Dual PDE-5 inhibitor, 5-ARI therapy improves LUTS

Co-administration of a phosphodiesterase type-5 inhibitor and a 5-alpha-reductase inhibitor significantly improved scores on the International Prostate Symptom Score (IPSS), compared to placebo plus the 5-ARI in men with lower urinary tract symptoms of BPH and enlarged prostates, researchers reported at the European Association of Urology annual congress in Milan, Italy.

On a pre-specified secondary measure, the combination of tadalafil (Cialis) and finasteride (Proscar) also improved erectile function scores versus placebo/finasteride in those men who had both LUTS/BPH and erectile dysfunction at baseline.

"Symptomatic improvement with 5-ARI therapy (finasteride) is observed after 6 to 12 months of treatment; therefore, the study aimed to understand if men with prostatic enlargement experience earlier improvement of BPH symptoms when tadalafil is co-administered with a 5-ARI therapy," said Claus Roehrborn, MD, of the University of Texas Southwestern Medical Center, Dallas, who presented the study results. "These results can help prescribers make better informed decisions when treating their patients."

The randomized, double-blind, placebo-controlled, 26-week trial assessed the efficacy and safety of tadalafil, 5 mg for once daily use, or placebo co-administered with finasteride in 696 men aged 45 years and older with an IPSS of at least 13, a urine flow rate (Qmax) of 4 to 15 mL/sec, and a prostate volume at least 30 mL.

The primary measure was the IPSS, and pre-specified secondary measures included the International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and the Treatment Satisfaction Scale-Benign Prostatic Hyperplasia (TSS-BPH).

Tadalafil/finasteride met the primary endpoint, significantly improving IPSS total scores through 12 weeks versus placebo/finasteride (-5.2 vs. -3.8, p=.001). Tadalafil/finasteride also significantly improved IPSS total scores versus placebo/finasteride at 4 weeks (-3.9 vs. -2.3, p<.001) and 26 weeks (-5.5 vs. -4.5, p=.022).

On the key secondary measure, tadalafil/finasteride improved IIEF-EF scores in sexually active men with ED versus placebo/finasteride at week 4 (2.7 vs. -1.4, p<.001), week 12 (4.2 vs. 0.5, p<.001), and week 26 (3.9 vs. -0.3, p<.001).

The TSS-BPH improved with tadalafil/finasteride versus placebo/finasteride at 26 weeks (2.0 vs. 2.1, p=.031), driven by satisfaction with efficacy (p=.025), with no significant difference for dosing or side effects.

The most common treatment-emergent adverse events were headache (tadalafil/finasteride [3%]; placebo/finasteride [3 %]), indigestion (tadalafil/finasteride [2%]; placebo/finaseteride [.5 %]), and back pain (tadalafil/finasteride [.3%]; placebo/finaseteride 0 [0 %]).

Dr. Roehrborn has been a consultant to Eli Lilly in the area of tadalafil for the BPH and male LUTS indication.