population Completed double-blind 458 (67.7) 445 (65.0) study n (%)

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1 Study No: ARIA3002 Year 4 Title: A Randomized, Double-Blind, Placebo-Controlled, Two Year Parallel Group Study of the Efficacy and Safety of GI mg in the Treatment and Prevention of Progression of Benign Prostatic Hyperplasia, Followed by a Two-Year Open-Label Treatment Phase (Report on Open-Label Treatment Phase). Rationale: ARIA3002 is one of three Phase III open-label extension studies, of a similar type and duration, assessing the ongoing safety and tolerability of oral dutasteride (Dut) 0.5mg in males 50 years of age, with benign prostatic hyperplasia (BPH), who completed 24 months of treatment with double-blind, randomized drug (placebo [Pbo] or Dut). Phase: III Study Period: 08 September August 2002 Study Design: Two-year, open-label extension to a randomized 2 year study Centres: 66 in the US Indication: BPH Treatment: Upon completion of 24 months of Dut (Dut/Dut group) or Dut (Pbo/Dut group) therapy, subjects were enrolled into a two-year extension study and were continued on openlabel Dut (0.5 mg) once daily, for up to 24 months (a total duration of 48 months.) Objectives: To assess the safety and tolerability of repeat oral once daily doses of Dut 0.5mg. Primary Outcome Variable: As this was an open-label extension of a 24-month study, the primary outcome variable was safety in terms of adverse events and laboratory safety parameters to assess safety and tolerability. Secondary Outcome Variable: For the open-label phase (Year 4), the secondary efficacy outcomes/variables were the American Urological Association Symptom Index (AUA-SI), total prostate volume, and urinary flow measurements (Qmax). Statistical Methods: The sample size for the open-label phase was based upon the number of subjects who completed the double-blind phase and who subsequently elected to enroll in the open-label phase. Summary statistics for the safety, efficacy, and pharmacodynamic parameters were tabulated by the randomized treatment group of the double-blind phase (Dut/Dut for dutasteride in both the double-blind phase and open-label phase; Pbo/Dut for placebo in the double-blind phase and dutasteride in the open-label phase). The primary population of subjects summarized was the Open-Label Intent-to-Treat population which consisted of all subjects enrolled in the open-label phase (after completing the 24 month double-blind phase) and who received at least one dose of study treatment during the openlabel phase. Study Population: Male subjects 50 years of age, with a diagnosis of BPH, an AUA-SI score of 12, a prostate volume of 30cc as determined by transrectal ultrasound, a urinary flow rate of 15mL/sec with a minimum voided volume of 125mL and to have completed 24 months of double-blind treatment. Subjects were excluded if they had a post void residual volume >250mL or a prostate specific antigen (PSA) level of <1.5ng/mL or >10ng/mL. Number of Subjects: Dut/Dut Pbo/Dut Planned N Randomised N for doubleblind study: Double-blind ITT population Completed double-blind 458 (67.7) 445 (65.0) study n (%) 1

2 Withdrawn double-blind study 219 (32.3) 240 (35.0) n (%) Started open-label study N: Open-label ITT population Completed 48 months of 279 (73.4) 266 (68.9) open-label study n (%) Withdrawn from open-label 101 (26.6) 120 (31.1) study n (%) Withdrawn due to Adverse 34 (9%) 44 (11%) Events n (%) Withdrawn due to Lack of 16 (4%) 22 (6%) Efficacy n (%) Withdrawn for other reasons 51 (14%) 54 (13%) n (%) Demographics Dut/Dut Pbo/Dut N (ITT) Females: Males 0:380 0:386 Mean Age in Years (SD) 66.3 (7.52) 66.5 (6.75) Mean Weight in kg (SD) 86.2 (13.6) 86.2 (13.26) White n (%) 348 (91.6) 361 (93.5) Primary Efficacy Results: The primary outcome for the open-label phase (Year 4) was safety. See adverse events reported below. Secondary Efficacy Results: Open-Label ITT population and At Visit AUA-SI Dut/Dut Pbo/Dut Mean (SD) baseline AUA-SI 16.5 (5.97) 17.1 (6.05) Month 24 n=372 n=381 Mean change from baseline Month 36 n=330 n=322 Mean change from baseline Month 48 n=278 n=264 Mean change from baseline Prostate Volume (cc) Dut/Dut Pbo/Dut Mean (SD) baseline prostate 58.6 (23.94) 54.3 (20.24) volume Month 24 n=377 n=380 Mean percent change from baseline Month 48 n=276 n=260 Mean percent change from baseline Qmax (ml/sec) Dut/Dut Pbo/Dut Mean (SD) baseline Qmax 10.1 (3.27) 10.5 (3.32) Month 24 n=354 n=359 Mean change from baseline Month 36 n=319 n=296 Mean change from baseline Month 48 n=264 n=239 2

3 Mean change from baseline Safety Results: Adverse events were coded and grouped by body system. AE and SAE incidences reported are for the 2-year open-label period. Most Frequent Adverse Dut/Dut Pbo/Dut Events On Therapy N (Open-Label ITT) Subjects with AEs during 295 (78) 307 (80) open-label phase, n (%) Ear nose & throat 37 (10) 30 (8) Hypertension 31 (8) 22 (6) Viral ear nose & throat 30 (8) 22 (6) Disorders of lipid 28 (7) 24 (6) metabolism Musculoskeletal pain 28 (7) 22 (6) Gynecomastia 16 (4) 12 (3) Gastrointestinal 15 (4) 7 (2) Viral respiratory 14 (4) 29 (8) Edema and swelling 14 (4) 7 (2) Urinary 11 (3) 14 (4) Regurgitation & reflux 9 (2) 14 (4) Impotence 8 (2) 20 (5) Coronary artery disorders 18 (5) 7 (2) Serious Adverse Events Dut/Dut Pbo/dut On Therapy during openlabel study period (months 24-48) Subjects with SAEs during 53 (14) [1] 54 (14) [1] open-label study period n (%) [considered by the investigator to be related, possibly related or probably related to study medication] Coronary artery 12 (3) [0] 4 (1) [0] disorders Myocardial infarction 6 (2) [0] 7 (2) [0] Cerebrovascular 3 (<1) [0] 3 (<1) [0] accidents Tachyarrhythmias 3 (<1) [0] 3 (<1) [0] Aneurysms 2 (<1) [0] 3 (<1) [0] Angina pectoris 3 (<1) [0] 1 (<1) [0] Embolisms 0 2 (<1) [0] 3

4 Arterial stenosis & arteriospasm Biventricular heart failure Thrombosis Vascular disorders Symptoms of peripheral ischemia Peripheral ischemia Disturbances of intracranial blood flow Intracranial hemorrhage Myocardial ischemia Heart block 2 (<1) [0] 2 (<1) [0] gastrointestinal neoplasia Diverticulosis 1 (<1) [0] 2 (<1) [0] Viral gastrointestinal Gastroenteritis Salivary disorders Nausea & vomiting Regurgitation & reflux Gastrointestinal hemorrhage Decreased gastrointestinal mobility & ileus Gastrointestinal obstructions Volvulus Gastrointestinal herniae Gastrointestinal polyps lower 3 (<1) [0] 2 (<1) [0] respiratory neoplasia Pneumonia 2 (<1) [0] 2 (<1) [0] Chronic obstructive 0 2 (<1) [0] airways disease Pneumonitis Breathing disorders Lower respiratory failure Pulmonary edema Pleura disorders 1 (<1) [0] 2 (<1) [0] neoplasia Infections 4

5 Death Non-specific conditions Chest symptoms Cholecystitis Pancreatitis Cholelithiasis 2 (<1 ) [0] 0 Primary hepatobiliary & 0 2 (<1) [0] pancreatic malignancy Hepatobiliary symptoms 1 (<1) [1] 0 Abnormal liver function 1 (<1) [1] 0 tests Hepatobiliary & pancreatic cysts lumps & masses Degenerative arthritis Bone & cartilage disorders Arthritis Osteitis osteomyelitis osteochondritis & chondritis Arthralgia & articular rheumatism Renal failure 2 (<1) [0] 1 (<1) [0] Urinary Renal obstructions Urinary tract obstructions Urinary retention Urinary calculi urinary neoplasia Postoperative complications Infections due to medical device or graft Injuries Fractures Fluid disturbances 0 3 (<1) [0] Acidosis Skin 1 (<1) [0] 2 (<1) [0] Bacterial skin blood and lymphatic neoplasia Anemia Quantitative platelet defects 5

6 Reproductive 0 1 (<1) [1] breast neoplasia male reproductive neoplasia Neurological neoplasia of uncertain behavior Benign neurological neoplasia Depressive disorders Subjects with Fatal SAEs 4 (1.1) [0] 7 (1.8) [0] during open-label study period: n (%) [considered by the investigator to be related, possibly related or probably related to study medication] Pulmonary Embolism 0 1 (0.3) [0] Colon Cancer 0 1 (0.3) [0] Sepsis 0 1 (0.3) [0] Metastatic Lung Cancer 1 (0.3) [0] 1 (0.3) [0] Myocardial Infarction 0 1 (0.3) [0] Lung Cancer 0 1 (0.3) [0] Massive Internal Injuries 0 1 (0.3) [0] Kidney Failure 0 1 (0.3) [0] Metabolic Acidosis 1 (0.3) [0] 0 Multisystem Organ 1 (0.3) [0] 0 Failure Metastatic 1 (0.3) [0] 0 Adenocarcinoma Respiratory Failure 1 (0.3) [0] 0 Date Updated: 22-Dec-2004 Publications: Debruyne F, Barkin J, Roehrborn CG. Long-term dutasteride therapy results in continued improvements in symptoms and peak urinary flow in men with symptomatic benign prostatic hyperplasia. EAU 2004 Emberton M. Earlier initiation of treatment with the dual 5alpha reductase inhibitor dutasteride reduces the risk of acute urinary retention and surgical intervention in men with benign prostatic hyperplasia. EAU 2004 Fenter T, Tully A, Debruyne F. Long-term therapy with the dual 5alpha reductase inhibitor dutasteride is well tolerated in men with symptomatic benign prostatic hyperplasia. AUA 2004 Freedman S, Brosman S, Emberton M, et al. Earlier initiation of treatment with the dual 5alpha reductase inhibitor dutasteride reduces the risk of acute urinary retention and surgical intervention in men with benign prostatic hyperplasia. AUA

7 Gittelman M, Barkin J, Zinner N. Sustained prostate volume reduction with dutasteride over 4 years is independent of baseline prostate volume. AUA 2004 Roehrborn C. Dutasteride provides sustained and continued improvement in BPH-related symptoms over 4 years. AUA 2003 Roehrborn CG, Marks L, Fenter T, et al. Long-term dutasteride therapy results in continued improvements in symptoms and peak urinary flow in men with symptomatic benign prostatic hyperplasia. AUA 2004 Roehrborn CG, Dineen M, Bock D, et al. Change in symptom severity status in 4-year dutasteride studies in men with symptomatic BPH. AUA 2004 Tammela T, Barkin J, Roehrborn CG. Long-term dutasteride therapy results in sustained reductions in total prostate volume in men with symptomatic benign prostatic hyperplasia. EAU 2004 Debruyne F, Barkin J, Roehrborn CG. Long-term dutasteride therapy results in continued improvements in symptoms and peak urinary flow in men with symptomatic benign prostatic hyperplasia. EAU 2004 Long-term sustained improvement in symptoms of benign prostatic hyperplasia with the dual 5alpha-reductase inhibitor dutasteride: results of 4-year studies. Roehrborn, C. G., Lukkarinen, O., Mark, S., Siami, P., Ramsdell, J., and Zinner, N. BJU Int 2005; 96 (4): Efficacy and safety of long-term treatment with the dual 5 alpha-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Debruyne, F., Barkin, J., van Erps, P., Reis, M., Tammela, T. L., and Roehrborn, C. Eur Urol 2004; (4. 4):488-94; discussion 495, ; discussion 495. Abstract: efficacy and safety of long-term treatment with the dual 5-alpha-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Debruyne, F., Barkin, J., Van Erps, P., Reis, M., Tammela, T. L., Roehrborn, C., and ARIA3001, 3002 and ARIB3003 Study Investigators 27th Congress of the Societe Internationale durologie 10/3/2004 Honolulu, HI; USA Abstract: effect of dutasteride on tue incidence of prostate cancer (pca) in men with benign prostatic hyperplasia. GeraldAndriole, Claus Roehrborn Claude Schulman Kevin Slawin Matt Somerville Roger Rittmaster. 99th Annual Meeting of the American Urological Association 5/8/2004 Abstract: long-term dutasteride therapy results in continued improvements in symptoms and peak urinary flow in men with symptomatic benign prostatic hyperplasia. Debruyne, F. 2 1, Barkin, J. 3 1, and Roehrbom, C th Congress of the European Association of Urology 3/24/2004 Vienna; Austria 7