Unituxin

WARNING: SERIOUS INFUSION REACTIONS AND NEUROTOXICITY WARNING: SERIOUS INFUSION REACTIONS AND NEUROTOXICITY See full prescribing information for complete boxed warning. Infusion Reactions: Life-threatening infusion adverse reactions occur with Unituxin. Administer required prehydration and premedication. Immediately interrupt for severe infusion reactions and permanently discontinue for anaphylaxis [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.1) ] . Neurotoxicity: Unituxin causes severe neuropathic pain. Administer intravenous opioid prior to, during, and for 2 hours following completion of the Unituxin infusion. Severe peripheral sensory neuropathy ranged from 2% to 9% in patients with neuroblastoma. Severe peripheral motor neuropathy has also been reported. Discontinue for severe unresponsive pain, severe sensory neuropathy, and moderate to severe peripheral motor neuropathy [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.2) ] . Infusion Reactions Serious and potentially life-threatening infusion reactions occurred in 26% of patients treated with Unituxin. Administer required prehydration and premedication including antihistamines prior to each Unituxin infusion. Monitor patients closely for signs and symptoms of an infusion reaction during and for at least four hours following completion of each Unituxin infusion. Immediately interrupt Unituxin for severe infusion reactions and permanently discontinue Unituxin for anaphylaxis ( 2.2, 2.3, 5.1 ). Neurotoxicity Unituxin causes serious neurologic adverse reactions including severe neuropathic pain and peripheral neuropathy. Severe neuropathic pain occurs in the majority of patients. Administer intravenous opioid prior to, during, and for 2 hours following completion of the Unituxin infusion. In clinical studies of patients with high-risk neuroblastoma, Grade 3 peripheral sensory neuropathy occurred in 2% to 9% of patients. In clinical studies of Unituxin and related GD2-binding antibodies, severe motor neuropathy has occurred. Resolution of motor neuropathy did not occur in all cases. Discontinue Unituxin for severe unresponsive pain, severe sensory neuropathy, and moderate to severe peripheral motor neuropathy ( 2.2, 2.3, 5.2 ).

5 WARNINGS AND PRECAUTIONS Neurological Disorders of the Eye: Interrupt Unituxin for dilated pupil with sluggish light reflex or other visual disturbances and permanently discontinue Unituxin for recurrent eye disorders or loss of vision. ( 5.2 ) Prolonged Urinary Retention and Transverse Myelitis: Permanently discontinue Unituxin and institute supportive care. ( 5.2 ) Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Permanently discontinue Unituxin and institute supportive care for signs and symptoms of RPLS. ( 5.2 ) Capillary Leak Syndrome and Hypotension: Administer required prehydration and monitor patients closely during treatment. Depending upon severity, manage by interruption, infusion rate reduction, or permanent discontinuation. ( 5.3 , 5.4 ) Infection: Interrupt until resolution of systemic infection. ( 5.5 ) Bone Marrow Suppression: Monitor peripheral blood counts during Unituxin therapy. ( 5.6 ) Electrolyte Abnormalities: Monitor serum electrolytes closely. ( 5.7 ) Atypical Hemolytic Uremic Syndrome: Permanently discontinue Unituxin and institute supportive management. ( 5.8 ) Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. ( 5.9 , 8.1 , 8.3 ) 5.1 Serious Infusion Reactions Serious infusion reactions requiring urgent intervention, including blood pressure support, bronchodilator therapy, corticosteroids, infusion rate reduction, infusion interruption, or permanent discontinuation of Unituxin, included facial and upper airway edema, dyspnea, bronchospasm, stridor, urticaria, and hypotension. Infusion reactions generally occurred during or within 24 hours of completing the Unituxin infusion. Due to overlapping signs and symptoms, it was not possible to distinguish between infusion reactions and hypersensitivity reactions in some cases. In Study 1, Severe (Grade 3 or 4) infusion reactions occurred in 35 (26%) patients in the Unituxin/13-cis-retinoic acid (RA) group compared to 1 (1%) patient receiving RA alone. Severe urticaria occurred in 17 (13%) patients in the Unituxin/RA group but did not occur in the RA group. Serious adverse reactions consistent with anaphylaxis and resulting in permanent discontinuation of Unituxin occurred in 2 (1%) patients in the Unituxin/RA group. Additionally, 1 (0.1%) patient had multiple cardiac arrests and died within 24 hours after having received Unituxin in Study 2. Prior to each Unituxin dose, administer required intravenous hydration and premedication with antihistamines, analgesics, and antipyretics [see Dosage and Administration (2.2) ] . Monitor patients closely for signs and symptoms of infusion reactions during and for at least 4 hours following completion of each Unituxin infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. For mild to moderate infusion reactions, such as transient rash, fever, rigors, and localized urticaria, that respond promptly to antihistamines or antipyretics, decrease the Unituxin infusion rate and monitor closely. Immediately interrupt or permanently discontinue Unituxin and institute supportive management for severe or prolonged infusion reactions. Permanently discontinue Unituxin and institute supportive management for life-threatening infusion reactions [see Dosage and Administration (2.3) ] . 5.2 Neurotoxicity Pain In Study 1, 114 (85%) patients treated in the Unituxin/RA group experienced pain despite pre-treatment with analgesics, including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients in the Unituxin/RA group compared to 5 (5%) patients in the RA group. Pain typically occurred during the Unituxin infusion and was most commonly reported as abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, and arthralgia. Premedicate with analgesics, including intravenous opioids, prior to each dose of Unituxin and continue analgesics until 2 hours following completion of Unituxin [see Dosage and Administration (2.2) ] . For severe pain, decrease the Unituxin infusion rate to 0.875 mg/m 2 /hour. Discontinue Unituxin if pain is not adequately controlled despite infusion rate reduction and institution of maximum supportive measures [see Dosage and Administration (2.3) ] . Peripheral Neuropathy In Study 1, severe (Grade 3) peripheral sensory neuropathy occurred in 2 (1%) patients and severe peripheral motor neuropathy occurred in 2 (1%) patients in the Unituxin/RA group. No patients treated with RA alone experienced severe peripheral neuropathy. The duration and reversibility of peripheral neuropathy occurring in Study 1 was not documented. In Study 3, no patients experienced peripheral motor neuropathy. Among the 9 (9%) patients who experienced peripheral sensory neuropathy of any severity, the median (min, max) duration of peripheral sensory neuropathy was 9 (3, 163) days. In a study of a related anti-GD2 antibody conducted in 12 adult patients with metastatic melanoma, 2 (13%) patients developed severe motor neuropathy. One patient developed lower extremity weakness and inability to ambulate that persisted for approximately 6 weeks. Another patient developed severe lower extremity weakness resulting in an inability to ambulate without assistance that lasted for approximately 16 weeks and neurogenic bladder that lasted for approximately 3 weeks. Complete resolution of motor neuropathy was not documented in this case. Permanently discontinue Unituxin in patients with peripheral motor neuropathy of Grade 2 or greater severity, Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks, or Grade 4 sensory neuropathy [see Dosage and Administration (2.3) ] . Neurological Disorders of the Eye Neurological disorders of the eye experienced by 2 or more patients treated with Unituxin in Studies 1, 2, or 3 included blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, eyelid ptosis, and papilledema. In Study 1, 3 (2%) patients in the Unituxin/RA group experienced blurred vision, compared to no patients in the RA group. Diplopia, mydriasis, and unequal pupillary size occurred in 1 patient each in the Unituxin/RA group, compared to no patients in the RA group. The duration of eye disorders occurring in Study 1 was not documented. In Study 3, eye disorders occurred in 16 (15%) patients, and in 3 (3%) patients resolution of the eye disorder was not documented. Among the cases with documented resolution, the median duration of eye disorders was 4 days (range: 0, 221 days). Interrupt Unituxin in patients experiencing dilated pupil with sluggish light reflex or other visual disturbances that do not cause visual loss. Upon resolution and if continued treatment with Unituxin is warranted, decrease the Unituxin dose by 50%. Permanently discontinue Unituxin in patients with recurrent signs or symptoms of an eye disorder following dose reduction and in patients who experience loss of vision [see Dosage and Administration (2.3) ] . Prolonged Urinary Retention Urinary retention that persists for weeks to months following discontinuation of opioids has occurred in patients treated with Unituxin. Permanently discontinue Unituxin in patients with urinary retention that does not resolve following discontinuation of opioids [see Dosage and Administration (2.3) and Postmarketing Experience (6.2) ] . Transverse Myelitis Transverse myelitis has occurred in patients treated with Unituxin. Promptly evaluate any patient with signs or symptoms of transverse myelitis, such as weakness, paresthesia, sensory loss, or incontinence. Permanently discontinue Unituxin in patients who develop transverse myelitis [see Dosage and Administration (2.3) and Postmarketing Experience (6.2) ] . Reversible Posterior Leukoencephalopathy Syndrome Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has occurred in patients treated with Unituxin. Institute appropriate medical treatment and permanently discontinue Unituxin in patients with signs and symptoms of RPLS (eg, severe headache, hypertension, visual changes, lethargy, or seizures) [see Dosage and Administration (2.3) and Postmarketing Experience (6.2) ] . 5.3 Capillary Leak Syndrome In Study 1, severe (Grade 3 to 5) capillary leak syndrome occurred in 31 (23%) patients in the Unituxin/RA group and in no patients treated with RA alone. Additionally, capillary leak syndrome was reported as a serious adverse reaction in 9 (6%) patients in the Unituxin/RA group and in no patients treated with RA alone. Immediately interrupt or discontinue Unituxin and institute supportive management in patients with symptomatic or severe capillary leak syndrome [see Dosage and Administration (2.3) ] . 5.4 Hypotension In Study 1, severe (Grade 3 or 4) hypotension occurred in 22 (16%) patients in the Unituxin/RA group compared to no patients in the RA group. Prior to each Unituxin infusion, administer required intravenous hydration. Closely monitor blood pressure during Unituxin treatment. Immediately interrupt or discontinue Unituxin and institute supportive management in patients with symptomatic hypotension, systolic blood pressure (SBP) less than lower limit of normal for age, or SBP that is decreased by more than 15% compared to baseline [see Dosage and Administration (2.2 , 2.3) ] . 5.5 Infection In Study 1, severe (Grade 3 or 4) bacteremia requiring intravenous antibiotics or other urgent intervention occurred in 17 (13%) patients in the Unituxin/RA group compared to 5 (5%) patients treated with RA alone. Sepsis occurred in 24 (18%) patients in the Unituxin/RA group and in 10 (9%) patients in the RA group. Monitor patients closely for signs and symptoms of systemic infection and temporarily discontinue Unituxin in patients who develop systemic infection until resolution of the infection [see Dosage and Administration (2.3) ] . 5.6 Bone Marrow Suppression In Study 1, severe (Grade 3 or 4) thrombocytopenia (39% vs. 25%), anemia (34% vs. 16%), neutropenia (34% vs. 13%), and febrile neutropenia (4% vs. 0 patients) occurred more commonly in patients in the Unituxin/RA group compared to patients treated with RA alone. Monitor peripheral blood counts closely during therapy with Unituxin. 5.7 Electrolyte Abnormalities In Study 1, electrolyte abnormalities occurring in at least 25% of patients who received Unituxin/RA included hyponatremia, hypokalemia, and hypocalcemia. Severe (Grade 3 or 4) hypokalemia and hyponatremia occurred in 37% and 23% of patients in the Unituxin/RA group, respectively, compared to 2% and 4% of patients in the RA group. In a study of a related anti-GD2 antibody conducted in 12 adult patients with metastatic melanoma, 2 (13%) patients developed syndrome of inappropriate antidiuretic hormone secretion resulting in severe hyponatremia. Monitor serum electrolytes daily during therapy with Unituxin. 5.8 Atypical Hemolytic Uremic Syndrome Hemolytic uremic syndrome in the absence of documented infection and resulting in renal insufficiency, electrolyte abnormalities, anemia, and hypertension occurred in 2 patients enrolled in Study 2 following receipt of the first cycle of Unituxin. Atypical hemolytic uremic syndrome recurred following rechallenge with Unituxin in 1 patient. Permanently discontinue Unituxin and institute supportive management for signs of hemolytic uremic syndrome [see Dosage and Administration (2.3) ] . 5.9 Embryo-Fetal Toxicity Based on its mechanism of action, Unituxin may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for 2 months after the last dose of Unituxin [see Use in Specific Populations (8.1 , 8.3) and Clinical Pharmacology (12.1) ] .

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Serious Infusion Reactions [see Boxed Warning and Warnings and Precautions (5.1) ] Neurotoxicity, including Pain, Peripheral Neuropathy, Neurological Disorders of the Eye, Prolonged Urinary Retention, Transverse Myelitis, and Reversible Posterior Leukoencephalopathy Syndrome [see Boxed Warning and Warnings and Precautions (5.2) ] Capillary Leak Syndrome [see Warnings and Precautions (5.3) ] Hypotension [see Warnings and Precautions (5.4) ] Infection [see Warnings and Precautions (5.5) ] Bone Marrow Suppression [see Warnings and Precautions (5.6) ] Electrolyte Abnormalities [see Warnings and Precautions (5.7) ] Atypical Hemolytic Uremic Syndrome [see Warnings and Precautions (5.8) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.9) ] The most common adverse drug reactions (≥25%) are pain, pyrexia, thrombocytopenia, lymphopenia, infusion reactions, hypotension, hyponatremia, increased alanine aminotransferase, anemia, vomiting, diarrhea, hypokalemia, capillary leak syndrome, neutropenia, urticaria, hypoalbuminemia, increased aspartate aminotransferase, and hypocalcemia. ( 5 , 6.1 ) The most common serious adverse reactions (≥5%) are infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome. ( 5 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact United Therapeutics Corp. at 1-866-458-6479 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 rates observed in clinical practice. The data described below reflect exposure to Unituxin at the recommended dose and schedule in 1021 patients with high-risk neuroblastoma enrolled in an open-label, randomized (Study 1), or single-arm clinical trials (Study 2 and Study 3). Prior to enrollment, patients received therapy consisting of induction combination chemotherapy, maximum feasible surgical resection, myeloablative consolidation chemotherapy followed by autologous stem cell transplant, and radiation therapy to residual soft tissue disease. Patients received Unituxin in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA). Treatment commenced within 95 days post autologous stem cell transplant in Study 1, within 210 days of autologous stem cell transplant in Study 2, and within 110 days of autologous stem cell transplant in Study 3. Study 1 In a randomized, open-label, multicenter study (Study 1), 134 patients received Unituxin in combination with GM-CSF, IL-2, and RA (Unituxin/RA group), including 109 randomized patients and 25 patients with biopsy-proven residual disease who were non-randomly assigned to receive Unituxin. A total of 106 randomized patients received RA alone (RA group) [see Dosage and Administration (2) and Clinical Studies (14) ] . Patients had a median age at enrollment of 3.8 years (range: 0.94 to 15.3 years), and were predominantly male (60%) and White (82%). In Study 1, adverse reactions of Grade 3 or greater severity were comprehensively collected, but adverse reactions of Grade 1 or 2 severity were collected sporadically and laboratory data were not comprehensively collected. Approximately 71% of patients in the Unituxin/RA group and 77% of patients in the RA group completed planned treatment. The most common reason for premature discontinuation of study therapy was adverse reactions in the Unituxin/RA group (19%) and progressive disease (17%) in the RA group. The most common adverse drug reactions (≥25%) in the Unituxin/RA group were pain, pyrexia, thrombocytopenia, lymphopenia, infusion reactions, hypotension, hyponatremia, increased alanine aminotransferase, anemia, vomiting, diarrhea, hypokalemia, capillary leak syndrome, neutropenia, urticaria, hypoalbuminemia, increased aspartate aminotransferase, and hypocalcemia. The most common serious adverse reactions (≥5%) in the Unituxin/RA group were infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome. Table 5 lists the adverse reactions reported in at least 10% of patients in the Unituxin/RA group for which there was a between group difference of at least 5% (all grades) or 2% (Grade 3 or greater severity). Table 5: Selected Adverse Reactions Occurring in at Least 10% of Patients in the Unituxin/RA Group in Study 1 Adverse Reaction Includes adverse reactions that occurred in at least 10% of patients in the Unituxin/RA group with at least a 5% (All Grades) or 2% (Grades 3 to 5) absolute higher incidence in the Unituxin/RA group compared to the RA group. , Adverse drug reactions were graded using CTCAE version 3.0. Unituxin/RA (N=134) RA (N=106) All Grades (%) Grades 3 to 4 (%) All Grades (%) Grades 3 to 4 (%) General Disorders and Administration Site Conditions Pain Includes preferred terms abdominal pain, abdominal pain upper, arthralgia, back pain, bladder pain, bone pain, chest pain, facial pain, gingival pain, infusion related reaction, musculoskeletal chest pain, myalgia, neck pain, neuralgia, oropharyngeal pain, pain, pain in extremity, and proctalgia. 85 51 16 6 Pyrexia 72 40 27 6 Edema 17 0 0 0 Blood and Lymphatic System Disorders Based on investigator reported adverse reactions. Thrombocytopenia 66 39 43 25 Lymphopenia 62 51 36 20 Anemia 51 34 22 16 Neutropenia 39 34 16 13 Immune System Disorders Infusion reactions 60 25 9 1 Vascular Disorders Hypotension 60 16 3 0 Capillary leak syndrome One Grade 5 adverse reaction. 40 23 1 0 Hemorrhage Includes preferred terms gastrointestinal hemorrhage, hematochezia, rectal hemorrhage, hematemesis, upper gastrointestinal hemorrhage, hematuria, hemorrhage urinary tract, renal hemorrhage, epistaxis, respiratory tract hemorrhage, disseminated intravascular coagulation, catheter site hemorrhage, hemorrhage, and hematoma. 17 6 6 3 Hypertension 14 2 7 1 Metabolism and Nutrition Disorders Hyponatremia 58 23 12 4 Hypokalemia 43 37 4 2 Hypoalbuminemia 33 7 3 0 Hypocalcemia 27 7 0 0 Hypophosphatemia 20 8 3 0 Hyperglycemia 18 6 4 1 Hypertriglyceridemia 16 1 11 1 Decreased appetite 15 10 5 4 Hypomagnesemia 12 2 1 0 Investigations Increased alanine aminotransferase 56 23 31 3 Increased aspartate aminotransferase 28 10 7 0 Increased serum creatinine 15 2 6 0 Increased weight 10 0 0 0 Gastrointestinal Disorders Vomiting 46 6 19 3 Diarrhea 43 13 15 1 Nausea 10 2 3 1 Skin and Subcutaneous Tissue Disorders Urticaria 37 13 3 0 Respiratory, Thoracic and Mediastinal Disorders Hypoxia 24 12 2 1 Cardiac Disorders Tachycardia Includes preferred terms tachycardia and sinus tachycardia. 19 2 1 0 Infections and Infestations Sepsis 18 16 9 9 Device related infection 16 16 11 11 Renal and Urinary Disorders Proteinuria 16 0 3 1 Nervous System Disorders Peripheral neuropathy 13 3 6 0 Table 6 compares the per-patient incidence of selected adverse reactions occurring during cycles containing Unituxin in combination with GM-CSF (Cycles 1, 3, and 5) with cycles containing Unituxin in combination with IL-2 (Cycles 2 and 4). Table 6: Comparison of Adverse Events by Treatment Cycle in the Unituxin/RA Group in Study 1 Preferred Term Includes preferred terms with a per-patient incidence of at least 20% in the Unituxin and RA group for either IL-2 or GM-CSF containing cycles. , Adverse drug reactions were graded using CTCAE version 3.0. All Grades Severe GM-CSF N=134 (%) IL-2 Seven patients who received GM-CSF in Cycle 1 discontinued prior to starting Cycle 2. N=127 (%) GM-CSF N=134 (%) IL-2 N=127 (%) GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-2, interleukin-2; RA, 13-cis-retinoic acid General Disorders and administration site conditions Pyrexia 55 65 10 37 Pain Includes preferred terms abdominal pain, abdominal pain upper, arthralgia, back pain, bladder pain, bone pain, chest pain, facial pain, gingival pain, infusion related reaction, musculoskeletal chest pain, myalgia, neck pain, neuralgia, oropharyngeal pain, pain, pain in extremity, and proctalgia. 77 61 43 35 Blood and Lymphatic System Disorders Based on investigator-reported adverse reactions. Thrombocytopenia 62 61 31 33 Lymphopenia 54 61 33 50 Anemia 42 42 21 24 Neutropenia 25 32 19 28 Immune System Disorders Infusion reactions 47 54 10 20 Vascular Disorders Hypotension 43 54 5 16 Capillary leak syndrome 22 36 11 20 Metabolism and Nutrition Disorders Hyponatremia 36 55 5 21 Hypokalemia 26 39 13 33 Hypoalbuminemia 29 29 3 5 Hypocalcemia 20 21 2 6 Investigations Increased alanine aminotransferase 43 48 15 13 Aspartate aminotransferase increased 16 21 4 7 Gastrointestinal Disorders Diarrhea 31 37 6 13 Vomiting 33 35 3 2 Skin and Subcutaneous Tissue Disorders Urticaria 25 29 7 7 Study 2 and Study 3 Study 2 was a single-arm, multicenter, expanded access trial that enrolled patients with high-risk neuroblastoma (N=783). The reported adverse event profile of Unituxin in Study 2 was similar to that observed in Study 1. Study 3 was a multicenter, single-arm safety study of Unituxin in combination with GM-CSF, IL-2, and RA. In Study 3, adverse events of all CTCAE grades and laboratory data were systematically and comprehensively collected. Of 104 patients enrolled and treated in Study 3, 77% of patients completed study therapy. In general, the adverse reaction profile of Unituxin observed in Study 3 was similar to that observed in Study 1 and Study 2. The following adverse reactions not previously reported in Study 1 were reported in at least 10% of patients in Study 3: nasal congestion (20%) and wheezing (15%). Table 7 provides the per-patient incidence of laboratory abnormalities in Study 3. Table 7: Per-patient Incidence of Selected (≥5% Grade 3 to 4) Laboratory Abnormalities in Study 3 Laboratory Test Laboratory abnormalities with a per-patient incidence of at least 20% (all grades) and at least a 5% per-patient incidence of severe (Grade 3 or 4) laboratory abnormalities. Grade Based on CTCAE version 4.0. All Grades % Grades 3 to 4 % ND, not determined Hematology Anemia 100 46 Neutropenia 99 63 Thrombocytopenia 98 49 Chemistry Hypoalbuminemia 100 8 Hypocalcemia 97 7 Hyponatremia 93 36 Hyperglycemia 87 6 Aspartate Aminotransferase Increased 84 8 Alanine Aminotransferase Increased 83 13 Hypokalemia 82 41 Hypophosphatemia 78 6 Urinalysis Urinalysis results were reported as positive or negative without assessment of grade. Urine protein 66 ND Red blood cell casts 38 ND 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Unituxin. 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. Neurotoxicity: prolonged urinary retention, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.2) ] .

<table width="90%"><caption>Table 5: Selected Adverse Reactions Occurring in at Least 10% of Patients in the Unituxin/RA Group in Study 1</caption><col width="36%" align="left" valign="top"/><col width="16%" align="center" valign="top"/><col width="16%" align="center" valign="top"/><col width="16%" align="center" valign="top"/><col width="16%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule" rowspan="2" align="center" valign="bottom">Adverse Reaction<footnote>Includes adverse reactions that occurred in at least 10% of patients in the Unituxin/RA group with at least a 5% (All Grades) or 2% (Grades 3 to 5) absolute higher incidence in the Unituxin/RA group compared to the RA group.</footnote>^,<footnote>Adverse drug reactions were graded using CTCAE version 3.0.</footnote></th><th styleCode="Rrule Botrule" colspan="2">Unituxin/RA (N=134)</th><th styleCode="Rrule Botrule" colspan="2">RA (N=106)</th></tr><tr><th styleCode="Rrule" align="center">All Grades (%)</th><th styleCode="Rrule">Grades 3 to 4 (%)</th><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grades 3 to 4 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">General Disorders and Administration Site Conditions</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pain<footnote>Includes preferred terms abdominal pain, abdominal pain upper, arthralgia, back pain, bladder pain, bone pain, chest pain, facial pain, gingival pain, infusion related reaction, musculoskeletal chest pain, myalgia, neck pain, neuralgia, oropharyngeal pain, pain, pain in extremity, and proctalgia.</footnote></td><td styleCode="Rrule">85</td><td styleCode="Rrule">51</td><td styleCode="Rrule">16</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pyrexia</td><td styleCode="Rrule">72</td><td styleCode="Rrule">40</td><td styleCode="Rrule">27</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Edema</td><td styleCode="Rrule">17</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Blood and Lymphatic System Disorders</content><footnote ID="t5f4">Based on investigator reported adverse reactions.</footnote></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Thrombocytopenia</td><td styleCode="Rrule">66</td><td styleCode="Rrule">39</td><td styleCode="Rrule">43</td><td styleCode="Rrule">25</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Lymphopenia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">62</td><td styleCode="Rrule">51</td><td styleCode="Rrule">36</td><td styleCode="Rrule">20</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Anemia</td><td styleCode="Rrule">51</td><td styleCode="Rrule">34</td><td styleCode="Rrule">22</td><td styleCode="Rrule">16</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Neutropenia</td><td styleCode="Rrule">39</td><td styleCode="Rrule">34</td><td styleCode="Rrule">16</td><td styleCode="Rrule">13</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Immune System Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Infusion reactions</td><td styleCode="Rrule">60</td><td styleCode="Rrule">25</td><td styleCode="Rrule">9</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Vascular Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypotension</td><td styleCode="Rrule">60</td><td styleCode="Rrule">16</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Capillary leak syndrome<footnote>One Grade 5 adverse reaction.</footnote></td><td styleCode="Rrule">40</td><td styleCode="Rrule">23</td><td styleCode="Rrule">1</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hemorrhage<footnote>Includes preferred terms gastrointestinal hemorrhage, hematochezia, rectal hemorrhage, hematemesis, upper gastrointestinal hemorrhage, hematuria, hemorrhage urinary tract, renal hemorrhage, epistaxis, respiratory tract hemorrhage, disseminated intravascular coagulation, catheter site hemorrhage, hemorrhage, and hematoma.</footnote></td><td styleCode="Rrule">17</td><td styleCode="Rrule">6</td><td styleCode="Rrule">6</td><td styleCode="Rrule">3</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypertension</td><td styleCode="Rrule">14</td><td styleCode="Rrule">2</td><td styleCode="Rrule">7</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Metabolism and Nutrition Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyponatremia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">58</td><td styleCode="Rrule">23</td><td styleCode="Rrule">12</td><td styleCode="Rrule">4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypokalemia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">43</td><td styleCode="Rrule">37</td><td styleCode="Rrule">4</td><td styleCode="Rrule">2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypoalbuminemia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">33</td><td styleCode="Rrule">7</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypocalcemia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">27</td><td styleCode="Rrule">7</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypophosphatemia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">20</td><td styleCode="Rrule">8</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyperglycemia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">18</td><td styleCode="Rrule">6</td><td styleCode="Rrule">4</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypertriglyceridemia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">16</td><td styleCode="Rrule">1</td><td styleCode="Rrule">11</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Decreased appetite</td><td styleCode="Rrule">15</td><td styleCode="Rrule">10</td><td styleCode="Rrule">5</td><td styleCode="Rrule">4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypomagnesemia<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">12</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Investigations</content></td></tr><tr styleCode="Botrule"><td valign="middle" styleCode="Lrule Rrule"> Increased alanine aminotransferase<footnoteRef IDREF="t5f4"/></td><td valign="middle" styleCode="Rrule">56</td><td valign="middle" styleCode="Rrule">23</td><td valign="middle" styleCode="Rrule">31</td><td valign="middle" styleCode="Rrule">3</td></tr><tr styleCode="Botrule"><td valign="middle" styleCode="Lrule Rrule"> Increased aspartate aminotransferase<footnoteRef IDREF="t5f4"/></td><td valign="middle" styleCode="Rrule">28</td><td valign="middle" styleCode="Rrule">10</td><td valign="middle" styleCode="Rrule">7</td><td valign="middle" styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Increased serum creatinine<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">15</td><td styleCode="Rrule">2</td><td styleCode="Rrule">6</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Increased weight</td><td styleCode="Rrule">10</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Gastrointestinal Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">46</td><td styleCode="Rrule">6</td><td styleCode="Rrule">19</td><td styleCode="Rrule">3</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Diarrhea</td><td styleCode="Rrule">43</td><td styleCode="Rrule">13</td><td styleCode="Rrule">15</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nausea</td><td styleCode="Rrule">10</td><td styleCode="Rrule">2</td><td styleCode="Rrule">3</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Urticaria</td><td styleCode="Rrule">37</td><td styleCode="Rrule">13</td><td styleCode="Rrule">3</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Respiratory, Thoracic and Mediastinal Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypoxia</td><td styleCode="Rrule">24</td><td styleCode="Rrule">12</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Cardiac Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Tachycardia<footnote>Includes preferred terms tachycardia and sinus tachycardia.</footnote></td><td styleCode="Rrule">19</td><td styleCode="Rrule">2</td><td styleCode="Rrule">1</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Infections and Infestations</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Sepsis</td><td styleCode="Rrule">18</td><td styleCode="Rrule">16</td><td styleCode="Rrule">9</td><td styleCode="Rrule">9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Device related infection</td><td styleCode="Rrule">16</td><td styleCode="Rrule">16</td><td styleCode="Rrule">11</td><td styleCode="Rrule">11</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Renal and Urinary Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Proteinuria<footnoteRef IDREF="t5f4"/></td><td styleCode="Rrule">16</td><td styleCode="Rrule">0</td><td styleCode="Rrule">3</td><td styleCode="Rrule">1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Nervous System Disorders</content></td></tr><tr><td styleCode="Lrule Rrule"> Peripheral neuropathy</td><td styleCode="Rrule">13</td><td styleCode="Rrule">3</td><td styleCode="Rrule">6</td><td styleCode="Rrule">0</td></tr></tbody></table>

<table width="90%"><caption>Table 6: Comparison of Adverse Events by Treatment Cycle in the Unituxin/RA Group in Study 1</caption><col width="36%" align="left" valign="bottom"/><col width="16%" align="center" valign="bottom"/><col width="16%" align="center" valign="bottom"/><col width="16%" align="center" valign="bottom"/><col width="16%" align="center" valign="bottom"/><thead><tr><th styleCode="Lrule Rrule" rowspan="2" align="center" valign="middle">Preferred Term<footnote>Includes preferred terms with a per-patient incidence of at least 20% in the Unituxin and RA group for either IL-2 or GM-CSF containing cycles.</footnote>^,<footnote>Adverse drug reactions were graded using CTCAE version 3.0.</footnote></th><th styleCode="Botrule Rrule" colspan="2" valign="middle">All Grades</th><th styleCode="Botrule Rrule" colspan="2" valign="middle">Severe</th></tr><tr><th styleCode="Rrule" align="center" valign="bottom">GM-CSF N=134 (%)</th><th styleCode="Rrule" valign="bottom">IL-2<footnote ID="t6f3">Seven patients who received GM-CSF in Cycle 1 discontinued prior to starting Cycle 2.</footnote> N=127 (%)</th><th styleCode="Rrule" valign="bottom">GM-CSF N=134 (%)</th><th styleCode="Rrule" valign="bottom">IL-2<footnoteRef IDREF="t6f3"/> N=127 (%)</th></tr></thead><tfoot><tr><td align="left" colspan="5">GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-2, interleukin-2; RA, 13-cis-retinoic acid</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">General Disorders and administration site conditions</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pyrexia</td><td styleCode="Rrule">55</td><td styleCode="Rrule">65</td><td styleCode="Rrule">10</td><td styleCode="Rrule">37</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pain<footnote>Includes preferred terms abdominal pain, abdominal pain upper, arthralgia, back pain, bladder pain, bone pain, chest pain, facial pain, gingival pain, infusion related reaction, musculoskeletal chest pain, myalgia, neck pain, neuralgia, oropharyngeal pain, pain, pain in extremity, and proctalgia.</footnote></td><td styleCode="Rrule">77</td><td styleCode="Rrule">61</td><td styleCode="Rrule">43</td><td styleCode="Rrule">35</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Blood and Lymphatic System Disorders<footnote ID="t6f5">Based on investigator-reported adverse reactions.</footnote></content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Thrombocytopenia</td><td styleCode="Rrule">62</td><td styleCode="Rrule">61</td><td styleCode="Rrule">31</td><td styleCode="Rrule">33</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Lymphopenia</td><td styleCode="Rrule">54</td><td styleCode="Rrule">61</td><td styleCode="Rrule">33</td><td styleCode="Rrule">50</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Anemia</td><td styleCode="Rrule">42</td><td styleCode="Rrule">42</td><td styleCode="Rrule">21</td><td styleCode="Rrule">24</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Neutropenia</td><td styleCode="Rrule">25</td><td styleCode="Rrule">32</td><td styleCode="Rrule">19</td><td styleCode="Rrule">28</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Immune System Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Infusion reactions</td><td styleCode="Rrule">47</td><td styleCode="Rrule">54</td><td styleCode="Rrule">10</td><td styleCode="Rrule">20</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Vascular Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypotension</td><td styleCode="Rrule">43</td><td styleCode="Rrule">54</td><td styleCode="Rrule">5</td><td styleCode="Rrule">16</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Capillary leak syndrome</td><td styleCode="Rrule">22</td><td styleCode="Rrule">36</td><td styleCode="Rrule">11</td><td styleCode="Rrule">20</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Metabolism and Nutrition Disorders</content><footnoteRef IDREF="t6f5"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyponatremia</td><td styleCode="Rrule">36</td><td styleCode="Rrule">55</td><td styleCode="Rrule">5</td><td styleCode="Rrule">21</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypokalemia</td><td styleCode="Rrule">26</td><td styleCode="Rrule">39</td><td styleCode="Rrule">13</td><td styleCode="Rrule">33</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypoalbuminemia</td><td styleCode="Rrule">29</td><td styleCode="Rrule">29</td><td styleCode="Rrule">3</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypocalcemia</td><td styleCode="Rrule">20</td><td styleCode="Rrule">21</td><td styleCode="Rrule">2</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Investigations</content><footnoteRef IDREF="t6f5"/></td></tr><tr styleCode="Botrule"><td valign="middle" styleCode="Lrule Rrule"> Increased alanine aminotransferase</td><td valign="middle" styleCode="Rrule">43</td><td valign="middle" styleCode="Rrule">48</td><td valign="middle" styleCode="Rrule">15</td><td valign="middle" styleCode="Rrule">13</td></tr><tr styleCode="Botrule"><td valign="middle" styleCode="Lrule Rrule"> Aspartate aminotransferase increased</td><td valign="middle" styleCode="Rrule">16</td><td valign="middle" styleCode="Rrule">21</td><td valign="middle" styleCode="Rrule">4</td><td valign="middle" styleCode="Rrule">7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Gastrointestinal Disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Diarrhea</td><td styleCode="Rrule">31</td><td styleCode="Rrule">37</td><td styleCode="Rrule">6</td><td styleCode="Rrule">13</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">33</td><td styleCode="Rrule">35</td><td styleCode="Rrule">3</td><td styleCode="Rrule">2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content></td></tr><tr><td styleCode="Lrule Rrule"> Urticaria</td><td styleCode="Rrule">25</td><td styleCode="Rrule">29</td><td styleCode="Rrule">7</td><td styleCode="Rrule">7</td></tr></tbody></table>

<table width="80%"><caption>Table 7: Per-patient Incidence of Selected (&#x2265;5% Grade 3 to 4) Laboratory Abnormalities in Study 3</caption><col width="50%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule" align="center" valign="middle" rowspan="2">Laboratory Test<footnote>Laboratory abnormalities with a per-patient incidence of at least 20% (all grades) and at least a 5% per-patient incidence of severe (Grade 3 or 4) laboratory abnormalities.</footnote></th><th styleCode="Botrule Rrule" colspan="2">Grade<footnote>Based on CTCAE version 4.0.</footnote></th></tr><tr><th styleCode="Rrule" align="center">All Grades %</th><th styleCode="Rrule">Grades 3 to 4 %</th></tr></thead><tfoot><tr><td align="left" colspan="3">ND, not determined</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Hematology</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Anemia</td><td styleCode="Rrule">100</td><td styleCode="Rrule">46</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Neutropenia</td><td styleCode="Rrule">99</td><td styleCode="Rrule">63</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Thrombocytopenia</td><td styleCode="Rrule">98</td><td styleCode="Rrule">49</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Chemistry</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypoalbuminemia</td><td styleCode="Rrule">100</td><td styleCode="Rrule">8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypocalcemia</td><td styleCode="Rrule">97</td><td styleCode="Rrule">7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyponatremia</td><td styleCode="Rrule">93</td><td styleCode="Rrule">36</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hyperglycemia</td><td styleCode="Rrule">87</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Aspartate Aminotransferase Increased</td><td styleCode="Rrule">84</td><td styleCode="Rrule">8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Alanine Aminotransferase Increased</td><td styleCode="Rrule">83</td><td styleCode="Rrule">13</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypokalemia</td><td styleCode="Rrule">82</td><td styleCode="Rrule">41</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypophosphatemia</td><td styleCode="Rrule">78</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Urinalysis</content><footnote>Urinalysis results were reported as positive or negative without assessment of grade.</footnote></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Urine protein</td><td styleCode="Rrule">66</td><td styleCode="Rrule">ND</td></tr><tr><td styleCode="Lrule Rrule"> Red blood cell casts</td><td styleCode="Rrule">38</td><td styleCode="Rrule">ND</td></tr></tbody></table>