-Chama, Andrew R McCullough, New York, NY; George J Christ, Winston Salem, NC INTRODUCTION AND OBJECTIVES: This report describes the new results of a phase 1 safety, 7-cohort dose escalating gene transfer trial that employs hMaxi-K (naked DNA vector with the maxi-K gene) as potential therapy for erectile dysfunction. The primary objective was to evaluate all safety parameters occurring subsequent to administration of a single intracavernous injection of hMaxi-K at seven dose levels (500, 1000, 5000, 7500, 8000, 12000, and 16000 μg) in males with erectile dysfunction (ED) longer than six months that is attributable to an underlying, stable medical condition. The target population was men over 18 years of age with moderate to severe erectile dysfunction attributable to an underlying, stable medical condition but who are otherwise in good health. METHODS: In Stage 1, the safety of a single intracavernous injection of hMaxi-K was conducted using dose levels ranging from 500 μg to 7500 μg in nine men. Since these initial doses were well tolerated up through 18 months of follow-up and there was some improvement seen on the IIEF in 2 participants, three higher dose levels were considered for evaluation in Stage 2 in three groups of three men. RESULTS: There have been no serious adverse events related to transfer in either cohort to date. One participant noted transient tingling of the glans penis post- transfer. No evidence of changes in blood chemistries, hormones, EKG’s. No evidence of plasmid being present in the semen of any participant has been found in either cohort. CONCLUSIONS: Safety of the transfer of hMaxi-K gene transfer as a long-acting intracavernous injection for potential therapy for erectile dysfunction has shown no transfer related serious adverse events in 7 sequential escalating doses to men with ED. The observed short and long- term safety of hMaxi-k plasmid based therapy should allow future trials to be initiated with great confidence by the testing sites and the participants so that the trial can be accomplished in an expeditious manner. Source of Funding: Ion Channel Innovations,LLC 1365 ONCE-DAILY TADALAFIL IMPROVES ERECTILE FUNCTION IN MEN WITH BENIGN PROSTATIC HYPERPLASIA AND AN ERECTILE DYSFUNCTION HISTORY INDEPENDENT OF PROSTATE SIZE AND PRIOR -BLOCKER USE Hartmut Porst*, Hamburg, Germany; Kevin T McVary, Chicago, IL; Francesco Montorsi, Milan, Italy; Peter Sutherland, Adelaide, Australia; Albert Elion-Mboussa, Anne M Wolka, Lars Viktrup, Indianapolis, IN INTRODUCTION AND OBJECTIVES: Once-daily tadalafil is currently approved only for the treatment of erectile dysfunction (ED) but is being studied in men with signs and symptoms of benign prostatic hyperplasia (BPH). We report the effects of once-daily tadalafil on erectile function (International Index of Erectile Function-Erectile Function [IIEF- EF] domain score) in men with an ED history and moderate-to-severe lower urinary tract symptoms (LUTS) secondary to BPH. METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel study. Men were not required to have an ED history, and there was no sexual activity threshold for men to participate. Efficacy data, analyzed using analysis of covariance models, are presented as least-squares means ± standard errors. 1 patient randomized at 2 different study sites was excluded from all efficacy analyses. RESULTS: 1056 men (62±8 yr [mean ± standard deviation], International Prostate Symptom Score [IPSS] 13) were randomized and received placebo or tadalafil 2.5, 5, 10, or 20mg once daily for 12 wks. 581 men with LUTS and an ED history reported being sexually active with a female partner and expecting to remain so during the study (ED population: placebo, N=115; 2.5mg, N=113; 5mg, N=117; 10mg, N=120; 20mg, N=116). 68% of men in the ED population had moderate LUTS (IPSS<20) vs 32% with severe LUTS (IPSS 20) at baseline. Improvements in IIEF-EF from baseline to 12 wks for tadalafil were 5.4±1.0 (2.5mg), 6.8±1.0 (5mg), 7.9±1.0 (10mg) and 8.2±1.0 (20mg) vs 2.0±1.0 for placebo (all p<0.001). Changes in IIEF-EF after 12 wks for subgroups are shown in the Table. There were no significant differences between subgroup or subgroup-by-treatment interaction terms. IIEF- EF improvements were significantly greater for all tadalafil groups vs placebo, except 2.5mg tadalafil-treated men with prostate-specific antigen (PSA) 1.5 ng/mL. CONCLUSIONS: Once-daily tadalafil improves erectile function in men with signs and symptoms of BPH and an ED history, overall and independent of prostate size and prior -blocker use. Placebo Tadalafil Tadalafil Tadalafil Tadalafil p-value p-value 2.5mg 5mg 10mg 20mg Subgroup Interaction PSA, ng/ mL <1.5 (n=304) 0.2±0.9 4.2±0.9* 5.6±0.9^ 6.2±0.9^ 6.7±0.9^ 0.184 0.958 1.5 (n=257) 1.8±1.0 4.5±1.0 6.0±1.0* 7.0±1.0^ 7.8±1.0^ Prior -blocker use Yes (n=167) 1.5±1.1 6.0±1.4* 5.6±1.2* 6.1±1.2* 6.9±1.2* 0.768 0.581 No (n=412) 0.8±0.8 3.8±0.8* 6.0±0.8^ 7.2±0.8^ 7.4±0.8^ *p<0.05 vs placebo, ^p<0.001 vs placebo. Patients wtih missing PSA at baseline were excluded from the PSA subgroup analysis. Source of Funding: Lilly ICOS, LLC
Transcript of ONCE-DAILY TADALAFIL IMPROVES ERECTILE FUNCTION IN MEN WITH BENIGN PROSTATIC HYPERPLASIA AND AN...
Vol. 181, No. 4, Supplement, Tuesday, April 28, 2009 THE JOURNAL OF UROLOGY® 487
RESULTS: Mean age and time from surgery was 58.2 years and 13.1 months respectively, and the average SHIM score was 7. Right and left oximetry measurements were averaged. All techniques significantly (p<0.001) increased corporal and glanular oximetry relative to baseline. No change was observed in thigh oximetry.. Upon comparison with separate, patients cohorts, the VED improved corporal oxygenation comparably to IUA 125 but less than IUA 250 and ICI.
CONCLUSIONS: This is the first study demonstrating that a single, brief application of the VED without a constriction ring results in significant improvement in both corporal and glanular oxygen saturation. While IUA 250ug and ICI appear to have improved corporal oximetry to a greater degree in separate, unmatched cohorts, the VED has significant benefits for patients both with regard to cost and invasiveness. This study supports incorporation of the VED in post-prostatectomy penile rehabilitation protocols.
Source of Funding: Plethora,
1364SHORT AND LONG-TERM SAFETY OF SIX ESCALATING DOSES OF HMAXI-K AS POTENTIAL THERAPY FOR MODERATE TO SEVERE ERECTILE DYSFUNCTION OF DIVERSE ETIOLOGY
Arnold Melman*, Kelvin P Davies, Bronx, NY; Natan C Bar-Chama, Andrew R McCullough, New York, NY; George J Christ, Winston Salem, NC
INTRODUCTION AND OBJECTIVES: This report describes the new results of a phase 1 safety, 7-cohort dose escalating gene transfer trial that employs hMaxi-K (naked DNA vector with the maxi-K gene) as potential therapy for erectile dysfunction. The primary objective was to evaluate all safety parameters occurring subsequent to administration of a single intracavernous injection of hMaxi-K at seven dose levels (500, 1000, 5000, 7500, 8000, 12000, and 16000 μg) in males with erectile dysfunction (ED) longer than six months that is attributable to an underlying, stable medical condition. The target population was men over 18 years of age with moderate to severe erectile dysfunction attributable to an underlying, stable medical condition but who are otherwise in good health.
METHODS: In Stage 1, the safety of a single intracavernous injection of hMaxi-K was conducted using dose levels ranging from 500 μg to 7500 μg in nine men. Since these initial doses were well tolerated up through 18 months of follow-up and there was some improvement seen on the IIEF in 2 participants, three higher dose levels were considered for evaluation in Stage 2 in three groups of three men.
RESULTS: There have been no serious adverse events related to transfer in either cohort to date. One participant noted transient tingling of the glans penis post- transfer. No evidence of changes in blood chemistries, hormones, EKG’s. No evidence of plasmid being present in the semen of any participant has been found in either cohort.
CONCLUSIONS: Safety of the transfer of hMaxi-K gene transfer as a long-acting intracavernous injection for potential therapy for erectile dysfunction has shown no transfer related serious adverse events in 7 sequential escalating doses to men with ED. The observed short and long-term safety of hMaxi-k plasmid based therapy should allow future trials to be initiated with great confidence by the testing sites and the participants so that the trial can be accomplished in an expeditious manner.
Source of Funding: Ion Channel Innovations,LLC
1365ONCE-DAILY TADALAFIL IMPROVES ERECTILE FUNCTION IN MEN WITH BENIGN PROSTATIC HYPERPLASIA AND AN ERECTILE DYSFUNCTION HISTORY INDEPENDENT OF PROSTATE SIZE AND PRIOR -BLOCKER USE
Hartmut Porst*, Hamburg, Germany; Kevin T McVary, Chicago, IL; Francesco Montorsi, Milan, Italy; Peter Sutherland, Adelaide, Australia; Albert Elion-Mboussa, Anne M Wolka, Lars Viktrup, Indianapolis, IN
INTRODUCTION AND OBJECTIVES: Once-daily tadalafil is currently approved only for the treatment of erectile dysfunction (ED) but is being studied in men with signs and symptoms of benign prostatic hyperplasia (BPH). We report the effects of once-daily tadalafil on erectile function (International Index of Erectile Function-Erectile Function [IIEF-EF] domain score) in men with an ED history and moderate-to-severe lower urinary tract symptoms (LUTS) secondary to BPH.
METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel study. Men were not required to have an ED history, and there was no sexual activity threshold for men to participate. Efficacy data, analyzed using analysis of covariance models, are presented as least-squares means ± standard errors. 1 patient randomized at 2 different study sites was excluded from all efficacy analyses.
RESULTS: 1056 men (62±8 yr [mean ± standard deviation], International Prostate Symptom Score [IPSS] 13) were randomized and received placebo or tadalafil 2.5, 5, 10, or 20mg once daily for 12 wks. 581 men with LUTS and an ED history reported being sexually active with a female partner and expecting to remain so during the study (ED population: placebo, N=115; 2.5mg, N=113; 5mg, N=117; 10mg, N=120; 20mg, N=116). 68% of men in the ED population had moderate LUTS (IPSS<20) vs 32% with severe LUTS (IPSS 20) at baseline. Improvements in IIEF-EF from baseline to 12 wks for tadalafil were 5.4±1.0 (2.5mg), 6.8±1.0 (5mg), 7.9±1.0 (10mg) and 8.2±1.0 (20mg) vs 2.0±1.0 for placebo (all p<0.001). Changes in IIEF-EF after 12 wks for subgroups are shown in the Table. There were no significant differences between subgroup or subgroup-by-treatment interaction terms. IIEF-EF improvements were significantly greater for all tadalafil groups vs placebo, except 2.5mg tadalafil-treated men with prostate-specific antigen (PSA) 1.5 ng/mL.
CONCLUSIONS: Once-daily tadalafil improves erectile function in men with signs and symptoms of BPH and an ED history, overall and independent of prostate size and prior -blocker use.
Placebo Tadalafil Tadalafil Tadalafil Tadalafil p-value p-value
2.5mg 5mg 10mg 20mg Subgroup Interaction
PSA, ng/mL
<1.5 (n=304) 0.2±0.9 4.2±0.9* 5.6±0.9^ 6.2±0.9^ 6.7±0.9^ 0.184 0.958
1.5 (n=257) 1.8±1.0 4.5±1.0 6.0±1.0* 7.0±1.0^ 7.8±1.0^
Prior -blocker
use
Yes (n=167) 1.5±1.1 6.0±1.4* 5.6±1.2* 6.1±1.2* 6.9±1.2* 0.768 0.581
No (n=412) 0.8±0.8 3.8±0.8* 6.0±0.8^ 7.2±0.8^ 7.4±0.8^
*p<0.05 vs placebo, ^p<0.001 vs placebo. Patients wtih missing PSA at baseline were excluded from the PSA subgroup analysis.
Source of Funding: Lilly ICOS, LLC
