Long-term Safety and Efficacy of Adjunctive Brivaracetam in Chinese Patients With Uncontrolled Focal Epilepsy

Background and Rationale： Epilepsy is a neurological disorder characterized by recurrent, unprovoked seizures resulting from abnormal, excessive, or synchronous neuronal activity in the brain. Clinical manifestations include myoclonus, sudden interruption of psychomotor activity, loss of consciousness, sensory abnormalities, and emotional or psychomotor disturbances. In severe cases, sudden loss of consciousness with tonic-clonic convulsions may occur, accompanied by screaming, cyanosis, foaming at the mouth, and pupillary dilation. Status epilepticus, characterized by continuous seizure activity, can be life-threatening.

Brivaracetam tablets are a derivative of the second-generation antiepileptic drug levetiracetam, with a propyl group attached to the 4-position carbon of the pyrrolidine ring. Brivaracetam exerts its antiepileptic effect by binding to synaptic vesicle protein 2A (SV2A) in presynaptic nerve terminals, with 15 to 30 times higher affinity than levetiracetam. Its favorable lipophilicity enables efficient blood-brain barrier penetration, significantly enhancing antiepileptic activity. Brivaracetam demonstrates high bioavailability, rapid oral absorption, and favorable pharmacokinetic and safety profiles. Its excellent central nervous system tolerability represents a key advantage over other antiepileptic drugs.

Study Rationale： This extension study is designed to evaluate the long-term safety and sustained efficacy of adjunctive brivaracetam in Chinese patients with uncontrolled focal epilepsy who have completed the preceding QF-Brivaracetam-POS-301 trial. Eligible subjects are those who, in the investigator's judgment, may benefit from continued brivaracetam treatment, have not experienced intolerable drug-related adverse events, and are willing to continue brivaracetam therapy during the extension phase.

Inclusion criteria

• Able to understand and voluntarily sign the written informed consent form for this extension trial.
• Considered reliable by the investigator and capable of complying with the study protocol, including completing seizure diaries, attending study visits, and adhering to treatment.
• Completed the 12-week double-blind maintenance treatment period of the preceding QF-Brivaracetam-POS-301 trial.
• Judged by the investigator to be likely to benefit from long-term treatment with brivaracetam.
• Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to the first study drug administration and agree to use a medically acceptable method of contraception during the trial and for 3 months after the last dose of study drug. Male subjects with partners of childbearing potential must agree to use effective contraception during the trial and for 3 months after the last dose of study drug.

Exclusion criteria

• Known hypersensitivity to brivaracetam, levetiracetam, or other pyrrolidine derivatives; or history of multiple severe allergies.
• Any medical or psychiatric condition that, in the investigator's opinion, may jeopardize or impair the subject's ability to participate in the trial; or clinically significant abnormal laboratory values including: calculated CrCL < 30 mL/min (Cockcroft-Gault formula), platelets < 80×10^9/L, neutrophils < 1.8×10^9/L, ALT/AST/ALP > 2×ULN, or GGT > 3×ULN.
• QTc interval > 450 ms on 12-lead ECG, confirmed by repeat testing (average of 3 measurements remains > 450 ms).
• Female subjects who are pregnant or breastfeeding.
• History of suicide attempts (including actual attempts, interrupted attempts, aborted attempts, or preparatory acts/behavior) or current suicidal ideation, as assessed by the C-SSRS scale.
• Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this trial.