FDA label 25fc4057-7e8d-4944-816f-9fe798ab5003

BOXED WARNING Cardiovascular Risk NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS ). Ibuprofen tablets are contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ). Gastrointestinal Risk NSAIDS cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS ).

WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke , which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID , the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see WARNINGS, Gastrointestinal Effects-Risk of Ulceration, Bleeding, and Perforation ). Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS ). Hypertension NSAIDs including ibuprofen tablets, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including ibuprofen tablets, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Congestive Heart Failure and Edema Fluid retention and edema have been observed in some patients taking NSAIDs. Ibuprofen tablets should be used with caution in patients with fluid retention or heart failure . Gastrointestinal Effects-Risk of Ulceration, Bleeding, and Perforation NSAIDs, including ibuprofen tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1%of patients treated for 3-6 months, and in about 2-4%of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients treated with neither of these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered. Renal Effects Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Advanced Renal Disease No information is available from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Therefore, treatment with ibuprofen tablets is not recommended in these patients with advanced renal disease. If ibuprofen tablet therapy must be initiated, close monitoring of the patients renal function is advisable. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to ibuprofen tablets. Ibuprofen tablets should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS, Preexisting Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Skin Reactions NSAIDs, including ibuprofen tablets, can cause serious skin adverse events such as exfoliative dermatitis , Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Pregnancy In late pregnancy, as with other NSAIDs, ibuprofen tablets should be avoided because it may cause premature closure of the ductus arteriosus.

5 WARNINGS AND PRECAUTIONS PRASTERA® is not intended for use in children, nor males, nor women who are breastfeeding, pregnant, or who expect to become pregnant. § 9 . Monitoring of blood pressure, serum lipids, serum sex hormones is prudent. See Clinical Laboratory Evaluation, §§7.2.1, 7.2.4. PRASTERA® is not intended for use in nursing or pregnant women, children nor males (safety data is lacking). (§§ 4 , 9 ) PRASTERA® use may be prohibited by certain athletic anti-doping regulations. (§ 9.5 ) PRASTERA® may in certain patients elevate serum levels of 5-dehydroepiandrosterone, testosterone or estrogen above the normal range for healthy, non-afflicted women of similar age. Periodic measurement of serum hormones is prudent. (§7.2.1) Hypertension may occur with prasterone treatment. Monitor blood pressure closely. (§6.3.2)

6 ADVERSE REACTIONS The most-frequent adverse reactions observed in placebo-controlled, blinded clinical studies GL94-01, GL95-01, GL95-02 and GLB96-01 are as follows: The most common adverse event with PRASTERA® is acne. This is generally treatable with topical anti-acne medication. (§ 6.1 ) Another common adverse reaction is hirsutism. Both acne and hirsutism are reversible on cessation of prasterone. (§ 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact 1 (855) FLARE-FREE or FDA (1-800-FDA-1088 or www.fda.gov/medwatch ) or your doctor. 6.1 Increased Risk of Acne and Hirsutism Acne was the most frequently reported adverse event. Acne was reported less frequently by African American patients, in approximately 26%, compared to approximately 36% in Caucasian patients. The second most-frequent adverse event was hirsutism. In study GLB96-01 involving patients of Chinese extraction, hirsutism was not reported; this may indicate a decreased racial susceptibility to hirsutism. Acne and hirsutism were both reversible on cessation of prasterone therapy. In addition, both were more likely to be reported early in treatment; patients who had not developed these within the first 6 months of exposure are less likely to develop them later. 6.2 Reduced Risk of Myalgia and Other Flare Symptoms Placebo-treated patients had higher incidences of myalgia, joint disorder, anorexia, nasal ulcers and LE skin rash than did prasterone-treated patients. These differences may be due to the decreased risk of flare observed in prasterone-treated patients. § 14.1 . 6.3 Other Common Adverse Events No adverse events increase in frequency with longer duration of treatment. The Table displays all adverse events reported in a frequency of 10% or greater from either the 200 mg dose group or the placebo group for the pooled double-blind phases of Studies GL94-01 and GL95-02. Because the number of patients who received prasterone 100 mg was substantially fewer, adverse events for this group are only presented for those adverse events which were reported in ≥ 10% of either placebo or prasterone 200 mg patients. ADVERSE EVENTS WITH FREQUENCY ≥10%* (pooled GL94-01 and GL95-02 results) *Frequency > 10% in either prasterone 200 mg or placebo patients. ** P< 0.05, Placebo vs. prasterone 200 mg. COSTART TERM Placebo N=256 200mg N=253 Rash 77 (30.1%) 93 (36.8%) Acne 39 (15.2%) 91 (36.0%) ** Arthralgia 95 (37.1%) 88 (34.8%) Asthenia 70 (27.3%) 68 (26.9%) Headache 76 (29.7%) 60 (23.7%) Arthritis 58 (22.7%) 57 (22.5%) Myalgia 79 (30.9%) 55 (21.7%) ** Pain Abdomen 34 (13.3%) 41 (16.2%) Flu Syndrome 46 (18.0%) 40 (15.8%) Stomatitis Ulcer 50 (19.5%) 38 (15.0%) Hirsutism 6 (2.3%) 36 (14.2%) ** Fever 39 (15.2%) 36 (14.2%) Depression 33 (12.9%) 35 (13.8%) Alopecia 48 (18.8%) 35 (13.8%) Infection 37 (14.5%) 26 (10.3%) Sinusitis 33 (12.9%) 22 (8.7%) Pain Chest 27 (10.5%) 22 (8.7%) For adverse events occurring in < 10% of patients, the following showed an absolute difference of at least 3% between placebo or prasterone 200 mg, or, if less than 3% difference, the difference was significant (p < 0.05): ADVERSE EVENTS WITH FREQUENCY <10% AND AT LEAST A 3% OR A SIGNIFICANT DIFFERENCE (pooled GL94-01 and GL95-02 results) ** P< 0.05, Placebo vs. prasterone 200 mg. COSTART TERM Placebo N=256 prasterone 200 mg N=253 Less Frequent in Prasterone Anorexia 10 (3.9%) 2 (0.8%) ** Nasal Septum Disorder (nasal ulcers) 14 (5.5%) 5 (2.0%) ** Rash Lupus Erythematosus 13 (5.1%) 4 (1.6%) ** Joint Disorder 14 (5.5%) 4 (1.6%) ** More Frequent in Prasterone Creatinine Increase 0 (0.0%) 6 (2.4%)** Hypertension 7 (2.7%) 20 (7.9%) ** Hematuria 1 (0.4%) 9 (3.6%) ** Insignificant Difference Back Pain 16 (6.3%) 24 (9.5%) Pharyngitis 14 (5.5%) 6 (2.4%) Dyspnea 22 (8.6%) 11 (4.3%) Lymphadenopathy 21 (8.2%) 12 (4.7%) The pattern of adverse events in clinical study GLB96-01 showed a similar, but not identical pattern. Acne was the most common adverse event; this may reflect the fact that almost all patients were also receiving corticosteroids. This may also reflect racial differences in sensitivity to prasterone. By contrast, hirsutism was not reported at all in GLB96-01. ADVERSE EVENTS REPORTED BY AT LEAST 10% OF EITHER TREATMENT GROUP (GBL96-01) *P-value<0.05, Treatment vs. Placebo, chi-square test Placebo N= 59 Treatment N= 61 Arthralgia 37 ( 62.7%) 39 ( 63.9%) Acne * 17 ( 28.8%) 36 ( 59.0%)* Pharyngitis 32 ( 54.2%) 34 ( 55.7%) Myalgia 24 ( 40.7%) 28 ( 45.9%) Headache * 37 ( 62.7%) 26 ( 42.6%)* Pain Abdomen 25 ( 42.4%) 23 ( 37.7%) Asthenia 19 ( 32.2%) 18 ( 29.5%) Cough Increase 18 ( 30.5%) 18 ( 29.5%) Dizziness 19 ( 32.2%) 15 ( 24.6%) Pain Chest 11 ( 18.6%) 14 ( 23.0%) Dyspnea 8 ( 13.6%) 14 ( 23.0%) Rash 16 (27.1%) 14 ( 23.0%) Fever 17 ( 28.8%) 13 ( 21.3%) Alopecia 8 ( 13.6%) 13 ( 21.3%) Pain 8 ( 13.6%) 11 ( 18.0%) Diarrhea 11 ( 18.6%) 11 ( 18.0%) Rhinitis 13 ( 22.0%) 11 ( 18.0%) Stomatitis Ulcer 17 ( 28.8%) 10 ( 16.4%) Pain Back 10 ( 16.9%) 9 ( 14.8%) Edema 6 ( 10.2%) 9 ( 14.8%) Injury Accident 6 ( 10.2%) 8 ( 13.1%) Insomnia 7 ( 11.9%) 8 ( 13.1%) Pruritus 7 ( 11.9%) 8 ( 13.1%) Infection* 15 ( 25.4%) 6 ( 9.8%)* Dry Eye 10 ( 16.9%) 6 ( 9.8%) Vomit 8 ( 13.6%) 5 ( 8.2%) Peripheral Edema 8 ( 13.6%) 5 ( 8.2%) Rash Lupus Erythematosus 7 ( 11.9%) 5 ( 8.2%) Conjunctivitis 7 ( 11.9%) 5 ( 8.2%) Nausea 9 ( 15.3%) 4 ( 6.6%) Of adverse events reported by at least 10% of patients, acne was the only event significantly more frequent in the treatment group. Headache and infection were more frequent in the placebo group. Of the adverse events reported with an incidence of less than 10%, the only statistically significant difference was for seborrhea (0 placebo vs. 5 treatment patients). 6.3.1 Hypertension Hypertension was reported as an adverse event more frequently in the prasterone 200 mg group than placebo. When measures of increased (changed) blood pressure were included, there appeared to be no difference between the groups. Whether prasterone increases hypertension is thus not clear. 6.4 Reduced Risk of Death In the GL94-01, GL95-01 and GL95-02 placebo-controlled clinical studies (pooled data), the placebo group experienced 6 deaths in 77 patients, a risk of death of 7.8%. In contrast, the prasterone group (pooled treatment and cross-over) experienced 8 deaths in 495 patients, a risk of death of 1.6%. The risk of death from any cause was therefore five times higher in the placebo group. 6.5 Reduced Risk of Breast Cancer In the GL94-01, GL95-01 and GL95-02 placebo-controlled clinical studies (pooled data), incidence of breast cancer was 1 in 336 patient-years (0.29%) for placebo and 3 in 1573 patient-years (0.19%) for prasterone (pooled treatment and cross-over). Prasterone was thus associated with reducing the risk of breast cancer by one third. For patients over 44 years of age, the difference between placebo and prasterone groups was more pronounced. For women at least 45 years of age, the rate of breast cancer was 1 in 24 patient-years (4.2%) for placebo and 3 in 206 patient-years (1.5%) for prasterone treatment and cross-over patients. Prasterone was thus associated with reducing the risk of breast cancer by two thirds. 6.6 Other Serious Adverse Events Adverse events that were assessed as “severe” occurred in similar frequencies in both treatment and placebo groups, with asthenia being the most common adverse event reported as severe in both placebo and treated patients. Although the patient numbers are small, abdominal pain reported as a severe adverse event occurred in 6 treated 200 mg patients, 2 treated 100mg patients, and no placebo patients. Serious adverse events occurred in 39 200 mg, 7 100 mg, and 47 placebo patients participating in GL94-01 and GL95-02. However, only 3 serious adverse events were considered possibly related, 2 in the placebo group (one suicide and one patient with menomettrorhagia) and one in 200 mg (a patient with an acute psychosis). In the Taiwan study, serious adverse events were reported in a significantly higher proportion of patients in the placebo group than in the treatment group. In most cases, the types of serious adverse events reported were consistent with SLE flares or hospitalization for manifestations of SLE, rather than adverse effects of the study drug. SEVERE ADVERSE EVENTS OCCURRING IN AT LEAST 2 PATIENTS* (GL94-01 and GL95-02) *Frequency at least 2 patients in either prasterone 200 mg or placebo COSTART TERM Placebo N=256 prasterone 200 mg N=253 Asthenia 22 (8.6%) 22 (8.7%) Headache 11 (4.3%) 8( 3.2%) Arthralgia 6 (2.3%) 6 (2.4%) Pain Abdomen 0 (0%) 6 (2.4%) Rash 5 (2.0%) 6 (2.4%) Arthritis 2 (0.8%) 5 (2.0%) Dyspnea 1 (0.4%) 4 (1.6%) Depression 4 (1.6%) 2 (0.8%) Diabetes Mellitus 0 (0%) 2 (0.8%) Emotional Lability 0 (0%) 2 (0.8%) Infection 0 (0%) 2 (0.8%) Myalgia 5 (2.0%) 2 (0.8%) Pain 1 (0.4%) 2 (0.8%) Pain Chest 4 (1.6%) 2 (0.8%) Paresthesia 1 (0.4%) 2 (0.8%) Pleural Disorder 1 (0.4%) 2 (0.8%) Vasculitis 0 (0%) 2 (0.8%) Joint Disorder 2 (0.8%) 1 (0.4%) Peripheral Edema 2 (0.8%) 0 (0%) Sepsis 2 (0.8%) 0 (0%) Cyst 2 (0.8%) 0 (0%) Thinking Abnormal 2 (0.8%) 0 (0%)

ADVERSE REACTIONS The most frequent type of adverse reaction occurring with ibuprofen tablets is gastrointestinal . In controlled clinical trials the percentage of patients reporting one or more gastrointestinal complaints ranged from 4%to 16%. In controlled studies when ibuprofen tablets were compared to aspirin and indomethacin in equally effective doses, the overall incidence of gastrointestinal complaints was about half that seen in either the aspirin- or indomethacin-treated patients. Adverse reactions observed during controlled clinical trials at an incidence greater than 1%are listed in the table. Those reactions listed in Column one encompass observations in approximately 3,000 patients. More than 500 of these patients were treated for periods of at least 54 weeks. Still other reactions occurring less frequently than 1 in 100 were reported in controlled clinical trials and from marketing experience. These reactions have been divided into two categories: Column two of the table lists reactions with therapy with ibuprofen tablets where the probability of a causal relationship exists: for the reactions in Column three, a causal relationship with ibuprofen tablets has not been established. Reported side effects were higher at doses of 3200 mg/day than at doses of 2400 mg or less per day in clinical trials of patients with rheumatoid arthritis . The increases in incidence were slight and still within the ranges reported in the table. * Reactions are classified under "Probable Causal Relationship (PCR)" if there has been one positive rechallenge or if three or more cases occur which might be causally related. Reactions are classified under "Causal Relationship Unknown" if seven or more events have been reported but the criteria for PCR have not been met. † Reactions occurring in 3% to 9% of patients treated with ibuprofen tablets. (Those reactions occurring in less than 3% of the patients are unmarked). Incidence Greater than 1% (but less than 3%) probable casual Relationship Precise Incidence Unknown (but less than 1%) probable Casual Relationship* Precise Incidence Unknown (but less than 1%) Casual Relationship Unknown* GASTROINTESTINAL Nausea†, epigastric paint†, heartburn, diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or Pain, fullness of GI tract (bloating and flatulence) Gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests; pancreatis CENTRAL NERVOUS SYSTEM Dizziness†, headache, nervousness Depression, insomnia, confusion, emotional liability, somnolence, aseptic meningitis with fever and coma (see PRECAUTIONS ) Paresthesias, hallucinations, dream abnormalities, pseudo-tumor cerebri DERMATOLOGIC Rash† (including maculopapular type), pruritis Vesiculobullous eruptions, urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia Toxic epidermal necrolysis, photoallergic skin reactions SPECIAL SENSES Tinnitus Hearing loss, amblyopia (blurred and/or diminished vision, scotomata and/or changes in color vision) (see PRECAUTIONS ) Conjuctivitis, diplopia, optic neuritis, cataracts HEMATOLOGIC Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes Coombs positive), thrombocytopenia with or without purpura, eosinophilia, decreases in hemoglobin and hematocrit (see PRECAUTIONS ) Bleeding episodes (eg epistaxis, menorrhagia) METABOLIC/ENDOCRINE Decreased appetite Gynecomastia, hypoglycemic reaction, acidosis CARDIOVASCULAR Edema, fluid retention (generally responds promptly to drug discontinuation) (see PRECAUTIONS ) Congestive heart failure in patients with marginal cardiac function elevated blood pressure, palpitations Arrhythmias (sinus tachycardia, sinus bradycardia) ALLERGIC Syndrome of abdominal pain, fever, chills, nausea and vomiting; anaphylaxis; bronchospasm (see CONTRADICATIONS ) Serum sickness, lupuserythematosus syndrome, Henoch-Schonlein vasculitis, angioedema RENAL Acute renal failure see PRECAUTIONS ), decreased creatinine clearance, polyuria, azotemia, cystitis, Hematuria Renal papillary necrosis MISCELLANEOUS Dry eyes and mouth, gingival ulcer, rhinitis

<table ID="t300" width="100%"> <caption>ADVERSE EVENTS WITH FREQUENCY &#x2265;10%* (pooled GL94-01 and GL95-02 results) </caption> <col width="35.267%" align="left"/> <col width="31.633%" align="left"/> <col width="33.100%" align="left"/> <tfoot> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote">*Frequency &gt; 10% in either prasterone 200 mg or placebo patients. </paragraph> </td> </tr> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote">** P&lt; 0.05, Placebo vs. prasterone 200 mg. </paragraph> </td> </tr> </tfoot> <tbody> <tr> <td align="center" valign="bottom" styleCode="Toprule Botrule Lrule Rrule">COSTART TERM </td> <td align="center" valign="bottom" styleCode="Toprule Botrule Rrule">Placebo N=256 </td> <td align="center" valign="bottom" styleCode="Toprule Botrule Rrule">200mg N=253 </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Rash </td> <td align="center" valign="top" styleCode="Botrule Rrule">77 (30.1%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">93 (36.8%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Acne </td> <td align="center" valign="top" styleCode="Botrule Rrule">39 (15.2%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">91 (36.0%) ** </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Arthralgia </td> <td align="center" valign="top" styleCode="Botrule Rrule">95 (37.1%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">88 (34.8%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Asthenia </td> <td align="center" valign="top" styleCode="Botrule Rrule">70 (27.3%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">68 (26.9%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Headache </td> <td align="center" valign="top" styleCode="Botrule Rrule">76 (29.7%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">60 (23.7%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Arthritis </td> <td align="center" valign="top" styleCode="Botrule Rrule">58 (22.7%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">57 (22.5%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Myalgia </td> <td align="center" valign="top" styleCode="Botrule Rrule">79 (30.9%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">55 (21.7%) ** </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Pain Abdomen </td> <td align="center" valign="top" styleCode="Botrule Rrule">34 (13.3%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">41 (16.2%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Flu Syndrome </td> <td align="center" valign="top" styleCode="Botrule Rrule">46 (18.0%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">40 (15.8%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Stomatitis Ulcer </td> <td align="center" valign="top" styleCode="Botrule Rrule">50 (19.5%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">38 (15.0%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Hirsutism </td> <td align="center" valign="top" styleCode="Botrule Rrule">6 (2.3%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">36 (14.2%) ** </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Fever </td> <td align="center" valign="top" styleCode="Botrule Rrule">39 (15.2%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">36 (14.2%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Depression </td> <td align="center" valign="top" styleCode="Botrule Rrule">33 (12.9%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">35 (13.8%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Alopecia </td> <td align="center" valign="top" styleCode="Botrule Rrule">48 (18.8%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">35 (13.8%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Infection </td> <td align="center" valign="top" styleCode="Botrule Rrule">37 (14.5%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">26 (10.3%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Sinusitis </td> <td align="center" valign="top" styleCode="Botrule Rrule">33 (12.9%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">22 (8.7%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Pain Chest </td> <td align="center" valign="top" styleCode="Botrule Rrule">27 (10.5%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">22 (8.7%) </td> </tr> </tbody> </table>

<table ID="t301" width="100%"> <caption>ADVERSE EVENTS WITH FREQUENCY &lt;10% AND AT LEAST A 3% OR A SIGNIFICANT DIFFERENCE (pooled GL94-01 and GL95-02 results) </caption> <col width="45.033%" align="left"/> <col width="25.067%" align="left"/> <col width="29.900%" align="left"/> <tfoot> <tr> <td colspan="3" align="left" valign="top"> <paragraph styleCode="footnote">** P&lt; 0.05, Placebo vs. prasterone 200 mg. </paragraph> </td> </tr> </tfoot> <tbody> <tr> <td align="center" valign="bottom" styleCode="Toprule Botrule Lrule Rrule">COSTART TERM </td> <td align="center" valign="bottom" styleCode="Toprule Botrule Rrule">Placebo N=256 </td> <td align="center" valign="bottom" styleCode="Toprule Botrule Rrule">prasterone 200 mg N=253 </td> </tr> <tr> <td align="center" valign="top" styleCode="Botrule Lrule Rrule">Less Frequent in Prasterone </td> <td align="center" valign="top" styleCode="Botrule Rrule"/> <td align="center" valign="top" styleCode="Botrule Rrule"/> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Anorexia </td> <td align="center" valign="top" styleCode="Botrule Rrule">10 (3.9%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">2 (0.8%) ** </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Nasal Septum Disorder (nasal ulcers) </td> <td align="center" valign="top" styleCode="Botrule Rrule">14 (5.5%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">5 (2.0%) ** </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Rash Lupus Erythematosus </td> <td align="center" valign="top" styleCode="Botrule Rrule">13 (5.1%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">4 (1.6%) ** </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Joint Disorder </td> <td align="center" valign="top" styleCode="Botrule Rrule">14 (5.5%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">4 (1.6%) ** </td> </tr> <tr> <td align="center" valign="top" styleCode="Botrule Lrule Rrule">More Frequent in Prasterone </td> <td align="center" valign="top" styleCode="Botrule Rrule"/> <td align="center" valign="top" styleCode="Botrule Rrule"/> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Creatinine Increase </td> <td align="center" valign="top" styleCode="Botrule Rrule">0 (0.0%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">6 (2.4%)** </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Hypertension </td> <td align="center" valign="top" styleCode="Botrule Rrule">7 (2.7%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">20 (7.9%) ** </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Hematuria </td> <td align="center" valign="top" styleCode="Botrule Rrule">1 (0.4%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">9 (3.6%) ** </td> </tr> <tr> <td align="center" valign="top" styleCode="Botrule Lrule Rrule">Insignificant Difference </td> <td align="center" valign="top" styleCode="Botrule Rrule"/> <td align="center" valign="top" styleCode="Botrule Rrule"/> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Back Pain </td> <td align="center" valign="top" styleCode="Botrule Rrule">16 (6.3%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">24 (9.5%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Pharyngitis </td> <td align="center" valign="top" styleCode="Botrule Rrule">14 (5.5%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">6 (2.4%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Dyspnea </td> <td align="center" valign="top" styleCode="Botrule Rrule">22 (8.6%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">11 (4.3%) </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Lymphadenopathy </td> <td align="center" valign="top" styleCode="Botrule Rrule">21 (8.2%) </td> <td align="center" valign="top" styleCode="Botrule Rrule">12 (4.7%) </td> </tr> </tbody> </table>