Skip to main content

Controlled Trials

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.

Placebo-controlled double-blind studies were performed in adults and in pediatric patients, down to age of 4, in other forms of epilepsy, in addition to the trial in Lennox-Gastaut syndrome. Data on CNS Reactions [see WARNINGS AND PRECAUTIONS] from the Lennox-Gastaut study are presented first. Because there is no reason to suspect that adverse reactions would substantially differ between these patient populations, safety data from all of these controlled studies are then presented. Most of these adverse reactions were mild to moderate and transient in nature.

Common central nervous system reactions in the controlled trial of patients 4 years or older with Lennox-Gastaut syndrome treated with BANZEL (rufinamide tablets) as adjunctive therapy [see WARNINGS AND PRECAUTIONS]

Somnolence was reported in 24.3% of BANZEL (rufinamide tablets) -treated patients compared to 12.5% of placebo patients and led to study discontinuation in 2.7% of treated patients compared to 0% of placebo patients. Fatigue was reported in 9.5% of BANZEL (rufinamide tablets) -treated patients compared to 7.8% of placebo patients. It led to study discontinuation in 1.4% of treated patients and 0% of placebo patients.

Dizziness was reported in 2.7% of BANZEL (rufinamide tablets) -treated patients compared to 0% of placebo patients, and did not lead to study discontinuation.

Ataxia and gait disturbance were reported in 5.4% and 1.4% of BANZEL (rufinamide tablets) -treated patients, respectively, and in no placebo patients. Balance disorder and abnormal coordination were each reported in 0% of BANZEL (rufinamide tablets) -treated patients and 1.6% of placebo patients. None of these reactions led to study discontinuation.

All Adverse Reactions for All Treated Patients with Epilepsy, Double-blind Adjunctive Therapy Studies: The most commonly observed ( ≥ 10%) adverse reactions in BANZEL (rufinamide tablets) -treated patients, when used as adjunctive therapy at all doses studied (200 to 3200 mg/day) with a higher frequency than in placebo were: headache, dizziness, fatigue, somnolence, and nausea.

Table 2 lists treatment-emergent adverse reactions that occurred in at least 3% of pediatric patients with epilepsy treated with BANZEL (rufinamide tablets) in controlled adjunctive studies and were numerically more common in patients treated with BANZEL (rufinamide tablets) than placebo.

At the target dose of 45 mg/kg/day for adjunctive therapy in children, the most commonly observed ( ≥ 3%) adverse reactions with an incidence greater than in placebo, for BANZEL (rufinamide tablets) were somnolence, vomiting and headache.

Table 2: Incidence (%) of Treatment-Emergent Adverse Reactions in all Pediatric Double-Blind Adjunctive Trials by Preferred Term at the Recommended Dose of 45 mg/kg/day (Adverse Reactions occurred in at least 3% of BANZEL (rufinamide tablets) -treated patients and occurred more frequently than in Placebo Patients)

Preferred Term BANZEL (rufinamide tablets)
(N=187)
%
Placebo
(N=182)
%
Somnolence 17 9
Vomiting 17 7
Headache 16 8
Fatigue 9 8
Dizziness 8 6
Nausea 7 3
Influenza 5 4
Nasopharyngitis 5 3
Decreased Appetite 5 2
Rash 4 2
Ataxia 4 1
Diplopia 4 1
Bronchitis 3 2
Sinusitis 3 2
Psychomotor Hyperactivity 3 1
Abdominal Pain Upper 3 2
Aggression 3 2
Ear Infection 3 1
Disturbance in Attention 3 1
Pruritis 3 0

Table 3 lists treatment-emergent adverse reactions that occurred in at least 3% of adult patients with epilepsy treated with BANZEL (rufinamide tablets) (up to 3200mg/day) in adjunctive controlled studies and were numerically more common in patients treated with BANZEL (rufinamide tablets) than placebo. In these studies, either BANZEL (rufinamide tablets) or placebo was added to current AED therapy.

At all doses studied of up to 3200 mg/day given as adjunctive therapy in adults, the most commonly observed ( ≥ 3%) adverse reactions, and with the greatest increase in incidence compared to placebo, for BANZEL (rufinamide tablets) were dizziness, fatigue, nausea, diplopia, vision blurred, and ataxia.

Table 3: Incidence (%) of Treatment-Emergent Adverse Reactions in all Adult Double-Blind Adjunctive Trials (up to 3200mg/day) by Preferred Term (Adverse Reactions occurred in at least 3% of BANZEL (rufinamide tablets) -treated patients and occurred more frequently than in Placebo Patients)

Preferred Term BANZEL (rufinamide tablets)
(N=823)
%
Placebo
(N=376)
%
Headache 27 26
Dizziness 19 12
Fatigue 16 10
Nausea 12 9
Somnolence 11 9
Diplopia 9 3
Tremor 6 5
Nystagmus 6 5
Vision Blurred 6 2
Vomiting 5 4
Ataxia 4 0
Abdominal Pain Upper 3 2
Anxiety 3 2
Constipation 3 2
Dyspepsia 3 2
Back Pain 3 1
Gait Disturbance 3 1
Vertigo 3 1

Discontinuation in Controlled Clinical Studies

In controlled double-blind adjunctive clinical studies, 9.0% of patients receiving BANZEL (rufinamide tablets) as adjunctive therapy and 4.4% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of BANZEL (rufinamide tablets) ( > 1%) used as adjunctive therapy were generally similar in adults and children.

In pediatric double-blind adjunctive clinical studies, 8.0% of patients receiving BANZEL (rufinamide tablets) as adjunctive therapy and 2.2% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of BANZEL (rufinamide tablets) ( > 1%) used as adjunctive therapy are presented in Table 4.

Table 4: Adverse Reactions Most Commonly Leading to Discontinuation in Double-Blind Adjunctive Trials (At The Recommended Dose of 45mg/kg/day) in Pediatric Patients

Preferred Term BANZEL (rufinamide tablets)
(N=187)
%
Placebo
(N=182)
%
Convulsion 2 1
Rash 2 1
Fatigue 2 0
Vomiting 1 0

In adult double-blind adjunctive clinical studies (up to 3200 mg/day), 9.5% of patients receiving BANZEL (rufinamide tablets) as adjunctive therapy and 5.9% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions most commonly leading to discontinuation of BANZEL (rufinamide tablets) ( > 1%) used as adjunctive therapy are presented in Table 5.

Table 5: Adverse Reactions Most Commonly Leading to Discontinuation in Double-Blind Adjunctive Trials (up to 3200 mg/day) in Adult Patients

Preferred Term BANZEL (rufinamide tablets)
(N=823)
%
Placebo
(N=376)
%
Dizziness 3 1
Fatigue 2 1
Headache 2 1
Nausea 1 0
Ataxia 1 0

Other Adverse Events Observed During Clinical Trials

BANZEL (rufinamide tablets) has been administered to 1978 individuals during all epilepsy clinical trials (placebo­controlled and open-label). Adverse events occurring during these studies were recorded by the investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of patients having adverse events, these events were grouped into standardized categories using the MedDRA dictionary. Adverse events occurring at least three times and considered possibly related to treatment are included in the System Organ Class listings below. Terms not included in the listings are those already included in the tables above, those too general to be informative, those related to procedures and terms describing events common in the population. Some events occurring fewer than 3 times are also included based on their medical significance. Because the reports include events observed in open-label, uncontrolled observations, the role of BANZEL (rufinamide tablets) in their causation cannot be reliably determined.

Events are classified by body system and listed in order of decreasing frequency as follows: frequent adverse events- those occurring in at least 1/100 patients; infrequent adverse events-those occurring in 1/100 to 1/1000 patients; rare- those occurring in fewer than 1/1000 patients. Blood and Lymphatic System Disorders: Frequent: anemia. Infrequent: lymphadenopathy, leukopenia, neutropenia, iron deficiency anemia, thrombocytopenia. Cardiac Disorders: Infrequent: bundle branch block right, atrioventricular block first degree. Metabolic and Nutritional Disorders: Frequent: decreased appetite, increased appetite. Renal and Urinary Disorders: Frequent: pollakiuria. Infrequent: urinary incontinence, dysuria, hematuria, nephrolithiasis, polyuria, enuresis, nocturia, incontinence.