FDA label 3539a899-027b-1863-e063-6394a90acc08

5 WARNINGS AND PRECAUTIONS Mineralocorticoid excess: Closely monitor patients with cardiovascular disease. Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly. ( 5.1 ) Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations. ( 5.2 ) Hepatotoxicity: Can be severe and fatal. Monitor liver function and modify, interrupt, or discontinue abiraterone acetate tablets dosing as recommended. ( 5.3 ) Increased fractures and mortality in combination with radium Ra 223 dichloride: Use of abiraterone acetate tablets plus prednisone/prednisolone in combination with radium Ra 223 dichloride is not recommended. ( 5.4 ) Embryo-Fetal Toxicity: Abiraterone acetate tablets can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception. ( 5.5 , 8.1 , 8.3 ) Hypoglycemia: Severe hypoglycemia has been reported in patients with pre-existing diabetes who are taking medications containing thiazolidinediones (including pioglitazone) or repaglinide. Monitor blood glucose in patients with diabetes and assess if antidiabetic agent dose modifications are required. (5.6) 5.1 Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess Abiraterone acetate tablets may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [ see Clinical Pharmacology (12.1) ]. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with abiraterone acetate tablets. In the combined data from 4 placebo-controlled trials using prednisone 5 mg twice daily in combination with 1000 mg abiraterone acetate daily, grades 3 to 4 hypokalemia were detected in 4% of patients on the abiraterone acetate tablets arm and 2% of patients on the placebo arm. Grades 3 to 4 hypertension were observed in 2% of patients each arm and grades 3 to 4 fluid retention in 1% of patients each arm. In LATITUDE (a randomized placebo-controlled, multicenter clinical trial), which used prednisone 5 mg daily in combination with 1,000 mg abiraterone acetate daily, grades 3-4 hypokalemia were detected in 10% of patients on the abiraterone acetate tablets arm and 1% of patients on the placebo arm, grades 3-4 hypertension were observed in 20% of patients on the abiraterone acetate tablets arm and 10% of patients on the placebo arm. Grades 3-4 fluid retention occurred in 1% of patients each arm [see Adverse Reactions ( 6 )] . Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. In postmarketing experience, QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking abiraterone acetate tablets. The safety of abiraterone acetate tablets in patients with left ventricular ejection fraction <50% or New York Heart Association (NYHA) Class III or IV heart failure (in COU-AA-301) or NYHA Class II to IV heart failure (in COU-AA-302 and LATITUDE) has not been established because these patients were excluded from these randomized clinical trials [ see Clinical Studies (14) ]. 5.2 Adrenocortical Insufficiency Adrenal insufficiency occurred in 0.3% of 2230 patients taking abiraterone acetate tablets and in 0.1% of 1763 patients taking placebo in the combined data of randomized, placebo-controlled clinical studies. Adrenocortical insufficiency was reported in patients receiving abiraterone acetate tablets in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with abiraterone acetate tablets. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations [see Warnings and Precautions (5.1) ]. 5.3 Hepatotoxicity In postmarketing experience, there have been abiraterone acetate tablets-associated severe hepatic toxicity, including fulminant hepatitis, acute liver failure and deaths [see Adverse Reactions ( 6.2 )] . In the combined data of randomized clinical trials, grade 3 to 4 ALT or AST increases (at least 5X ULN) were reported in 6% of 2230 patients who received abiraterone acetate tablets, typically during the first 3 months after starting treatment. Patients whose baseline ALT or AST were elevated were more likely to experience liver test elevation than those beginning with normal values. Treatment discontinuation due to ALT and AST increases or abnormal hepatic function occurred in 1.1% of 2230 patients taking abiraterone acetate tablets. In these clinical trials, no deaths clearly related to abiraterone acetate tablets were reported due to hepatotoxicity events. Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with abiraterone acetate tablets, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced abiraterone acetate tablets dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient's baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the ULN, or the bilirubin rises above three times the ULN, interrupt abiraterone acetate tablets treatment and closely monitor liver function. Re-treatment with abiraterone acetate tablets at a reduced dose level may take place only after return of liver function tests to the patient's baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN [ see Dosage and Administration (2.4) ]. Permanently discontinue abiraterone acetate tablets for patients who develop a concurrent elevation of ALT greater than 3 x ULN and total bilirubin greater than 2 x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation [ see Dosage and Administration (2.4) ]. The safety of abiraterone acetate tablets re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown. 5.4 Increased Fractures and Mortality in Combination with Radium Ra 223 Dichloride Abiraterone acetate tablets plus prednisone/prednisolone is not recommended for use in combination with radium Ra 223 dichloride outside of clinical trials. The clinical efficacy and safety of concurrent initiation of abiraterone acetate tablets plus prednisone/prednisolone and radium Ra 223 dichloride was assessed in a randomized, placebo-controlled multicenter study (ERA-223 trial) in 806 patients with asymptomatic or mildly symptomatic castration-resistant prostate cancer with bone metastases. The study was unblinded early based on an Independent Data Monitoring Committee recommendation. At the primary analysis, increased incidences of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) have been observed in patients who received abiraterone acetate tablets plus prednisone/prednisolone in combination with radium Ra 223 dichloride compared to patients who received placebo in combination with abiraterone acetate tablets plus prednisone/prednisolone. 5.5 Embryo-Fetal Toxicity The safety and efficacy of abiraterone acetate tablets have not been established in females. Based on animal reproductive studies and mechanism of action, abiraterone acetate tablets can cause fetal harm and loss of pregnancy when administered to a pregnant female. In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures approximately ≥ 0.03 times the human exposure (AUC) at the recommended dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with abiraterone acetate tablets and for 3 weeks after the last dose of abiraterone acetate tablets [ see Use in Specific Populations ( 8.1 , 8.3 ) ]. Abiraterone acetate tablets should not be handled by females who are or may become pregnant [ see How Supplied/Storage and Handling (16) ]. 5.6 Hypoglycemia Severe hypoglycemia has been reported when abiraterone acetate tablets was administered to patients with preexisting diabetes receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide [see Drug Interactions ( 7.2 )] . Monitor blood glucose in patients with diabetes during and after discontinuation of treatment with abiraterone acetate tablets. Assess if antidiabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia.

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess [ see Warnings and Precautions (5.1) ]. Adrenocortical Insufficiency [ see Warnings and Precautions (5.2) ]. Hepatotoxicity [ see Warnings and Precautions (5.3) ]. Increased Fractures and Mortality in Combination with Radium Ra 223 Dichloride [ see Warnings and Precautions (5.4) ]. The most common adverse reactions (≥10%) are fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. ( 6.1 ) The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Wockhardt USA LLC. at 1-800-346-6854 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Two randomized placebo-controlled, multicenter clinical trials (COU-AA-301 and COU-AA-302) enrolled patients who had metastatic CRPC in which abiraterone acetate tablets was administered orally at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to patients on the control arm. A third randomized placebo-controlled, multicenter clinical trial (LATITUDE) enrolled patients who had metastatic high-risk CSPC in which abiraterone acetate tablets was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg once daily. Placebos were administered to patients in the control arm. Additionally, two other randomized, placebo-controlled trials were conducted in patients with metastatic CRPC. The safety data pooled from 2230 patients in randomized controlled trials constitute the basis for the data presented in the Warnings and Precautions, Grade 1 to 4 adverse reactions, and Grade 1 to 4 laboratory abnormalities. In all trials, a gonadotropin-releasing hormone (GnRH) analog or prior orchiectomy was required in both arms. In the pooled data, median treatment duration was 11 months (0.1, 43) for abiraterone acetate tablets-treated patients and 7.2 months (0.1, 43) for placebo-treated patients. The most common adverse reactions (≥10%) that occurred more commonly (>2%) in the abiraterone acetate tablets arm were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache. The most common laboratory abnormalities (>20%) that occurred more commonly (≥2%) in the abiraterone acetate tablets arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, and hypokalemia. Grades 3 to 4 adverse events were reported for 53% of patients in the abiraterone acetate tablets arm and 46% of patients in the placebo arm. Treatment discontinuation was reported in 14% of patients in the abiraterone acetate tablets arm and 13% of patients in the placebo arm. The common adverse events (≥1%) resulting in discontinuation of abiraterone acetate tablets and prednisone were hepatotoxicity and cardiac disorders. Deaths associated with treatment-emergent adverse events were reported for 7.5% of patients in the abiraterone acetate tablets arm and 6.6% of patients in the placebo arm. Of the patients in the abiraterone acetate tablets arm, the most common cause of death was disease progression (3.3%). Other reported causes of death in ≥5 patients included pneumonia, cardio-respiratory arrest, death (no additional information), and general physical health deterioration. COU-AA-301: Metastatic CRPC Following Chemotherapy COU-AA-301 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. Patients were not eligible if AST and/or ALT ≥2.5X ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5X ULN. Table 1 shows adverse reactions on the abiraterone acetate tablets arm in COU-AA-301 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with abiraterone acetate tablets with prednisone was 8 months. Table 1: Adverse Reactions due to Abiraterone Acetate Tablets in COU-AA-301 1 Adverse events graded according to CTCAE version 3. 2 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. 3 Includes terms Muscle spasms, Musculoskeletal pain, Myalgia, Musculoskeletal discomfort, and Musculoskeletal stiffness. 4 Includes terms Edema, Edema peripheral, Pitting edema, and Generalized edema. 5 Includes all fractures with the exception of pathological fracture. 6 Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia. 7 Includes terms Angina pectoris, Chest pain, and Angina unstable. Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the abiraterone acetate tablets arm (1.3% vs. 1.1% respectively). 8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased. Abiraterone Acetate Tablets with Prednisone Placebo with Prednisone (N=791) (N=394) System/Organ Class All Grades 1 Grade 3 to 4 All Grades Grade 3 to 4 Adverse reaction % % % % Musculoskeletal and connective tissue disorders Joint swelling/discomfort 2 30 4.2 23 4.1 Muscle discomfort 3 26 3 23 2.3 General disorders Edema 4 27 1.9 18 0.8 Vascular disorders Hot flush 19 0.3 17 0.3 Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disorders Diarrhea 18 0.6 14 1.3 Dyspepsia 6.1 0 3.3 0 Infections and infestations Urinary tract infection 12 2.1 7.1 0.5 Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinal disorders Cough 11 0 7.6 0 Renal and urinary disorders Urinary frequency 7.2 0.3 5.1 0.3 Nocturia 6.2 0 4.1 0 Injury, poisoning and procedural complications Fractures 5 5.9 1.4 2.3 0 Cardiac disorders Arrhythmia 6 7.2 1.1 4.6 1 Chest pain or chest discomfort 7 3.8 0.5 2.8 0 Cardiac failure 8 2.3 1.9 1 0.3 Table 2 shows laboratory abnormalities of interest from COU-AA-301. Table 2: Laboratory Abnormalities of Interest in COU-AA-301 Abiraterone Acetate Tablets with Prednisone (N=791) Placebo with Prednisone (N=394) Laboratory Abnormality All Grades (%) Grade 3 to 4 (%) All Grades (%) Grade 3 to 4 (%) Hypertriglyceridemia 63 0.4 53 0 High AST 31 2.1 36 1.5 Hypokalemia 28 5.3 20 1 Hypophosphatemia 24 7.2 16 5.8 High ALT 11 1.4 10 0.8 High Total Bilirubin 6.6 0.1 4.6 0 COU-AA-302 : Metastatic CRPC Prior to Chemotherapy COU-AA-302 enrolled 1088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5X ULN and patients were excluded if they had liver metastases. Table 3 shows adverse reactions on the abiraterone acetate tablets arm in COU-AA-302 that occurred in ≥5% of patients with a ≥2% absolute increase in frequency compared to placebo. The median duration of treatment with abiraterone acetate tablets with prednisone was 13.8 months. Table 3: Adverse Reactions in ≥5% of Patients on the Abiraterone Acetate Tablets Arm in COU-AA-302 1 Adverse events graded according to CTCAE version 3. 2 Includes terms Edema peripheral, Pitting edema, and Generalized edema. 3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. Abiraterone Acetate Tablets with Prednisone Placebo with Prednisone (N=542) (N=540) System/Organ Class Adverse reaction All Grades 1 Grade 3 to 4 All Grades Grade 3 to 4 % % % % General disorders Fatigue 39 2.2 34 1.7 Edema 2 25 0.4 21 1.1 Pyrexia 8.7 0.6 5.9 0.2 Musculoskeletal and connective tissue disorders Joint swelling/discomfort 3 30 2 25 2 Groin pain 6.6 0.4 4.1 0.7 Gastrointestinal disorders Constipation 23 0.4 19 0.6 Diarrhea 22 0.9 18 0.9 Dyspepsia 11 0 5 0.2 Vascular disorders Hot flush 22 0.2 18 0 Hypertension 22 3.9 13 3 Respiratory, thoracic and mediastinal disorders Cough 17 0 14 0.2 Dyspnea 12 2.4 9.6 0.9 Psychiatric disorders Insomnia 14 0.2 11 0 Injury, poisoning and procedural complications Contusion 13 0 9.1 0 Falls 5.9 0 3.3 0 Infections and infestations Upper respiratory tract infection 13 0 8 0 Nasopharyngitis 11 0 8.1 0 Renal and urinary disorders Hematuria 10 1.3 5.6 0.6 Skin and subcutaneous tissue disorders Rash 8.1 0 3.7 0 Table 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the abiraterone acetate tablets arm compared to placebo in COU-AA-302. Table 4: Laboratory Abnormalities in >15% of Patients in the Abiraterone Acetate Tablets Arm of COU-AA-302 1 Based on non-fasting blood draws. Abiraterone Acetate Tablets with Prednisone (N=542) Placebo with Prednisone (N=540) Grade 1 to 4 Grade 3 to 4 Grade 1 to 4 Grade 3 to 4 Laboratory Abnormality % % % % Hematology Lymphopenia 38 8.7 32 7.4 Chemistry Hyperglycemia 1 57 6.5 51 5.2 High ALT 42 6.1 29 0.7 High AST 37 3.1 29 1.1 Hypernatremia 33 0.4 25 0.2 Hypokalemia 17 2.8 10 1.7 LATITUDE: Patients with Metastatic High-risk CSPC LATITUDE enrolled 1199 patients with newly-diagnosed metastatic, high-risk CSPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5 x ULN or if they had liver metastases. All the patients received GnRH analogs or had prior bilateral orchiectomy during the trial. The median duration of treatment with abiraterone acetate tablets and prednisone was 24 months. Table 5 shows adverse reactions on the abiraterone acetate tablets arm that occurred in ≥5% of patients with a ≥2% absolute increase in frequency compared to those on the placebos arm. Table 5: Adverse Reactions in ≥5% of Patients on the Abiraterone Acetate Tablets Arm in LATITUDE 1 1 All patients were receiving an GnRH agonist or had undergone orchiectomy. 2 Adverse events graded according to CTCAE version 4.0 3 Reported as an adverse event or reaction 4 Including cough, productive cough, upper airway cough syndrome Abiraterone Acetate Tablets with Prednisone Placebos (N=597) (N=602) System/Organ Class Adverse reaction All Grades 2 Grade 3 to 4 All Grades Grade 3 to 4 % % % % Vascular disorders Hypertension 37 20 13 10 Hot flush 15 0.0 13 0.2 Metabolism and nutrition disorders Hypokalemia 20 10 3.7 1.3 Investigations Alanine aminotransferase increased 3 16 5.5 13 1.3 Aspartate aminotransferase increased 3 15 4.4 11 1.5 Infections and infestations Urinary tract infection 7.0 1.0 3.7 0.8 Upper respiratory tract infection 6.7 0.2 4.7 0.2 Nervous system disorders Headache 7.5 0.3 5.0 0.2 Respiratory, thoracic and mediastinal disorders Cough 4 6.5 0.0 3.2 0 Table 6 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the abiraterone acetate tablets arm compared to placebos. Table 6: Laboratory Abnormalities in >15% of Patients in the Abiraterone Acetate Tablets Arm of LATITUDE Abiraterone Acetate Tablets with Prednisone (N=597) Placebos (N=602) Grade 1 to 4 Grade 3 to 4 Grade 1 to 4 Grade 3 to 4 Laboratory Abnormality % % % % Hematology Lymphopenia 20 4.1 14 1.8 Chemistry Hypokalemia 30 9.6 6.7 1.3 Elevated ALT 46 6.4 45 1.3 Elevated total bilirubin 16 0.2 6.2 0.2 Cardiovascular Adverse Reactions In the combined data of randomized, placebo-controlled clinical studies, cardiac failure occurred more commonly in patients on the abiraterone acetate tablets arm compared to patients on the placebo arm (2.6% versus 0.9%). Grade 3 to 4 cardiac failure occurred in 1.3% of patients taking abiraterone acetate tablets and led to 5 treatment discontinuations and 4 deaths. Grade 3 to 4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and two deaths due to cardiac failure in the placebo group. In the same combined data, the majority of arrhythmias were grade 1 or 2. There was one death associated with arrhythmia and three patients with sudden death in the abiraterone acetate tablets arms and five deaths in the placebo arms. There were 7 (0.3%) deaths due to cardiorespiratory arrest in the abiraterone acetate tablets arms and 2 (0.1%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 3 deaths in the abiraterone acetate tablets arms. 6.2 Postmarketing Experience The following additional adverse reactions have been identified during post approval use of abiraterone acetate tablets with prednisone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Respiratory, Thoracic and Mediastinal Disorders : non-infectious pneumonitis. Musculoskeletal and Connective Tissue Disorders : myopathy, including rhabdomyolysis. Hepatobiliary Disorders : fulminant hepatitis, including acute hepatic failure and death. Cardiac Disorders : QT prolongation and Torsades de Pointes (observed in patients who developed hypokalemia or had underlying cardiovascular conditions). Immune System Disorders – Hypersensitivity: anaphylactic reactions (severe allergic reactions that include, but are not limited to difficulty swallowing or breathing, swollen face, lips, tongue or throat, or an itchy rash (urticaria)).

<table ID="ID192" width="100%"><caption>Table 1: Adverse Reactions due to Abiraterone Acetate Tablets in COU-AA-301</caption><col width="45%"/><col width="14%"/><col width="13%"/><col width="14%"/><col width="13%"/><tfoot><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">¹Adverse events graded according to CTCAE version 3. </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">²Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">³Includes terms Muscle spasms, Musculoskeletal pain, Myalgia, Musculoskeletal discomfort, and Musculoskeletal stiffness. </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">⁴Includes terms Edema, Edema peripheral, Pitting edema, and Generalized edema. </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">⁵Includes all fractures with the exception of pathological fracture. </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">⁶Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia. </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">⁷Includes terms Angina pectoris, Chest pain, and Angina unstable. Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the abiraterone acetate tablets arm (1.3% vs. 1.1% respectively). </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">⁸Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased. </paragraph></td></tr></tfoot><tbody><tr><td styleCode="Lrule Toprule Rrule" valign="top"/><td colspan="2" align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Abiraterone Acetate Tablets with Prednisone</content> </td><td colspan="2" align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Placebo with Prednisone</content> </td></tr><tr><td styleCode="Lrule Botrule Rrule" valign="top"/><td colspan="2" align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">(N=791)</content> </td><td colspan="2" align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">(N=394)</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">System/Organ Class</content> </td><td align="center" styleCode=" Botrule Rrule" valign="top">All Grades ¹ </td><td align="center" styleCode=" Botrule Rrule" valign="top">Grade 3 to 4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">All Grades </td><td align="center" styleCode=" Botrule Rrule" valign="top">Grade 3 to 4 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Adverse reaction </td><td align="center" styleCode=" Botrule Rrule" valign="top">% </td><td align="center" styleCode=" Botrule Rrule" valign="top">% </td><td align="center" styleCode=" Botrule Rrule" valign="top">% </td><td align="center" styleCode=" Botrule Rrule" valign="top">% </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Joint swelling/discomfort ² </td><td align="center" styleCode=" Botrule Rrule" valign="top">30 </td><td align="center" styleCode=" Botrule Rrule" valign="top">4.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">23 </td><td align="center" styleCode=" Botrule Rrule" valign="top">4.1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Muscle discomfort ³ </td><td align="center" styleCode=" Botrule Rrule" valign="top">26 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">23 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">General disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Edema ⁴ </td><td align="center" styleCode=" Botrule Rrule" valign="top">27 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">18 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.8 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Vascular disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Hot flush </td><td align="center" styleCode=" Botrule Rrule" valign="top">19 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">17 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Hypertension </td><td align="center" styleCode=" Botrule Rrule" valign="top">8.5 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">6.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Diarrhea </td><td align="center" styleCode=" Botrule Rrule" valign="top">18 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">14 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Dyspepsia </td><td align="center" styleCode=" Botrule Rrule" valign="top">6.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Infections and infestations</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Urinary tract infection </td><td align="center" styleCode=" Botrule Rrule" valign="top">12 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">7.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.5 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Upper respiratory tract infection </td><td align="center" styleCode=" Botrule Rrule" valign="top">5.4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.5 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Cough </td><td align="center" styleCode=" Botrule Rrule" valign="top">11 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">7.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Renal and urinary disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Urinary frequency </td><td align="center" styleCode=" Botrule Rrule" valign="top">7.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">5.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Nocturia </td><td align="center" styleCode=" Botrule Rrule" valign="top">6.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">4.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Injury, poisoning and procedural complications</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Fractures ⁵ </td><td align="center" styleCode=" Botrule Rrule" valign="top">5.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Cardiac disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Arrhythmia ⁶ </td><td align="center" styleCode=" Botrule Rrule" valign="top">7.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">4.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Chest pain or chest discomfort ⁷ </td><td align="center" styleCode=" Botrule Rrule" valign="top">3.8 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.5 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.8 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Cardiac failure ⁸ </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.3 </td></tr></tbody></table>

<table ID="ID194" width="100%"><caption>Table 2: Laboratory Abnormalities of Interest in COU-AA-301</caption><col width="29%"/><col width="17%"/><col width="17%"/><col width="17%"/><col width="17%"/><tbody><tr><td styleCode="Lrule Toprule Rrule" valign="top"/><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Abiraterone Acetate Tablets with Prednisone</content> <content styleCode="bold">(N=791)</content> </td><td colspan="2" align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Placebo</content> <content styleCode="bold">with Prednisone</content> <content styleCode="bold">(N=394)</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Laboratory Abnormality </td><td align="center" styleCode=" Botrule Rrule" valign="top">All Grades (%) </td><td align="center" styleCode=" Toprule Botrule Rrule" valign="top">Grade 3 to 4 (%) </td><td align="center" styleCode=" Botrule Rrule" valign="top">All Grades (%) </td><td align="center" styleCode=" Botrule Rrule" valign="top">Grade 3 to 4 (%) </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="bottom">Hypertriglyceridemia </td><td align="center" styleCode=" Botrule Rrule" valign="top">63 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">53 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">High AST </td><td align="center" styleCode=" Botrule Rrule" valign="top">31 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">36 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.5 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Hypokalemia </td><td align="center" styleCode=" Botrule Rrule" valign="top">28 </td><td align="center" styleCode=" Botrule Rrule" valign="top">5.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">20 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">Hypophosphatemia </td><td align="center" styleCode=" Botrule Rrule" valign="top">24 </td><td align="center" styleCode=" Botrule Rrule" valign="top">7.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">16 </td><td align="center" styleCode=" Botrule Rrule" valign="top">5.8 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">High ALT </td><td align="center" styleCode=" Botrule Rrule" valign="top">11 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">10 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.8 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top">High Total Bilirubin </td><td align="center" styleCode=" Botrule Rrule" valign="top">6.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">4.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr></tbody></table>

<table ID="ID196" width="100%"><caption>Table 3: Adverse Reactions in &#x2265;5% of Patients on the Abiraterone Acetate Tablets Arm in COU-AA-302</caption><col width="38%"/><col width="16%"/><col width="15%"/><col width="14%"/><col width="14%"/><tfoot><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">¹Adverse events graded according to CTCAE version 3. </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">²Includes terms Edema peripheral, Pitting edema, and Generalized edema. </paragraph></td></tr><tr><td align="left" colspan="5"><paragraph styleCode="Footnote">³Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness. </paragraph></td></tr></tfoot><tbody><tr><td styleCode="Lrule Toprule Rrule" valign="top"/><td colspan="2" align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Abiraterone Acetate Tablets with Prednisone</content> </td><td colspan="2" align="center" styleCode=" Toprule Rrule" valign="top"><content styleCode="bold">Placebo with Prednisone</content> </td></tr><tr><td styleCode=" Lrule Rrule" valign="top"/><td colspan="2" align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">(N=542)</content> </td><td colspan="2" align="center" styleCode=" Botrule Rrule" valign="top"><content styleCode="bold">(N=540)</content> </td></tr><tr><td align="left" styleCode=" Lrule Rrule" valign="top"><content styleCode="bold">System/Organ Class</content> Adverse reaction </td><td align="center" styleCode=" Rrule" valign="top">All Grades ¹ </td><td align="center" styleCode=" Toprule Rrule" valign="top">Grade 3 to 4 </td><td align="center" styleCode=" Rrule" valign="top">All Grades </td><td align="center" styleCode=" Rrule" valign="top">Grade 3 to 4 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> </td><td align="center" styleCode=" Botrule Rrule" valign="top">% </td><td align="center" styleCode=" Botrule Rrule" valign="top">% </td><td align="center" styleCode=" Botrule Rrule" valign="top">% </td><td align="center" styleCode=" Botrule Rrule" valign="top">% </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">General disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Fatigue </td><td align="center" styleCode=" Botrule Rrule" valign="top">39 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">34 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.7 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Edema ² </td><td align="center" styleCode=" Botrule Rrule" valign="top">25 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">21 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Pyrexia </td><td align="center" styleCode=" Botrule Rrule" valign="top">8.7 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">5.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Joint swelling/discomfort ³ </td><td align="center" styleCode=" Botrule Rrule" valign="top">30 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">25 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Groin pain </td><td align="center" styleCode=" Botrule Rrule" valign="top">6.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">4.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.7 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Constipation </td><td align="center" styleCode=" Botrule Rrule" valign="top">23 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">19 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.6 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Diarrhea </td><td align="center" styleCode=" Botrule Rrule" valign="top">22 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">18 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.9 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Dyspepsia </td><td align="center" styleCode=" Botrule Rrule" valign="top">11 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">5 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Vascular disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Hot flush </td><td align="center" styleCode=" Botrule Rrule" valign="top">22 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">18 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Hypertension </td><td align="center" styleCode=" Botrule Rrule" valign="top">22 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">13 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Cough </td><td align="center" styleCode=" Botrule Rrule" valign="top">17 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">14 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Dyspnea </td><td align="center" styleCode=" Botrule Rrule" valign="top">12 </td><td align="center" styleCode=" Botrule Rrule" valign="top">2.4 </td><td align="center" styleCode=" Botrule Rrule" valign="top">9.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.9 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Psychiatric disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Insomnia </td><td align="center" styleCode=" Botrule Rrule" valign="top">14 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.2 </td><td align="center" styleCode=" Botrule Rrule" valign="top">11 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Injury, poisoning and procedural complications</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Contusion </td><td align="center" styleCode=" Botrule Rrule" valign="top">13 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">9.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Falls </td><td align="center" styleCode=" Botrule Rrule" valign="top">5.9 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Infections and infestations</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Upper respiratory tract infection </td><td align="center" styleCode=" Botrule Rrule" valign="top">13 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">8 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Nasopharyngitis </td><td align="center" styleCode=" Botrule Rrule" valign="top">11 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">8.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Renal and urinary disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Hematuria </td><td align="center" styleCode=" Botrule Rrule" valign="top">10 </td><td align="center" styleCode=" Botrule Rrule" valign="top">1.3 </td><td align="center" styleCode=" Botrule Rrule" valign="top">5.6 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0.6 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Skin and subcutaneous tissue disorders</content> </td><td colspan="4" styleCode=" Botrule Rrule" valign="top"/></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"> Rash </td><td align="center" styleCode=" Botrule Rrule" valign="top">8.1 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td><td align="center" styleCode=" Botrule Rrule" valign="top">3.7 </td><td align="center" styleCode=" Botrule Rrule" valign="top">0 </td></tr></tbody></table>