FDA label 39aca241-342d-3d5f-e063-6394a90a7cdf

5. WARNINGS AND PRECAUTIONS Ocular Toxicity TRUSELTIQ can cause retinal pigment epithelial detachment (RPED). Perform comprehensive ophthalmic examination including optical coherence tomography (OCT) prior to initiation of TRUSELTIQ and at 1 month, at 3 months, and then every 3 months thereafter during treatment. Withhold as recommended. ( 2.3 , 5.1 ) Hyperphosphatemia and Soft Tissue Mineralization: Increases in phosphate levels can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification. Withhold, dose reduce, or permanently discontinue as recommended. ( 2.3 , 5.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Ocular Toxicity Retinal Pigment Epithelial Detachment (RPED) TRUSELTIQ can cause RPED, which may cause symptoms such as blurred vision. Among 351 patients who received TRUSELTIQ across clinical trials [ see Adverse Reactions ( 6.1 ) ] where ophthalmologic monitoring did not routinely include optical coherence tomography (OCT), RPED occurred in 11% of patients, including patients with asymptomatic RPED. The median time to first onset of RPED was 26 days. RPED led to dose interruption/reduction of TRUSELTIQ in 3.4% of patients, and permanent discontinuation in 0.6% of patients. Perform a comprehensive ophthalmic examination including OCT prior to initiation of TRUSELTIQ, at 1 month, at 3 months, and then every 3 months thereafter during treatment. Refer patients for ophthalmic evaluation urgently for onset of visual symptoms, and follow-up every 3 weeks until resolution or discontinuation of TRUSELTIQ. Withhold TRUSELTIQ as recommended [ see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.1 ) ]. Dry Eye Among 351 patients who received TRUSELTIQ across clinical trials [ see Adverse Reactions ( 6.1 ) ], dry eye occurred in 29% of patients. Treat patients with ocular demulcents as needed. 5.2 Hyperphosphatemia and Soft Tissue Mineralization TRUSELTIQ can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification. Increases in phosphate levels are a pharmacodynamic effect of TRUSELTIQ [ see Clinical Pharmacology ( 12.2 ) ]. Among 351 patients who received TRUSELTIQ across clinical trials [ see Adverse Reactions ( 6.1 ) ], hyperphosphatemia was reported in 82% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-349). Phosphate binders were received by 83% of patients who received TRUSELTIQ. Monitor for hyperphosphatemia throughout treatment. Initiate phosphate lowering therapy when serum phosphate level is >5.5 mg/dL. For serum phosphate level >7.5 mg/dL, withhold TRUSELTIQ and initiate phosphate lowering therapy. Withhold, dose reduce, or permanently discontinue TRUSELTIQ based on duration and severity of hyperphosphatemia [ see Dosage and Administration ( 2.3 ) ]. 5.3 Embryo-Fetal Toxicity Based on findings in animal studies and its mechanism of action, TRUSELTIQ can cause fetal harm when administered to a pregnant woman. Oral administration of infigratinib to pregnant animals during the period of organogenesis caused malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 125 mg. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose [ see Use in Specific Populations ( 8.1 , 8.3 ) ].

5.1 Ocular Toxicity Retinal Pigment Epithelial Detachment (RPED) TRUSELTIQ can cause RPED, which may cause symptoms such as blurred vision. Among 351 patients who received TRUSELTIQ across clinical trials [ see Adverse Reactions ( 6.1 ) ] where ophthalmologic monitoring did not routinely include optical coherence tomography (OCT), RPED occurred in 11% of patients, including patients with asymptomatic RPED. The median time to first onset of RPED was 26 days. RPED led to dose interruption/reduction of TRUSELTIQ in 3.4% of patients, and permanent discontinuation in 0.6% of patients. Perform a comprehensive ophthalmic examination including OCT prior to initiation of TRUSELTIQ, at 1 month, at 3 months, and then every 3 months thereafter during treatment. Refer patients for ophthalmic evaluation urgently for onset of visual symptoms, and follow-up every 3 weeks until resolution or discontinuation of TRUSELTIQ. Withhold TRUSELTIQ as recommended [ see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.1 ) ]. Dry Eye Among 351 patients who received TRUSELTIQ across clinical trials [ see Adverse Reactions ( 6.1 ) ], dry eye occurred in 29% of patients. Treat patients with ocular demulcents as needed.

5.2 Hyperphosphatemia and Soft Tissue Mineralization TRUSELTIQ can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification. Increases in phosphate levels are a pharmacodynamic effect of TRUSELTIQ [ see Clinical Pharmacology ( 12.2 ) ]. Among 351 patients who received TRUSELTIQ across clinical trials [ see Adverse Reactions ( 6.1 ) ], hyperphosphatemia was reported in 82% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-349). Phosphate binders were received by 83% of patients who received TRUSELTIQ. Monitor for hyperphosphatemia throughout treatment. Initiate phosphate lowering therapy when serum phosphate level is >5.5 mg/dL. For serum phosphate level >7.5 mg/dL, withhold TRUSELTIQ and initiate phosphate lowering therapy. Withhold, dose reduce, or permanently discontinue TRUSELTIQ based on duration and severity of hyperphosphatemia [ see Dosage and Administration ( 2.3 ) ].

5.3 Embryo-Fetal Toxicity Based on findings in animal studies and its mechanism of action, TRUSELTIQ can cause fetal harm when administered to a pregnant woman. Oral administration of infigratinib to pregnant animals during the period of organogenesis caused malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 125 mg. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose [ see Use in Specific Populations ( 8.1 , 8.3 ) ].

6. ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: Ocular Toxicity [ see Warnings and Precautions ( 5.1 ) ] Hyperphosphatemia and Soft Tissue Mineralization [ see Warnings and Precautions ( 5.2 ) ] Most common (≥20%) adverse reactions were nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, vision blurred and vomiting. ( 6.1 ) Most common laboratory abnormalities (≥20%) were increased creatinine, increased phosphate, decreased phosphate, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased lipase, increased calcium, decreased lymphocytes, decreased sodium, increased triglycerides, increased aspartate aminotransferase, increased urate, decreased platelets, decreased leukocytes, decreased albumin, increased bilirubin and decreased potassium. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact QED Therapeutics, Inc. at 1-844-550-BBIO (2246) 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 the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to TRUSELTIQ as a single agent at 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles in 351 patients in Study CBGJ398X2204 and in patients with other advanced solid tumors or hematological malignancies. Among 351 patients who received TRUSELTIQ, 27% were exposed for 6 months or longer and 10% were exposed for greater than one year. Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma The safety of TRUSELTIQ was evaluated in Study CBGJ398X2204, which included 108 patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement [ see Clinical Studies ( 14.1 ) ]. Patients were treated orally with TRUSELTIQ 125 mg once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles, until disease progression or unacceptable toxicity. The median duration of treatment was 5.5 months (range: 0.03 to 28.3 months). The median age of TRUSELTIQ treated patients was 53 years (range 23-81), 62% were females, and 72% were White. Serious adverse reactions occurred in 32% of patients receiving TRUSELTIQ. Serious adverse reactions in ≥2% of patients who received TRUSELTIQ included infections, anemia, pyrexia, abdominal pain, hypercalcemia, and sepsis. Fatal adverse reactions occurred in 1 (0.9%) patient who received TRUSELTIQ and was due to sepsis. Permanent discontinuation due to an adverse reaction occurred in 15% of patients who received TRUSELTIQ. Adverse reactions requiring permanent discontinuation in ≥1% of patients were blood creatinine increased, fatigue, subretinal fluid, and calcinosis. Dosage interruptions due to an adverse reaction occurred in 64% of patients who received TRUSELTIQ. Adverse reactions requiring dosage interruption in ≥5% of patients included hyperphosphatemia, hypercalcemia, palmar-plantar erythrodysesthesia syndrome, stomatitis, diarrhea, and blood creatinine increased. Dosage reductions due to an adverse reaction occurred in 60% of patients who received TRUSELTIQ. Adverse reactions requiring dosage reductions in ≥2% of patients who received TRUSELTIQ included hyperphosphatemia, stomatitis, palmar-plantar erythrodysesthesia syndrome, increased blood creatinine, increased lipase, hypercalcemia, and onycholysis. The most common (≥20%) adverse reactions were nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, vision blurred and vomiting. The most common laboratory abnormalities (≥20%) were increased creatinine, increased phosphate, decreased phosphate, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased lipase, increased calcium, decreased lymphocytes, decreased sodium, increased triglycerides, increased aspartate aminotransferase, increased urate, decreased platelets, decreased leukocytes, decreased albumin, increased bilirubin and decreased potassium. Table 3 summarizes the adverse reactions in Study CBGJ398X2204. Table 4 summarizes select laboratory abnormalities in Study CBGJ398X2204. Table 3: Adverse Reactions (≥15%) in Patients Receiving TRUSELTIQ in Study CBGJ398X2204 TRUSELTIQ N=108 Adverse Reaction All Grades (%) Grades 3 or 4 a (%) Skin and subcutaneous tissue disorders Nail toxicity b 57 2* Alopecia 38 0 Palmar-plantar erythrodysesthesia syndrome 33 7* Dry skin 23 0 Gastrointestinal disorders Stomatitis c 56 15* Constipation 30 1* Abdominal pain d 26 5* Dry mouth 25 0 Diarrhea 24 3* Vomiting 21 1* Nausea 19 1* Dyspepsia 17 0 Eye disorders e Dry eye f 44 0 Eyelash changes g 25 0 Vision blurred 21 0 General disorders and administrative site conditions Fatigue h 44 4* Edema i 17 1* Pyrexia 15 1* Musculoskeletal and connective tissue disorders Arthralgia 32 0 Pain in extremity 17 2* Nervous system disorders Dysgeusia 32 0 Headache 17 1* Metabolism and nutrition disorders Decreased appetite 22 1* Respiratory, thoracic and mediastinal disorders Epistaxis 18 0 Investigations Weight decreased 15 2* Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.03). a Events of Grade 3 only (no Grade 4 occurred) are marked with an asterisk. b Includes ingrown nail, nail bed bleeding, nail bed disorder, nail bed inflammation, nail bed tenderness, nail discoloration, nail disorder, nail dystrophy, nail hypertrophy, nail infection, nail ridging, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomycosis, and paronychia. c Includes mouth ulceration and stomatitis. d Includes abdominal pain, abdominal pain upper, abdominal discomfort, and abdominal pain lower. e Severity of eye disorders is not represented by CTCAE Grading f Includes dry eye, keratitis, lacrimation increased, pinguecula, and punctate keratitis. g Includes blepharitis, eyelash changes, eyelash discoloration, growth of eyelashes, trichiasis, and trichomegaly. h Includes asthenia and fatigue. i Includes edema peripheral and edema. Clinically relevant adverse reactions occurring in ≤15% of patients included cataracts (12%) and fractures (1%). Table 4: Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients Receiving TRUSELTIQ in Study CBGJ398X2204 TRUSELTIQ N=108 Laboratory Abnormality All Grades (%) Grade 3 or 4 (%) Hematology Decreased hemoglobin 53 5 Decreased lymphocytes 43 9 Decreased platelets 37 4 Decreased leukocytes 26 3 Decreased neutrophils 14 2 Chemistry Increased creatinine 93 7 Increased phosphate a 90 13 Decreased phosphate 64 31 Increased alkaline phosphatase 54 8 Increased alanine aminotransferase 51 6 Increased lipase 44 7 Increased calcium 43 7 Decreased sodium 41 20 Increased triglycerides 38 3 Increased aspartate aminotransferase 38 4 Increased urate 37 37 Decreased albumin 24 1 Increased bilirubin 24 6 Decreased potassium 21 3 Increased cholesterol 18 1 Increased potassium 17 3 Decreased calcium 10 2 The denominator used to calculate the rate varied from 104 to 107 based on the number of patients with a baseline value and at least one post-treatment value. These laboratory abnormalities are values that reflect worsening from baseline. Graded per NCI CTCAE 4.03. a NCI CTCAE 4.03 does not define grades for increased phosphate. Laboratory value shift table categories were used to assess increased phosphorus levels (Grades ≥3 defined as ≥9mg/dL).

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 the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to TRUSELTIQ as a single agent at 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles in 351 patients in Study CBGJ398X2204 and in patients with other advanced solid tumors or hematological malignancies. Among 351 patients who received TRUSELTIQ, 27% were exposed for 6 months or longer and 10% were exposed for greater than one year. Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma The safety of TRUSELTIQ was evaluated in Study CBGJ398X2204, which included 108 patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement [ see Clinical Studies ( 14.1 ) ]. Patients were treated orally with TRUSELTIQ 125 mg once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles, until disease progression or unacceptable toxicity. The median duration of treatment was 5.5 months (range: 0.03 to 28.3 months). The median age of TRUSELTIQ treated patients was 53 years (range 23-81), 62% were females, and 72% were White. Serious adverse reactions occurred in 32% of patients receiving TRUSELTIQ. Serious adverse reactions in ≥2% of patients who received TRUSELTIQ included infections, anemia, pyrexia, abdominal pain, hypercalcemia, and sepsis. Fatal adverse reactions occurred in 1 (0.9%) patient who received TRUSELTIQ and was due to sepsis. Permanent discontinuation due to an adverse reaction occurred in 15% of patients who received TRUSELTIQ. Adverse reactions requiring permanent discontinuation in ≥1% of patients were blood creatinine increased, fatigue, subretinal fluid, and calcinosis. Dosage interruptions due to an adverse reaction occurred in 64% of patients who received TRUSELTIQ. Adverse reactions requiring dosage interruption in ≥5% of patients included hyperphosphatemia, hypercalcemia, palmar-plantar erythrodysesthesia syndrome, stomatitis, diarrhea, and blood creatinine increased. Dosage reductions due to an adverse reaction occurred in 60% of patients who received TRUSELTIQ. Adverse reactions requiring dosage reductions in ≥2% of patients who received TRUSELTIQ included hyperphosphatemia, stomatitis, palmar-plantar erythrodysesthesia syndrome, increased blood creatinine, increased lipase, hypercalcemia, and onycholysis. The most common (≥20%) adverse reactions were nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, vision blurred and vomiting. The most common laboratory abnormalities (≥20%) were increased creatinine, increased phosphate, decreased phosphate, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased lipase, increased calcium, decreased lymphocytes, decreased sodium, increased triglycerides, increased aspartate aminotransferase, increased urate, decreased platelets, decreased leukocytes, decreased albumin, increased bilirubin and decreased potassium. Table 3 summarizes the adverse reactions in Study CBGJ398X2204. Table 4 summarizes select laboratory abnormalities in Study CBGJ398X2204. Table 3: Adverse Reactions (≥15%) in Patients Receiving TRUSELTIQ in Study CBGJ398X2204 TRUSELTIQ N=108 Adverse Reaction All Grades (%) Grades 3 or 4 a (%) Skin and subcutaneous tissue disorders Nail toxicity b 57 2* Alopecia 38 0 Palmar-plantar erythrodysesthesia syndrome 33 7* Dry skin 23 0 Gastrointestinal disorders Stomatitis c 56 15* Constipation 30 1* Abdominal pain d 26 5* Dry mouth 25 0 Diarrhea 24 3* Vomiting 21 1* Nausea 19 1* Dyspepsia 17 0 Eye disorders e Dry eye f 44 0 Eyelash changes g 25 0 Vision blurred 21 0 General disorders and administrative site conditions Fatigue h 44 4* Edema i 17 1* Pyrexia 15 1* Musculoskeletal and connective tissue disorders Arthralgia 32 0 Pain in extremity 17 2* Nervous system disorders Dysgeusia 32 0 Headache 17 1* Metabolism and nutrition disorders Decreased appetite 22 1* Respiratory, thoracic and mediastinal disorders Epistaxis 18 0 Investigations Weight decreased 15 2* Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.03). a Events of Grade 3 only (no Grade 4 occurred) are marked with an asterisk. b Includes ingrown nail, nail bed bleeding, nail bed disorder, nail bed inflammation, nail bed tenderness, nail discoloration, nail disorder, nail dystrophy, nail hypertrophy, nail infection, nail ridging, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomycosis, and paronychia. c Includes mouth ulceration and stomatitis. d Includes abdominal pain, abdominal pain upper, abdominal discomfort, and abdominal pain lower. e Severity of eye disorders is not represented by CTCAE Grading f Includes dry eye, keratitis, lacrimation increased, pinguecula, and punctate keratitis. g Includes blepharitis, eyelash changes, eyelash discoloration, growth of eyelashes, trichiasis, and trichomegaly. h Includes asthenia and fatigue. i Includes edema peripheral and edema. Clinically relevant adverse reactions occurring in ≤15% of patients included cataracts (12%) and fractures (1%). Table 4: Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients Receiving TRUSELTIQ in Study CBGJ398X2204 TRUSELTIQ N=108 Laboratory Abnormality All Grades (%) Grade 3 or 4 (%) Hematology Decreased hemoglobin 53 5 Decreased lymphocytes 43 9 Decreased platelets 37 4 Decreased leukocytes 26 3 Decreased neutrophils 14 2 Chemistry Increased creatinine 93 7 Increased phosphate a 90 13 Decreased phosphate 64 31 Increased alkaline phosphatase 54 8 Increased alanine aminotransferase 51 6 Increased lipase 44 7 Increased calcium 43 7 Decreased sodium 41 20 Increased triglycerides 38 3 Increased aspartate aminotransferase 38 4 Increased urate 37 37 Decreased albumin 24 1 Increased bilirubin 24 6 Decreased potassium 21 3 Increased cholesterol 18 1 Increased potassium 17 3 Decreased calcium 10 2 The denominator used to calculate the rate varied from 104 to 107 based on the number of patients with a baseline value and at least one post-treatment value. These laboratory abnormalities are values that reflect worsening from baseline. Graded per NCI CTCAE 4.03. a NCI CTCAE 4.03 does not define grades for increased phosphate. Laboratory value shift table categories were used to assess increased phosphorus levels (Grades ≥3 defined as ≥9mg/dL).

<table border="0" ID="table-3" width="100%"><caption>Table 3: Adverse Reactions (&#x2265;15%) in Patients Receiving TRUSELTIQ in Study CBGJ398X2204</caption><tbody><tr><td/><td colspan="2" rowspan="1"><paragraph><content styleCode="bold">TRUSELTIQ</content></paragraph><content styleCode="bold">N=108</content></td></tr><tr><td><content styleCode="bold">Adverse Reaction</content></td><td><content styleCode="bold">All Grades (%) </content></td><td><content styleCode="bold">Grades 3 or 4 ^a (%) </content></td></tr><tr><td colspan="3">Skin and subcutaneous tissue disorders</td></tr><tr><td>Nail toxicity ^b</td><td>57</td><td>2*</td></tr><tr><td>Alopecia</td><td>38</td><td>0</td></tr><tr><td>Palmar-plantar erythrodysesthesia syndrome</td><td>33</td><td>7*</td></tr><tr><td><paragraph>Dry skin</paragraph></td><td>23</td><td>0</td></tr><tr><td colspan="3"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td></tr><tr><td><paragraph>Stomatitis ^c</paragraph></td><td>56</td><td>15*</td></tr><tr><td>Constipation</td><td>30</td><td>1*</td></tr><tr><td><paragraph>Abdominal pain ^d</paragraph></td><td>26</td><td>5*</td></tr><tr><td><paragraph>Dry mouth</paragraph></td><td>25</td><td>0</td></tr><tr><td>Diarrhea</td><td>24</td><td>3*</td></tr><tr><td>Vomiting</td><td>21</td><td>1*</td></tr><tr><td>Nausea</td><td>19</td><td>1*</td></tr><tr><td>Dyspepsia</td><td>17</td><td>0</td></tr><tr><td colspan="3"><paragraph><content styleCode="bold">Eye disorders ^e</content></paragraph></td></tr><tr><td><paragraph>Dry eye ^f</paragraph></td><td>44</td><td>0</td></tr><tr><td><paragraph>Eyelash changes ^g</paragraph></td><td>25</td><td>0</td></tr><tr><td><paragraph>Vision blurred</paragraph></td><td>21</td><td>0</td></tr><tr><td colspan="3"><paragraph><content styleCode="bold">General disorders and administrative site conditions</content></paragraph></td></tr><tr><td><paragraph>Fatigue ^h</paragraph></td><td>44</td><td>4*</td></tr><tr><td><paragraph>Edema ⁱ</paragraph></td><td>17</td><td>1*</td></tr><tr><td><paragraph>Pyrexia</paragraph></td><td>15</td><td>1*</td></tr><tr><td colspan="3"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td><paragraph>Arthralgia</paragraph></td><td>32</td><td>0</td></tr><tr><td><paragraph>Pain in extremity</paragraph></td><td>17</td><td>2*</td></tr><tr><td colspan="3"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td></tr><tr><td><paragraph>Dysgeusia</paragraph></td><td>32</td><td>0</td></tr><tr><td><paragraph>Headache</paragraph></td><td>17</td><td>1*</td></tr><tr><td colspan="3"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td><paragraph>Decreased appetite</paragraph></td><td>22</td><td>1*</td></tr><tr><td colspan="3"><paragraph><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td><paragraph>Epistaxis</paragraph></td><td>18</td><td>0</td></tr><tr><td colspan="3"><paragraph><content styleCode="bold">Investigations</content></paragraph></td></tr><tr><td><paragraph>Weight decreased</paragraph></td><td>15</td><td>2*</td></tr></tbody></table>

<table border="0" ID="table-4" width="100%"><caption>Table 4: Select Laboratory Abnormalities (&#x2265;10%) Worsening from Baseline in Patients Receiving TRUSELTIQ in Study CBGJ398X2204</caption><tbody><tr><td/><td colspan="2" rowspan="1"><paragraph><content styleCode="bold">TRUSELTIQ</content></paragraph><paragraph><content styleCode="bold">N=108</content></paragraph></td></tr><tr><td><content styleCode="bold">Laboratory Abnormality</content></td><td><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td><td><paragraph><content styleCode="bold">Grade 3 or 4</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td></tr><tr><td colspan="3">Hematology</td></tr><tr><td>Decreased hemoglobin</td><td>53</td><td>5</td></tr><tr><td>Decreased lymphocytes</td><td>43</td><td>9</td></tr><tr><td>Decreased platelets</td><td>37</td><td>4</td></tr><tr><td>Decreased leukocytes</td><td>26</td><td>3</td></tr><tr><td>Decreased neutrophils</td><td>14</td><td>2</td></tr><tr><td colspan="3">Chemistry</td></tr><tr><td>Increased creatinine</td><td>93</td><td>7</td></tr><tr><td>Increased phosphate ^a</td><td>90</td><td>13</td></tr><tr><td>Decreased phosphate</td><td>64</td><td>31</td></tr><tr><td>Increased alkaline phosphatase</td><td>54</td><td>8</td></tr><tr><td>Increased alanine aminotransferase</td><td>51</td><td>6</td></tr><tr><td>Increased lipase</td><td>44</td><td>7</td></tr><tr><td>Increased calcium</td><td>43</td><td>7</td></tr><tr><td>Decreased sodium</td><td>41</td><td>20</td></tr><tr><td>Increased triglycerides</td><td>38</td><td>3</td></tr><tr><td>Increased aspartate aminotransferase</td><td>38</td><td>4</td></tr><tr><td>Increased urate</td><td>37</td><td>37</td></tr><tr><td>Decreased albumin</td><td>24</td><td>1</td></tr><tr><td>Increased bilirubin</td><td>24</td><td>6</td></tr><tr><td>Decreased potassium</td><td>21</td><td>3</td></tr><tr><td>Increased cholesterol</td><td>18</td><td>1</td></tr><tr><td>Increased potassium</td><td>17</td><td>3</td></tr><tr><td>Decreased calcium</td><td>10</td><td>2</td></tr></tbody></table>