Issued — Tuesday 4 September 2007, London, UK

 

GlaxoSmithKline today announced new results from a large study that demonstrate combination treatment with Avodart ^® (dutasteride) and the alpha blocker, tamsulosin, provides significantly greater urinary symptom improvement for men with enlarged prostate than either Avodart or tamsulosin monotherapy over 24 months. Three analyses from the study — Combination therapy with A vodart and tamsulosin (CombAT) — were presented today at the 29th annual meeting of the Société Internationale d'Urologie in Paris.

In addition, one of the CombAT analyses, which was conducted post-hoc, showed that Avodart provides a pattern of increasing enlarged prostate symptom improvement over 24 months. Tamsulosin — the most commonly prescribed medicine for the condition — showed a plateau in symptom improvement¹ from month three through 24. Common symptoms of enlarged prostate include frequent urge to urinate or difficulty emptying the bladder.

The CombAT study includes 4,800 men (combination therapy, n=1492; Avodart, n=1502; tamsulosin, n=1519) with moderate-to-severe enlarged prostate symptoms. All study participants received placebo for four weeks and then were randomized to receive Avodart and tamsulosin combination therapy, Avodart monotherapy or tamsulosin monotherapy.^1,2

Enlarged prostate, also known as benign prostatic hyperplasia (BPH), is a condition that affects 50 per cent of men over the age of 50 and more than 90 per cent of men over age 80.³ Avodart belongs to a class of medicines known as 5 alpha reductase inhibitors (5 ARIs), which shrink the prostate over time. Tamsulosin is an alpha blocker, a class of medicines that relaxes muscles in the bladder and prostate.⁴

“This trial suggests that physicians should consider combining Avodart and tamsulosin as initial therapy to achieve improved symptom relief for men with enlarged prostate,” said Professor Claus Roehrborn, from the University of Texas, who presented the new data. “This study provides important new data to guide medical therapy for men with symptomatic BPH.”

CombAT two-year results

The findings reported today are intermediate results from a study that is still on going. Researchers will issue a final report at the end of four years regarding the efficacy of Avodart, tamsulosin, and combination therapy in reducing the risk of symptomatic disease progression, and the risk of acute urinary retention (AUR) and prostate surgery in men with moderate-to-severe enlarged prostate symptoms.¹

Poster presentation: “The effects of dutasteride, tamsulosin, and combination therapy on lower urinary tract symptoms and Qmax in men with BPH and prostatic enlargement”
According to this analysis, the two-year primary endpoint was achieved in the CombAT study. Over 24 months, Avodart and tamsulosin combination therapy provided a significantly greater (p<0.001) improvement in symptoms (IPSS) from baseline (6.2 units) than either Avodart (4.9 units) or tamsulosin (4.3 units) treatment alone. In fact, the CombAT study demonstrated the benefit of combination therapy over both monotherapies in the first 12 months of treatment. With combination therapy, patients experienced continuous improvement of symptoms throughout the two years of the study. ²

Poster presentation: “Dutasteride provides greater improvement in symptoms and Qmax than tamsulosin in men with moderate-to-severe symptoms of BPH and prostate enlargement”
This post-hoc analysis of the CombAT two-year data is a comparison of efficacy for Avodart and tamsulosin monotherapies. According to the post-hoc analysis, Avodart monotherapy resulted in a pattern of continuous and increasing symptom improvement over 2 years (IPSS: 4.9 units). By comparison, patients taking tamsulosin showed similar symptom improvement from Month 3 to Month 24 (IPSS at Month 3: 4.5 units; IPSS at Month 24: 4.3 units). Furthermore, Avodart resulted in continuous and sustained Qmax (urine flow rate) improvements to Month 24.

All therapy regimens employed in the study appear to be generally well-tolerated. The profile of events for combination therapy was consistent with those reported for monotherapies. The most common adverse events for combination therapy were erectile dysfunction (7.4%), retrograde ejaculation (4.2%) and altered or decreased libido (3.4%). The most common adverse events for Avodart monotherapy were erectile dysfunction (6.0%), altered or decreased libido (2.8%) and breast enlargement (1.8%), while the most common adverse events for tamsulosin monotherapy were erectile dysfunction (3.8%), altered or decreased libido (1.7%) and dizziness (1.7%).⁵

About CombAT

CombAT is a multicenter, randomized, double-blind and parallel-group study. Men [aged ≥50 years with a prostate volume (PV) ≥30 cc, serum prostate-specific antigen (PSA) level 1.5-10 ng/mL, Qmax >5 mL/sec and ≤15 mL/sec with a minimum voided volume ≥125 mL and International Prostate Symptom Score (IPSS) ≥12] with moderate-to-severe enlarged prostate symptoms received placebo for four weeks and were then randomized to receive Avodart 0.5 mg/day and tamsulosin 0.4 mg/day (n=1492), Avodart 0.5 mg/day (n=1502), or tamsulosin 0.4 mg/day (n=1519).^1,2

About Avodart

Avodart, the first and only dual 5ARI for the treatment of enlarged prostate, inhibits both the type I and type II isoenzymes responsible for the conversion of testosterone into dihydrotestosterone (DHT). DHT is the primary male hormone responsible for the enlargement of the prostate. Avodart provides the power to suppress DHT by 93 per cent at 2 years. Over time, Avodart reduces prostate volume, improves symptoms and arrests the enlarged prostate disease process.

Avodart is indicated for the treatment of symptomatic enlarged prostate in men with an enlarged prostate to improve urinary symptoms, reduce the risk of AUR, and reduce the risk of enlarged prostate-related surgery. While some men have fewer problems and symptoms after three months of treatment with Avodart, a treatment period of at least six months is usually necessary to see if Avodart will improve symptoms.

Only a doctor can tell if symptoms are from an enlarged prostate and not a more serious condition such as prostate cancer. Men should see their doctors for regular exams. Women and children should not take Avodart. Women who are, or could become pregnant should not handle Avodart due to the potential risk of a specific birth defect. Men treated with Avodart should not donate blood until at least six months after their final dose.

Caution should be used in patients with liver disease. Possible side effects include sexual side effects and breast tenderness and/or swelling. These side effects occur infrequently.

About enlarged prostate

Enlarged prostate is a prevalent and progressive condition that affects 50 per cent of men over 50 years of age and over 90 per cent of men older than age 80.³ An enlarged prostate causes changes in urinary habits because of its location around the urethra. Over time, the prostate can continue to grow and urinary symptoms may worsen as the bladder loses the ability to empty itself. Left untreated, in severe cases, an enlarged prostate can lead to serious long-term problems including acute urinary retention (AUR) and the need for surgery, and in rare cases even kidney or bladder damage.⁶

About GlaxoSmithKline

GlaxoSmithKline — one of the world’s leading research-based pharmaceutical and healthcare companies — is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

References:

1. C Roehrborn, P Siami, J Barkin, R Damião, F Montorsi. “Dutasteride provides greater improvement in symptoms and Qmax than tamsulosin in men with moderate-to-severe symptoms of BPH and prostate enlargement: Two-year results from the Combination of Avodart^® and Tamsulosin (CombAT) study.” Société Internationale d'Urologie. 2007. Paris, France

2. C Roehrborn, P Siami, J Barkin, R Damião, F Montorsi. “The effects of dutasteride, tamsulosin, and combination therapy on lower urinary tract symptoms and Qmax in men with BPH and prostatic enlargement: Two-year results from the Combination of Avodart^® and Tamsulosin (CombAT) study.” Société Internationale d'Urologie. 2007. Paris, France.

3. Presti JC Jr. Neoplasms of the prostate gland. In: Tanagho EA, McAninch JW, eds. Smith’s General Urology 15^th ed. New York, NY: Lange Medical Books/McGraw-Hill Professions Division: 2000:399-421.

4. American Urological Association. “Miminally Invasive Management of BPH.” Available at http://www.urologyhealth.org/. Accessed on August 13, 2007.

5. C Roehrborn, P Siami, J Barkin, R Damião, F Montorsi. “Safety and tolerability of dutasteride, tamsulosin and a combination of dutasteride and tamsulosin: Two-year results from the Combination of Avodart^® and Tamsulosin (CombAT) study.” Société Internationale d'Urologie. 2007. Paris, France.

6. American Urological Association Foundation. “Enlarged Prostate.” Available at www.urologyhealth.org/content/moreinfo/enlargedprostate.pdf. Accessed on August 13, 2007.

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