Eli Lilly and Company (NYSE: LLY) announced today that a pivotal Phase III study of Cialis® (tadalafil) tablets 5 mg for once daily use met its co-primary endpoints, significantly improving measures of both erectile dysfunction (ED) and signs and symptoms of benign prostatic hyperplasia (BPH) in men with both conditions. The study is available online in The Journal of Sexual Medicine. It is one of three efficacy and safety studies included in the supplemental new drug application Lilly submitted to the U.S. Food and Drug Administration (FDA) last year seeking approval for Cialis in the treatment of the signs and symptoms of BPH and the treatment of both ED and the signs and symptoms of BPH (ED+BPH).
The FDA approved Cialis on Thursday for both new indications.
It is important to note that Cialis is not to be taken with medicines called "nitrates" (often prescribed for chest pain); or with recreational drugs called "poppers" like amyl or butyl nitrite, as the combination may cause an unsafe drop in blood pressure; or if allergic to Cialis or Adcirca® (tadalafil), or any of its ingredients. Anyone who experiences any symptoms of an allergic reaction, such as rash or hives, should call a healthcare provider or get help right away.
"We are pleased with the outcomes of this study," said Anthony Beardsworth, M.D., senior medical director for Eli Lilly and Company. "Lilly is committed to research that can help us offer new treatment options and advance our understanding of ED and BPH, conditions that affect millions of men worldwide."
About the Study
The study assessed the effects of Cialis 2.5 mg or 5 mg for once daily use on ED and the symptoms of BPH in men with both conditions. It is the first Lilly-sponsored study that evaluated the effect of Cialis exclusively in male patients with both ED and BPH symptoms.
The Phase III randomized, double-blind, placebo-controlled, parallel-design clinical study, conducted in 54 urology centers in nine countries, assessed the safety and efficacy of Cialis 2.5 or 5 mg for once daily use in 606 sexually active men aged 45 years and older who had experienced ED for at least 3 months and BPH symptoms for more than 6 months. The men were randomly assigned to receive placebo, Cialis 2.5 mg, or Cialis 5 mg in a 1:1:1 ratio for a period of 12 weeks.
The co-primary measures were the changes from baseline to week 12 of the International Index of Erectile Function-Erectile Function Domain (IIEF EF), a questionnaire evaluating sexual function where higher scores indicate better erectile function, and the International Prostate Symptom Score (IPSS), a questionnaire evaluating lower urinary tract symptoms occurring during the preceding month where lower scores indicate less severe symptoms. Key secondary measures were the change during treatment in the percentage of "yes" responses to question three of the Sexual Encounter Profile (SEP Q3) and BPH Impact Index (BII). The SEP Q3 asks "Did your erection last long enough for you to have successful intercourse?" The BII is a questionnaire evaluating the impact of urinary problems on overall health and activity, with lower scores indicating less impact.
Cialis 5 mg for once daily use significantly improved the mean differences from baseline on IIEF-EF Domain scores and IPSS scores through 12 weeks versus placebo (4.7 and -2.3, respectively, both P<0.001). For the 2.5 mg once daily dose, significant improvements were seen versus placebo on IIEF EF Domain scores at 12 weeks (3.4, P<0.001), but the difference from placebo in IPSS scores was not significant after 12 weeks (-0.8, P=0.18).
On the key secondary measures, the mean differences from baseline with Cialis 5 mg compared to placebo after 12 weeks were 19.7% (P<0.001) on the SEP Q3 and -0.9 (P<0.001) on the BII. Cialis 2.5 mg for once daily use significantly improved the SEP Q3 (mean difference from baseline compared to placebo 12.5 %, P<0.001), but the reduction in the BII was not significant (-0.4 versus placebo, P=0.16).
The overall incidences of treatment-emergent adverse events (TEAEs) were: 19.5 % in patients treated with placebo, 25.3% in patients treated with Cialis 2.5 mg, and 27.4% in patients treated with Cialis 5 mg. The most common TEAEs in the Cialis 5 mg group were headache (5.8% versus 3% in placebo group), back pain (2.9% versus 1.5% in placebo group), and nasopharyngitis (2.4% versus 2.0% in placebo group). There were no reports of ejaculatory dysfunction or urinary retention in any treatment group.
"It is encouraging that Cialis at 5 mg showed the potential to treat both ED and BPH symptoms," said lead author Blair Egerdie, M.D., Urologic Medical Research in Kitchener, Canada. "Given that the prevalence of coexisting ED and BPH is high, especially in older men, I believe that a single medical therapy approved to treat both conditions is a valuable therapeutic option."
About ED and BPH
ED is a condition where the penis does not fill with enough blood to harden and expand when a man is sexually excited, or when he cannot keep an erection. Approximately 50 percent of men between 40-70 years old have ED.(1)
BPH is a condition where the prostate enlarges, which can cause urinary symptoms.
ED and BPH are conditions that may occur in the same patient. Several studies have shown that many men with ED also experience the symptoms of BPH.(2-4)
About Cialis
Men with ED have two different dosing options with Cialis in the United States - Cialis for once daily use (2.5 mg and 5 mg) and Cialis for use as needed (5 mg, 10 mg and 20 mg).
Cialis for once daily use is approved to treat ED, the signs and symptoms of BPH, and ED and the signs and symptoms of BPH in men who have both conditions (ED+BPH). Only the 5 mg dose is approved to treat BPH and ED+BPH.
Cialis for once daily use can help men with ED be ready anytime between doses*, so they do not have to plan sexual activity around taking a pill. It can also treat the signs and symptoms of BPH. Cialis for once daily use is the only medication approved to treat both ED and the signs and symptoms of BPH.
Cialis for use as needed is approved to treat erectile dysfunction (ED). Cialis for use as needed should be taken before sexual activity. It may go to work quickly (in as little as 30 minutes in some men) and can work up to 36 hours.* #
The most common side effects with Cialis are headache, indigestion, back pain, muscle aches, flushing and stuffy or runny nose. These side effects usually go away after a few hours. Men who get back pain and muscle aches usually get it 12 to 24 hours after taking Cialis. Back pain and muscle aches usually go away within two days.
* Individual results may vary. Not studied for multiple attempts per dose.
# In clinical trials, Cialis for use as needed was shown to improve, up to 36 hours after dosing, the ability of men with ED to have a single successful intercourse attempt.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs.
Cialis® (tadalafil) is a registered trademark of Eli Lilly and Company.
1. Feldman HA et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994 Jan;151(1):54-61.
2. Rosen R, Altwein J, Boyle P, Roger SK, Lukacs B, Meuleman E, et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol. 2003;44(6):637-649.
3. Brookes ST, Link CL, Donovan JL, and McKinlay JB. Relationship between lower urinary tract symptoms and erectile dysfunction: results from the Boston Area community Health Survey. J Urol 2008;179:250-255.
4. Gacci M, et al. Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia. In press. Eur Urol 2011; doi:10.1016/j.eururo.2011.06.037.