Randomized open-label trial of intravenous brivaracetam versus lorazepam for acute treatment of increased seizure activity.

OBJECTIVE: The objective of the present trial was to assess efficacy and safety of intravenous (IV) brivaracetam (BRV) vs. lorazepam (LZP) in patients with epilepsy undergoing evaluation in an epilepsy monitoring unit (EMU) who experienced seizures requiring acute treatment. METHODS: This was a phase 2, open-label, randomized, active-control, proof-of-concept trial (EP0087; NCT03021018). Patients (18-70 years) admitted to EMU were randomized 1:1:1 to single-dose bolus IV LZP (dose per investigator's practice), IV BRV 100 mg, or IV BRV 200 mg. Trial medication had to be administered within 30 min of qualifying seizure. Primary efficacy outcome was time to next seizure (clinical observation with electroencephalogram [EEG] confirmation) or to rescue medication use within 12 h of trial medication administration. Secondary outcomes included seizure freedom and rescue medication use within 12 h of trial medication administration. Safety and tolerability outcomes included treatment-emergent adverse events (TEAEs). RESULTS: Overall, 46 patients were randomized, and 45 received trial medication for a qualifying seizure. Patients in the LZP arm had doses from 1 to 4 mg (median: 1 mg). Eleven of 45 patients had a seizure within 12 h of trial medication administration (LZP 5/15 [median time to next seizure: 5.55 h], BRV 100 mg 3/15 [5.97 h], BRV 200 mg 3/15 [3.60 h]). No patients received additional rescue medication to control their qualifying seizure. Most patients were seizure-free over 12 h (LZP 9/15 [60.0%], BRV 100 mg 12/15 [80.0%], BRV 200 mg 12/15 [80.0%]). Rescue medication use within 12 h was numerically higher for LZP (6/15 [40.0%]) vs. BRV 100 mg (1/15 [6.7%]) and vs. BRV 200 mg (2/15 [13.3%]). Treatment-emergent adverse events were reported by 5/16 (31.3%), 6/15 (40.0%), and 3/15 (20.0%) of LZP, BRV 100 mg, and BRV 200 mg patients; one LZP patient had a serious TEAE (seizure cluster). Most common TEAEs (≥10% of patients) were sedation and somnolence with LZP, and dizziness, headache, and nausea with BRV. SIGNIFICANCE: Intravenous LZP, IV BRV 100 mg, and IV BRV 200 mg showed similar efficacy in controlling acute seizure activity in the EMU. Treatment-emergent adverse events were as expected for each medication. Although this trial should be interpreted with caution because of small patient numbers, it suggests a possible role of BRV in the acute treatment of increased seizure activity.

Validation of the revised Patient Perception of Migraine Questionnaire: measuring satisfaction with acute migraine treatment.

OBJECTIVE: To evaluate the psychometric properties of the revised Patient Perception of Migraine Questionnaire (PPMQ-R), which measures satisfaction with migraine treatment. BACKGROUND: The original version of the PPMQ was developed prior to the introduction of newer migraine treatments, which may have attributes that influence treatment satisfaction. METHODS: Literature review, patient focus groups, and one-on-one patient interviews guided revisions to the original PPMQ. The revised questionnaire was tested in 200 migraine patients visiting neurologists and primary care clinics. At baseline, all subjects completed the PPMQ-R, a migraine-specific quality-of-life measure, and a migraine experience questionnaire; and 125 subjects completed assessments 24 hours after each migraine attack and within 30 days post-baseline. Factor analysis was performed to inform the development of a scoring algorithm, and reliability, validity, and responsiveness of the PPMQ-R were evaluated. RESULTS: Factor analyses confirmed that the revised questionnaire has five domains measuring satisfaction with efficacy, functionality, ease of use, medication cost, and bothersomeness of medication side effects. A total score can be created by taking the average of efficacy, functionality, and ease of use scores. The PPMQ-R scale scores and Total score demonstrated internal consistency reliability (Cronbach's alpha: 0.80 to 0.98) and test-retest reliability (intra-class correlation coefficient: 0.79 to 0.91). Except for the Cost domain, the PPMQ-R scores discriminated among migraine pain severity levels (all P < .05) and levels of impairment in ability to work and perform usual activities (all P < .05). Except for the Ease of Use and Cost domains, mean PPMQ-R scores were significantly higher among patients with no change in treatment and whose pain improved between two consecutive migraine attacks (all P < .01). CONCLUSION: The PPMQ-R is a reliable and valid measure of patient satisfaction with acute migraine treatment in women with frequent migraine attacks.