6 ADVERSE REACTIONS Most common adverse reactions (incidence > 10%) are constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Emmaus Medical, Inc. at 1-877-420-6493 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 data described below reflect exposure to Endari in 187 patients, including 136 exposed for 6 months and 109 exposed for ≥1 year. Endari was studied in 2 placebo-controlled clinical trials (a phase 3 study, n=230 and a phase 2 study, n=70). In these trials, patients with sickle cell anemia or sickle β 0 -thalassemia were randomized to receive Endari (n=187) or placebo (n=111) orally twice daily for 48 weeks followed by 3 weeks of tapering. Both studies included pediatric and adult patients (5-58 years of age) and 54% were female. The majority of patients were black (97.3%), had a diagnosis of sickle cell anemia (89.9%) and were receiving hydroxyurea at baseline (63.4%). Treatment discontinuation due to adverse reactions was reported in 2.7% (n=5) of patients receiving Endari. These adverse reactions included one case each of hypersplenism, abdominal pain, dyspepsia, burning sensation, and hot flash. Serious adverse reactions were reported in both treatment groups, more frequently in the placebo group, and were consistent with the underlying disease. Three deaths (3/187=1.6%) occurred during the study in the Endari treatment group as compared to none in the placebo treatment group. None of the deaths were considered to be related to Endari treatment. Adverse reactions occurring in greater than 10% of patients treated with Endari are shown in Table 2 below. Table 2. Adverse Reactions Occurring at an Incidence > 10% in Clinical Studies of Endari Adverse reaction Endari N = 187 (%) Placebo N = 111 (%) Constipation 21 18 Nausea 19 14 Headache 18 15 Abdominal Pain Abdominal pain = abdominal pain and abdominal pain, upper 17 16 Cough 16 14 Pain in extremity 13 7 Back pain 12 5 Chest pain 12 8
adverse reactions table
<table width="80%" ID="table2"><caption>Table 2. Adverse Reactions Occurring at an Incidence > 10% in Clinical Studies of Endari</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 valign="bottom">Adverse reaction</th><th>Endari N = 187 (%)</th><th>Placebo N = 111 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td>Constipation</td><td>21</td><td>18</td></tr><tr styleCode="Botrule"><td>Nausea</td><td>19</td><td>14</td></tr><tr styleCode="Botrule"><td>Headache</td><td>18</td><td>15</td></tr><tr styleCode="Botrule"><td>Abdominal Pain<footnote ID="ft2_1">Abdominal pain = abdominal pain and abdominal pain, upper</footnote></td><td>17</td><td>16</td></tr><tr styleCode="Botrule"><td>Cough</td><td>16</td><td>14</td></tr><tr styleCode="Botrule"><td>Pain in extremity</td><td>13</td><td>7</td></tr><tr styleCode="Botrule"><td>Back pain</td><td>12</td><td>5</td></tr><tr><td>Chest pain</td><td>12</td><td>8</td></tr></tbody></table>