ysgeusia, dry mouth). The most common serious drug-related adverse reactions were pulmonary embolism and anemia.
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 ZOLINZA was eva luated in 107 CTCL patients in two single arm clinical studies in which 86 patients received 400 mg once daily.
The data described below reflect exposure to ZOLINZA 400 mg once daily in the 86 patients for a median number of 97.5 days on therapy (range 2 to 480+ days). Seventeen (19.8%) patients were exposed beyond 24 weeks and 8 (9.3%) patients were exposed beyond 1 year. The population of CTCL patients studied was 37 to 83 years of age, 47.7% female, 52.3% male, and 81.4% white, 16.3% black, and 1.2% Asian or multi-racial.
Common Adverse Reactions
Table 1 summarizes the frequency of CTCL patients with specific adverse reactions, using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 3.0).
Table 1: Clinical or Laboratory Adverse Reactions Occurring in CTCL Patients (Incidence ≥10% of patients) ZOLINZA 400 mg once daily (N=86)
Adverse Reactions All Grades Grades 3-5*
n % n %
*
No Grade 5 reactions were reported.
Fatigue 45 52.3 3 3.5
Diarrhea 45 52.3 0 0.0
Nausea 35 40.7 3 3.5
Dysgeusia 24 27.9 0 0.0
Thrombocytopenia 22 25.6 5 5.8
Anorexia 21 24.4 2 2.3
Weight Decreased 18 20.9 1 1.2
Muscle Spasms 17 19.8 2 2.3
Alopecia 16 18.6 0 0.0
Dry Mouth 14 16.3 0 0.0
Blood Creatinine Increased 14 16.3 0 0.0
Chills 14 16.3 1 1.2
Vomiting 13 15.1 1 1.2
Constipation 13 15.1 0 0.0
Dizziness 13 15.1 1 1.2
Anemia 12 14.0 2 2.3
Decreased Appetite 12 14.0 1 1.2
Peripheral Edema 11 12.8 0 0.0
Headache 10 11.6 0 0.0
Pruritus 10 11.6 1 1.2
Cough 9 10.5 0 0.0
Upper Respiratory Infection 9 10.5 0 0.0
Pyrexia 9 10.5 1 1.2
The frequencies of more severe thrombocytopenia, anemia [see Warnings and Precautions (5.2)] and fatigue were increased at doses higher than 400 mg once daily of ZOLINZA.
Serious Adverse Reactions
The most common serious adverse reactions in the 86 CTCL patients in two clinical trials were pulmonary embolism reported in 4.7% (4/86) of patients, squamous cell carcinoma reported in 3.5% (3/86) of patients and anemia reported in 2.3% (2/86) of patients. There were single events of cholecystitis, death (of unknown cause), deep vein thrombosis, enterococcal infection, exfoliative dermatitis, gastrointestinal hemorrhage, infection, lobar pneumonia, myocardial infarction, ischemic stroke, pelviureteric obstruction, sepsis, spinal cord injury, streptococcal bacteremia, syncope, T-cell lymphoma, thrombocytopenia and ureteric obstruction.
Discontinuations
Of the CTCL patients who received the 400-mg once daily dose, 9.3% (8/86) of patients discontinued ZOLINZA due to adverse reactions. These adverse reactions, regardless of causality, included anemia, angioneurotic edema, asthenia, chest pain, exfoliative dermatitis, death, deep vein thrombosis, ischemic stroke, lethargy, pulmonary embolism, and spinal cord injury.
Dose Modifications
Of the CTCL patients who received the 400-mg once daily dose, 10.5% (9/86) of patients required a dose modification of Z
