TROKENDI XR Rx

Preventive Treatment of Migraine 

Adult Patients

• The efficacy of immediate-release topiramate in the preventive treatment of migraine was evaluated in 2 identical, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trials conducted in the US (Study 11) or the US and Canada (Study 12).

• The trials included patients with a history of migraine with or without aura for at least 6 months. Patients were required to have completed up to a 2-week washout of any prior migraine preventative medications before starting the baseline phase.

• Patients who experienced 3 to 12 migraine headaches over the 4 weeks in the baseline phase were randomly assigned to either immediate-release topiramate 50mg/day, 100mg/day, 200mg/day or placebo for a total of 26 weeks. Effectiveness was assessed by the reduction in migraine headache frequency, as measured by the change in 4-week migraine rate from the baseline phase to double-blind period.

• In Study 11, the change in the mean 4-week migraine headache frequency from baseline to the double-blind phase was -1.3, -2.1, and -2.2 in the topiramate 50mg/day, 100mg/day, and 200mg/day treatment arms vs -0.8 in the placebo arm. The placebo-adjusted treatment differences for the 100mg and 200mg arms were similar and statistically significant (P <.001 for both).

• In Study 12, the change in the mean 4-week migraine headache frequency from baseline to the double-blind phase was -1.4, -2.1, and -2.4 in the topiramate 50mg/day, 100mg/day, and 200mg/day treatment arms vs -1.1 in the placebo arm. The placebo-adjusted treatment differences for the 100mg and 200mg arms were similar and statistically significant (P =.008 and P <.001, respectively).

Pediatric Patients 12 to 17 Years of Age 

• The efficacy of immediate-release topiramate in the preventive treatment of migraine was evaluated in a multicenter, randomized, double-blind, parallel-group clinical trial (Study 13).

• The trials included patients 12 to 17 years of age with episodic migraine headaches with or without aura. Patients who experienced 3 to 12 migraine attacks and ≤14 headache days during the 4-week prospective baseline period over the 4 weeks in the baseline phase were randomly assigned to either immediate-release topiramate 50mg/day, 100mg/day or placebo for a total of 16 weeks. Effectiveness was assessed by the percent reduction from baseline to the last 12 weeks of the double-blind phase in the monthly migraine attack rate.

• In Study 13, patients treated with topiramate 100mg/day achieved a 72.2% median reduction in the monthly migraine attack rate vs 44.4% median reduction for patients treated with placebo (P =.0164).

• The mean reduction from baseline to the last 12 weeks of the double-blind phase in average monthly attack rate was 3.0 for 100mg and 1.7 for placebo (treatment difference, 1.3; P =.0087).

Monotherapy Epilepsy

Patients With Partial-Onset or Primary Generalized Tonic-Clonic Seizures (Patients Aged ≥10yrs)

• The efficacy of topiramate as initial monotherapy in adults and pediatric patients10 years of age and older with partial onset or primary generalized tonic-clonic seizures in a multicenter, randomized, double-blind, dose-controlled, parallel-group trial (Study 1).

• Study 1 included 487 patients diagnosed with epilepsy who were randomly assigned to titrate up to 50mg/day or 400mg/day of topiramate. The primary endpoint was a between-group comparison of time to first seizure during the double-blind phase.

• Results showed that the treatment effects with respect to time to first seizure were consistent across various patient subgroups defined by age, sex, geographic region, baseline body weight, baseline seizure type, time since diagnosis, and baseline AED use.

Patients With Partial-Onset or Primary Generalized Tonic-Clonic Seizures (Pediatric Patients 6 to 9 Years of Age)

• Topiramate was found to be effective as initial monotherapy in pediatric patients 6 to 9 years of age with partial-onset or primary generalized tonic-clonic seizures based on a pharmacometric bridging approach using data from the controlled epilepsy trials conducted with immediate-release topiramate.

Adjunctive Therapy Epilepsy 

Adult Patients With Partial-Onset Seizures

• The efficacy of topiramate as an adjunctive treatment for adults with a history of partial-onset seizures, with or without secondarily generalized seizures, was established in 6 multicenter, randomized, double-blind, placebo-controlled trials (Studies 2, 3, 4, 5, 6, and 7). In 2 of the studies, several doses of topiramate were compared with placebo. In 4 of the studies, a single dosage of topiramate was compared with placebo.

• In these studies, patients were allowed to take a maximum of 2 antiepileptic drugs (AEDs) in addition to topiramate or placebo. Patients who experienced a prespecified minimum number of partial-onset seizures with or without secondary generalized seizures during the baseline phase were randomly assigned to receive either placebo or a specified dose of topiramate in addition to their AEDs.

• The median percent reductions in seizure rates and the responder rates (fraction of patients with at least a 50% reduction) for topiramate and placebo were measured.

• Study 2: 

• Median % reduction:

• 27% for 200mg/day; 48% for 400mg/day; 45% for 600mg/day vs 12% for placebo

• % responders: 

• 24% for 200mg/day; 44% for 400mg/day; 46% for 600mg/day vs 18% for placebo

• Study 3: 

• Median % reduction:

• 48% for 600mg/day; 48% for 800mg/day; 47% for 1000mg/day vs 2% for placebo

• % responders: 

• 40% for 600mg/day; 41% for 800mg/day; 36% for 1000mg/day vs 9% for placebo

• Study 4: 

• Median % reduction:

• 41% for 400mg/day vs 1% for placebo

• % responders: 

• 35% for 400mg/day vs 8% for placebo

• Study 5: 

• Median % reduction:

• 46% for 600mg/day vs -12% for placebo

• % responders: 

• 47% for 600mg/day vs 10% for placebo

• Study 6: 

• Median % reduction:

• 24% for 800mg/day vs -21% for placebo

• % responders: 

• 43% for 800mg/day vs 0% for placebo

• Study 7: 

• Median % reduction:

• 44% for 200mg/day vs 20% for placebo

• % responders: 

• 45% for 200mg/day vs 24% for placebo

Pediatric Patients 6 to 16 Years of Age With Partial-Onset Seizures

• The efficacy of topiramate as an adjunctive treatment for pediatric patients 6 to 16 years of age with a history of partial-onset seizures, with or without secondarily generalized seizures, was established in a multicenter, randomized, double-blind, placebo-controlled trials (Study 8).

• In the study, patients were allowed to take a maximum of 2 AEDs in addition to topiramate or placebo. Patients whoexperienced at least 6 partial-onset seizures with or without secondary generalized seizures during the baseline phase were randomly assigned to receive either placebo or a specified dose of topiramate in addition to their AEDs.

• The median percent reductions in seizure rates and the responder rates (fraction of patients with at least a 50% reduction) for topiramate and placebo were measured.

• Study 8: 

• Median % reduction:

• 33% for 6mg/kg/day vs 11% for placebo

• % responders: 

• 39% for 6mg/kg/day vs 20% for placebo

Patients With Primary Generalized Tonic-Clonic Seizures

• The efficacy of topiramate as an adjunctive treatment for patients 6 years of age and older with primary generalized tonic-clonic seizures was established in a multicenter, randomized, double-blind, placebo-controlled trial (Study 9).

• In the study, patients were allowed to take a maximum of 2 AEDs in addition to topiramate or placebo. Patients who experienced at least 3 primary generalized tonic-clonic seizures during the baseline phase were randomly assigned to receive either placebo or a specified dose of topiramate in addition to their AEDs.

• The median percent reductions in seizure rates and the responder rates (fraction of patients with at least a 50% reduction) for topiramate and placebo were measured.

• Study 9: 

• Median % reduction:

• 57% for 6mg/kg/day vs 9% for placebo

• % responders: 

• 56% for 6mg/kg/day vs 20% for placebo

Patients With Lennox-Gastaut Syndrome

• The efficacy of topiramate as an adjunctive treatment for patients 6 years of age and older with seizures associated with Lennox-Gastaut syndrome was established in a multicenter, randomized, double-blind, placebo-controlled trial (Study 10).

• In the study, patients were allowed to take a maximum of 2 AEDs in addition to topiramate or placebo. Patients who experienced at least 60 seizures per month before study entry.

• The median percent reductions in seizure rates and the responder rates (fraction of patients with at least a 50% reduction) for topiramate and placebo were measured.

• Study 10: 

• Median % reduction:

• 15% for 6mg/kg/day vs -5% for placebo

• % responders: 

• 28% for 6mg/kg/day vs 14% for placebo

• Improvement in Seizure Severity:

• 52% for 6mg/kg/day vs 28% for placebo