Bexarotene
Generic: BEXAROTENE
Basic Information
Manufacturer
ANI Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
e713c60d-f623-4260-b0ca-db07e1365fd2
Indications & Usage
1 INDICATIONS AND USAGE Bexarotene capsules are indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy.
Bexarotene capsules are a retinoid indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy.
( 1 )
Bexarotene capsules are a retinoid indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the prescribing information: • Hyperlipidemia [ see Warnings and Precautions (5.1) ] • Pancreatitis [ see Warnings and Precautions (5.2) ] • Hepatotoxicity, cholestasis, and hepatic failure [ see Warnings and Precautions (5.3) ] • Hypothyroidism [ see Warnings and Precautions (5.4) ] • Neutropenia [ see Warnings and Precautions (5.5) ] • Cataracts [ see Warnings and Precautions (5.6) ] • Vitamin A Supplementation Hazard [ see Warnings and Precautions (5.7) ] • Hypoglycemia Risk in Patients with Diabetes Mellitus [ see Warnings and Precautions (5.8) ] • Photosensitivity [ see Warnings and Precautions (5.9) ] • Laboratory Tests [ see Warnings and Precautions (5.10) ] • Drug/Laboratory Test Interactions [ see Warnings and Precautions (5.11) ] The most common adverse reactions (greater than 10%) include: hyperlipidemia, hypercholesteremia, headache, hypothyroidism, asthenia, leukopenia, rash, nausea, infection, peripheral edema, abdominal pain, and dry skin.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc.
at 1-855-204-1431 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 safety of bexarotene has been evaluated in two clinical trials of 152 patients with CTCL who received bexarotene capsules for up to 97 weeks and in 352 patients in other trials.
The mean duration of therapy for the 152 patients with CTCL was 166 days.
The most common adverse events reported with an incidence of at least 10% in patients with CTCL treated at an initial dose of 300 mg/m 2 /day of bexarotene capsules are shown in Table 2.
The events at least possibly related to treatment are lipid abnormalities (elevated triglycerides, elevated total and LDL cholesterol and decreased HDL cholesterol), hypothyroidism, headache, asthenia, rash, leukopenia, anemia, nausea, infection, peripheral edema, abdominal pain, and dry skin.
Most adverse events occurred at a greater incidence in patients treated at starting doses of greater than 300 mg/m 2 /day (see Table 2).
Adverse reactions leading to bexarotene capsule dose reduction or discontinuation in at least two patients were hyperlipemia, neutropenia/leukopenia, diarrhea, fatigue/lethargy, hypothyroidism, headache, liver function test abnormalities, rash, pancreatitis, nausea, anemia, allergic reaction, muscle spasm, pneumonia, and confusion.
The NCI Grade 3 and NCI Grade 4 adverse reactions reported in two or more patients with CTCL treated at an initial dose of 300 mg/m 2 /day of bexarotene capsules (see Table 3) were hypertriglyceridemia, pruritus, headache, peripheral edema, leukopenia, rash, and hypercholesteremia.
Most of these moderately severe or severe adverse events occurred at a higher rate in patients treated at starting doses of greater than 300 mg/m 2 /day than in patients treated at a starting dose of 300 mg/m 2 /day.
In patients with CTCL receiving an initial dose of 300 mg/m 2 /day, the incidence of NCI Grade 3 or 4 elevations in triglycerides and total cholesterol was 28% and 25%, respectively (Table 4).
In contrast, in patients with CTCL receiving greater than 300 mg/m 2 /day, the incidence of NCI Grade 3 or 4 elevated triglycerides and total cholesterol was 45% and 45%, respectively.
Other Grade 3 and 4 laboratory abnormalities are shown in Table 3.
In addition to the 152 patients enrolled in the two CTCL trials, 352 patients received bexarotene capsules as monotherapy for various advanced malignancies at doses from 5 mg/m 2 /day to 1000 mg/m 2 /day.
The common adverse reactions (incidence greater than 10%) were similar to those seen in patients with CTCL.
In the 504 patients (CTCL and non-CTCL) who received bexarotene capsules as monotherapy, drug-related serious adverse reactions that were fatal, in one patient each, were acute pancreatitis, subdural hematoma, and liver failure.
In the patients with CTCL receiving an initial dose of 300 mg/m 2 /day of bexarotene capsules, adverse reactions reported at an incidence of less than 10% and not included in Tables 2-4 or discussed in other parts of labeling and possibly related to treatment were as follows: Body as a Whole: chills, cellulitis, chest pain, breast pain, sepsis, and monilia infection.
Cardiovascular: hemorrhage, hypertension, angina pectoris, right heart failure, syncope, and tachycardia.
Digestive: constipation, dry mouth, flatulence, colitis, dyspepsia, cheilitis, gastroenteritis, gingivitis, liver failure, and melena.
Hemic and Lymphatic: eosinophilia, thrombocythemia, coagulation time increased, lymphocytosis, and thrombocytopenia.
Metabolic and Nutritional: LDH increased, creatinine increased, hypoproteinemia, hyperglycemia, weight decreased, weight increased, and amylase increased.
Musculoskeletal: arthralgia, myalgia, bone pain, myasthenia, and arthrosis.
Nervous: depression, agitation, ataxia, cerebrovascular accident, confusion, dizziness, hyperesthesia, hypesthesia, and neuropathy.
Respiratory : pharyngitis, rhinitis, dyspnea, pleural effusion, bronchitis, cough increased, lung edema, hemoptysis, and hypoxia.
Skin and Appendages: skin ulcer, acne, alopecia, skin nodule, macular papular rash, pustular rash, serous drainage, and vesicular bullous rash.
Special Senses: dry eyes, conjunctivitis, ear pain, blepharitis, corneal lesion, keratitis, otitis externa, and visual field defect.
Urogenital: albuminuria, hematuria, urinary incontinence, urinary tract infection, urinary urgency, dysuria, and kidney function abnormal.
Table 2: Adverse Events with Incidence ≥10% in CTCL Trials Body System Adverse Event 1,2 Initial Assigned Dose Group (mg/m 2 /day) 300 >300 N = 84 N (%) N = 53 N (%) METABOLIC AND NUTRITIONAL DISORDERS Hyperlipemia 66 (79) 42 (79) Hypercholesteremia 27 (32) 33 (62) Lactic dehydrogenase increased 6 (7) 7 (13) BODY AS A WHOLE Headache 25 (30) 22 (42) Asthenia 17 (20) 24 (45) Infection 11 (13) 12 (23) Abdominal pain 9 (11) 2 (4) Chills 8 (10) 7 (13) Fever 4 (5) 9 (17) Flu syndrome 3 (4) 7 (13) Back pain 2 (2) 6 (11) Infection bacterial 1 (1) 7 (13) ENDOCRINE Hypothyroidism 24 (29) 28 (53) SKIN AND APPENDAGES Rash 14 (17) 12 (23) Dry skin 9 (17) 5 (9) Exfoliative dermatitis 8 (10) 15 (28) Alopecia 3 (4) 6 (11) HEMIC AND LYMPHATIC SYSTEM Leukopenia 14 (17) 25 (47) Anemia 5 (6) 13 (25) Hypochromic anemia 3 (4) 7 (13) DIGESTIVE SYSTEM Nausea 13 (16) 4 (8) Diarrhea 6 (7) 22 (42) Vomiting 3 (4) 7 (13) Anorexia 2 (2) 12 (23) CARDIOVASCULAR SYSTEM Peripheral edema 11 (13) 6 (11) NERVOUS SYSTEM Insomnia 4 (5) 6 (11) 1 Preferred English term coded according to Ligand-modified COSTART 5 Dictionary.
2 Patients are counted at most once in each AE category.
Table 3: Incidence of Moderately Severe and Severe Adverse Events Reported in at Least Two Patients (CTCL Trials) Initial Assigned Dose Group (mg/m 2 /day) 300 (N = 84) >300 (N = 53) Mod Sev Severe Mod Sev Severe Body System Adverse Event 1,2 N (%) N (%) N (%) N (%) BODY AS A WHOLE Asthenia 1 (1) 0 (0) 11 (21) 0 (0) Headache 3 (4) 0 (0) 5 (9) 1 (2) Infection bacterial 1 (1) 0 (0) 0 (0) 2 (4) CARDIOVASCULAR SYS.
Peripheral edema 2 (2) 1 (1) 0 (0) 0 (0) DIGESTIVE SYSTEM Anorexia 0 (0) 0 (0) 3 (6) 0 (0) Diarrhea 1 (1) 1 (1) 2 (4) 1 (2) Pancreatitis 1 (1) 0 (0) 3 (6) 0 (0) Vomiting 0 (0) 0 (0) 2 (4) 0 (0) ENDOCRINE Hypothyroidism 1 (1) 1 (1) 2 (4) 0 (0) HEM.
& LYMPH.
SYS.
Leukopenia 3 (4) 0 (0) 6 (11) 1 (2) META.
AND NUTR.
DIS.
Bilirubinemia 0 (0) 1 (1) 2 (4) 0 (0) Hypercholesteremia 2 (2) 0 (0) 5 (9) 0 (0) Hyperlipemia 16 (19) 6 (7) 17 (32) 5 (9) SGOT/AST increased 0 (0) 0 (0) 2 (4) 0 (0) SGPT/ALT increased 0 (0) 0 (0) 2 (4) 0 (0) RESPIRATORY SYSTEM Pneumonia 0 (0) 0 (0) 2 (4) 2 (4) SKIN AND APPENDAGES Exfoliative dermatitis 0 (0) 1 (1) 3 (6) 1 (2) Rash 1 (1) 2 (2) 1 (2) 0 (0) 1 Preferred English term coded according to Ligand-modified COSTART 5 Dictionary.
2 Patients are counted at most once in each AE category.
Patients are classified by the highest severity within each row.
Table 4: Treatment-Emergent Abnormal Laboratory Values in CTCL Trials Initial Assigned Dose (mg/m 2 /day) 300 >300 N = 83 1 N = 53 1 Analyte Grade 3 2 (%) Grade 4 2 (%) Grade 3 (%) Grade 4 (%) Triglycerides 3 21 7 32 14 Total Cholesterol 3 19 7 16 30 Alkaline Phosphatase 1 0 0 2 Hyperglycemia 1 0 6 0 Hypocalcemia 1 0 0 0 Hyponatremia 1 0 9 0 SGPT/ALT 1 0 2 2 Hyperkalemia 0 0 2 0 Hypernatremia 0 1 0 0 SGOT/AST 0 0 2 2 Total Bilirubin 0 0 0 2 ANC decreased 12 4 19 8 ALC decreased 7 0 15 0 WBC decreased 4 0 11 0 Hemoglobin decreased 0 0 2 0 1 Number of patients with at least one analyte value post-baseline.
2 Adapted from NCI Common Toxicity Criteria, Grade 3 and 4, Version 2.0.
Patients are considered to have had a Grade 3 or 4 value if either of the following occurred: a) Value becomes Grade 3 or 4 during the study; b) Value is abnormal at baseline and worsens to Grade 3 or 4 on study, including all values beyond study drug discontinuation, as defined in data handling conventions.
3 The denominator used to calculate the incidence rates for fasting Total Cholesterol and Triglycerides were N=75 for the 300 mg/m 2 /day initial dose group and N=44 for the >300 mg/m 2 /day initial dose group.
The safety profile from the one post-approval trial with 59 subjects was generally comparable to that of the pivotal trials with the exception of serious adverse events hypertriglyceridemia, neutropenia and bone marrow failure which were observed more frequently in the bexarotene capsule 300 mg/m 2 /day group than in the bexarotene capsule 150 mg/m 2 /day group.
Severe hypertriglyceridemia (≥800 mg/dL) was not seen in any subject in the lower dosage arm.
The most common AEs by preferred term in either the bexarotene capsule 300 or 150 mg/m 2 /day treatment group were as follows: hypertriglyceridemia (18 subjects [62.1%] and 17 subjects [56.7%], respectively); hypothyroidism (15 subjects [51.7%] and 13 subjects [43.3%], respectively); headache (9 subjects [31.0%] and 7 subjects [23.3%], respectively); hypercholesterolemia (8 subjects [27.6%] and 7 subjects [23.3%], respectively); neutropenia (7 subjects [24.1%] and 2 subjects [6.7%], respectively); and skin exfoliation (5 subjects [17.2%] and 5 subjects [16.7%], respectively).
Higher percentage of subjects in the bexarotene capsule 300 mg/m 2 /day group than in bexarotene capsule 150 mg/m 2 /day group experienced SAEs (13 subjects [44.8%] vs 11 subjects [36.7%], respectively.
Of the SAEs of special interest, there were more events in the bexarotene capsule 300 mg/m 2 /day group than in the bexarotene capsule 150 mg/m 2 /day group of bone marrow failure (3 [10.3%] vs 1 [3.3%, respectively]), neutropenia (3 [10.3%] vs 0 [0%], respectively), and of hypertriglyceridemia (9 [31%] vs 2 [6.7%], respectively).
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc.
at 1-855-204-1431 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 safety of bexarotene has been evaluated in two clinical trials of 152 patients with CTCL who received bexarotene capsules for up to 97 weeks and in 352 patients in other trials.
The mean duration of therapy for the 152 patients with CTCL was 166 days.
The most common adverse events reported with an incidence of at least 10% in patients with CTCL treated at an initial dose of 300 mg/m 2 /day of bexarotene capsules are shown in Table 2.
The events at least possibly related to treatment are lipid abnormalities (elevated triglycerides, elevated total and LDL cholesterol and decreased HDL cholesterol), hypothyroidism, headache, asthenia, rash, leukopenia, anemia, nausea, infection, peripheral edema, abdominal pain, and dry skin.
Most adverse events occurred at a greater incidence in patients treated at starting doses of greater than 300 mg/m 2 /day (see Table 2).
Adverse reactions leading to bexarotene capsule dose reduction or discontinuation in at least two patients were hyperlipemia, neutropenia/leukopenia, diarrhea, fatigue/lethargy, hypothyroidism, headache, liver function test abnormalities, rash, pancreatitis, nausea, anemia, allergic reaction, muscle spasm, pneumonia, and confusion.
The NCI Grade 3 and NCI Grade 4 adverse reactions reported in two or more patients with CTCL treated at an initial dose of 300 mg/m 2 /day of bexarotene capsules (see Table 3) were hypertriglyceridemia, pruritus, headache, peripheral edema, leukopenia, rash, and hypercholesteremia.
Most of these moderately severe or severe adverse events occurred at a higher rate in patients treated at starting doses of greater than 300 mg/m 2 /day than in patients treated at a starting dose of 300 mg/m 2 /day.
In patients with CTCL receiving an initial dose of 300 mg/m 2 /day, the incidence of NCI Grade 3 or 4 elevations in triglycerides and total cholesterol was 28% and 25%, respectively (Table 4).
In contrast, in patients with CTCL receiving greater than 300 mg/m 2 /day, the incidence of NCI Grade 3 or 4 elevated triglycerides and total cholesterol was 45% and 45%, respectively.
Other Grade 3 and 4 laboratory abnormalities are shown in Table 3.
In addition to the 152 patients enrolled in the two CTCL trials, 352 patients received bexarotene capsules as monotherapy for various advanced malignancies at doses from 5 mg/m 2 /day to 1000 mg/m 2 /day.
The common adverse reactions (incidence greater than 10%) were similar to those seen in patients with CTCL.
In the 504 patients (CTCL and non-CTCL) who received bexarotene capsules as monotherapy, drug-related serious adverse reactions that were fatal, in one patient each, were acute pancreatitis, subdural hematoma, and liver failure.
In the patients with CTCL receiving an initial dose of 300 mg/m 2 /day of bexarotene capsules, adverse reactions reported at an incidence of less than 10% and not included in Tables 2-4 or discussed in other parts of labeling and possibly related to treatment were as follows: Body as a Whole: chills, cellulitis, chest pain, breast pain, sepsis, and monilia infection.
Cardiovascular: hemorrhage, hypertension, angina pectoris, right heart failure, syncope, and tachycardia.
Digestive: constipation, dry mouth, flatulence, colitis, dyspepsia, cheilitis, gastroenteritis, gingivitis, liver failure, and melena.
Hemic and Lymphatic: eosinophilia, thrombocythemia, coagulation time increased, lymphocytosis, and thrombocytopenia.
Metabolic and Nutritional: LDH increased, creatinine increased, hypoproteinemia, hyperglycemia, weight decreased, weight increased, and amylase increased.
Musculoskeletal: arthralgia, myalgia, bone pain, myasthenia, and arthrosis.
Nervous: depression, agitation, ataxia, cerebrovascular accident, confusion, dizziness, hyperesthesia, hypesthesia, and neuropathy.
Respiratory : pharyngitis, rhinitis, dyspnea, pleural effusion, bronchitis, cough increased, lung edema, hemoptysis, and hypoxia.
Skin and Appendages: skin ulcer, acne, alopecia, skin nodule, macular papular rash, pustular rash, serous drainage, and vesicular bullous rash.
Special Senses: dry eyes, conjunctivitis, ear pain, blepharitis, corneal lesion, keratitis, otitis externa, and visual field defect.
Urogenital: albuminuria, hematuria, urinary incontinence, urinary tract infection, urinary urgency, dysuria, and kidney function abnormal.
Table 2: Adverse Events with Incidence ≥10% in CTCL Trials Body System Adverse Event 1,2 Initial Assigned Dose Group (mg/m 2 /day) 300 >300 N = 84 N (%) N = 53 N (%) METABOLIC AND NUTRITIONAL DISORDERS Hyperlipemia 66 (79) 42 (79) Hypercholesteremia 27 (32) 33 (62) Lactic dehydrogenase increased 6 (7) 7 (13) BODY AS A WHOLE Headache 25 (30) 22 (42) Asthenia 17 (20) 24 (45) Infection 11 (13) 12 (23) Abdominal pain 9 (11) 2 (4) Chills 8 (10) 7 (13) Fever 4 (5) 9 (17) Flu syndrome 3 (4) 7 (13) Back pain 2 (2) 6 (11) Infection bacterial 1 (1) 7 (13) ENDOCRINE Hypothyroidism 24 (29) 28 (53) SKIN AND APPENDAGES Rash 14 (17) 12 (23) Dry skin 9 (17) 5 (9) Exfoliative dermatitis 8 (10) 15 (28) Alopecia 3 (4) 6 (11) HEMIC AND LYMPHATIC SYSTEM Leukopenia 14 (17) 25 (47) Anemia 5 (6) 13 (25) Hypochromic anemia 3 (4) 7 (13) DIGESTIVE SYSTEM Nausea 13 (16) 4 (8) Diarrhea 6 (7) 22 (42) Vomiting 3 (4) 7 (13) Anorexia 2 (2) 12 (23) CARDIOVASCULAR SYSTEM Peripheral edema 11 (13) 6 (11) NERVOUS SYSTEM Insomnia 4 (5) 6 (11) 1 Preferred English term coded according to Ligand-modified COSTART 5 Dictionary.
2 Patients are counted at most once in each AE category.
Table 3: Incidence of Moderately Severe and Severe Adverse Events Reported in at Least Two Patients (CTCL Trials) Initial Assigned Dose Group (mg/m 2 /day) 300 (N = 84) >300 (N = 53) Mod Sev Severe Mod Sev Severe Body System Adverse Event 1,2 N (%) N (%) N (%) N (%) BODY AS A WHOLE Asthenia 1 (1) 0 (0) 11 (21) 0 (0) Headache 3 (4) 0 (0) 5 (9) 1 (2) Infection bacterial 1 (1) 0 (0) 0 (0) 2 (4) CARDIOVASCULAR SYS.
Peripheral edema 2 (2) 1 (1) 0 (0) 0 (0) DIGESTIVE SYSTEM Anorexia 0 (0) 0 (0) 3 (6) 0 (0) Diarrhea 1 (1) 1 (1) 2 (4) 1 (2) Pancreatitis 1 (1) 0 (0) 3 (6) 0 (0) Vomiting 0 (0) 0 (0) 2 (4) 0 (0) ENDOCRINE Hypothyroidism 1 (1) 1 (1) 2 (4) 0 (0) HEM.
& LYMPH.
SYS.
Leukopenia 3 (4) 0 (0) 6 (11) 1 (2) META.
AND NUTR.
DIS.
Bilirubinemia 0 (0) 1 (1) 2 (4) 0 (0) Hypercholesteremia 2 (2) 0 (0) 5 (9) 0 (0) Hyperlipemia 16 (19) 6 (7) 17 (32) 5 (9) SGOT/AST increased 0 (0) 0 (0) 2 (4) 0 (0) SGPT/ALT increased 0 (0) 0 (0) 2 (4) 0 (0) RESPIRATORY SYSTEM Pneumonia 0 (0) 0 (0) 2 (4) 2 (4) SKIN AND APPENDAGES Exfoliative dermatitis 0 (0) 1 (1) 3 (6) 1 (2) Rash 1 (1) 2 (2) 1 (2) 0 (0) 1 Preferred English term coded according to Ligand-modified COSTART 5 Dictionary.
2 Patients are counted at most once in each AE category.
Patients are classified by the highest severity within each row.
Table 4: Treatment-Emergent Abnormal Laboratory Values in CTCL Trials Initial Assigned Dose (mg/m 2 /day) 300 >300 N = 83 1 N = 53 1 Analyte Grade 3 2 (%) Grade 4 2 (%) Grade 3 (%) Grade 4 (%) Triglycerides 3 21 7 32 14 Total Cholesterol 3 19 7 16 30 Alkaline Phosphatase 1 0 0 2 Hyperglycemia 1 0 6 0 Hypocalcemia 1 0 0 0 Hyponatremia 1 0 9 0 SGPT/ALT 1 0 2 2 Hyperkalemia 0 0 2 0 Hypernatremia 0 1 0 0 SGOT/AST 0 0 2 2 Total Bilirubin 0 0 0 2 ANC decreased 12 4 19 8 ALC decreased 7 0 15 0 WBC decreased 4 0 11 0 Hemoglobin decreased 0 0 2 0 1 Number of patients with at least one analyte value post-baseline.
2 Adapted from NCI Common Toxicity Criteria, Grade 3 and 4, Version 2.0.
Patients are considered to have had a Grade 3 or 4 value if either of the following occurred: a) Value becomes Grade 3 or 4 during the study; b) Value is abnormal at baseline and worsens to Grade 3 or 4 on study, including all values beyond study drug discontinuation, as defined in data handling conventions.
3 The denominator used to calculate the incidence rates for fasting Total Cholesterol and Triglycerides were N=75 for the 300 mg/m 2 /day initial dose group and N=44 for the >300 mg/m 2 /day initial dose group.
The safety profile from the one post-approval trial with 59 subjects was generally comparable to that of the pivotal trials with the exception of serious adverse events hypertriglyceridemia, neutropenia and bone marrow failure which were observed more frequently in the bexarotene capsule 300 mg/m 2 /day group than in the bexarotene capsule 150 mg/m 2 /day group.
Severe hypertriglyceridemia (≥800 mg/dL) was not seen in any subject in the lower dosage arm.
The most common AEs by preferred term in either the bexarotene capsule 300 or 150 mg/m 2 /day treatment group were as follows: hypertriglyceridemia (18 subjects [62.1%] and 17 subjects [56.7%], respectively); hypothyroidism (15 subjects [51.7%] and 13 subjects [43.3%], respectively); headache (9 subjects [31.0%] and 7 subjects [23.3%], respectively); hypercholesterolemia (8 subjects [27.6%] and 7 subjects [23.3%], respectively); neutropenia (7 subjects [24.1%] and 2 subjects [6.7%], respectively); and skin exfoliation (5 subjects [17.2%] and 5 subjects [16.7%], respectively).
Higher percentage of subjects in the bexarotene capsule 300 mg/m 2 /day group than in bexarotene capsule 150 mg/m 2 /day group experienced SAEs (13 subjects [44.8%] vs 11 subjects [36.7%], respectively.
Of the SAEs of special interest, there were more events in the bexarotene capsule 300 mg/m 2 /day group than in the bexarotene capsule 150 mg/m 2 /day group of bone marrow failure (3 [10.3%] vs 1 [3.3%, respectively]), neutropenia (3 [10.3%] vs 0 [0%], respectively), and of hypertriglyceridemia (9 [31%] vs 2 [6.7%], respectively).