Long-term Safety and Efficacy of Adjunctive Brivaracetam in Chinese Patients With Uncontrolled Focal Epilepsy
An Open-Label, Multicenter, Long-Term Follow-Up Study to Evaluate the Safety and Sustained Efficacy of Adjunctive Brivaracetam Tablets in Chinese Patients With Uncontrolled Focal Epilepsy
This is a multicenter, open-label, single-arm, long-term follow-up trial designed to evaluate the long-term safety of adjunctive brivaracetam 200 mg/day (100 mg twice daily) in patients with partial-onset seizures. Secondary objectives include assessing the sustained efficacy of long-term brivaracetam treatment.
Subjects who completed the 12-week maintenance phase of the preceding QF-Brivaracetam-POS-301 trial (regardless of prior treatment assignment to brivaracetam or placebo) are eligible to enroll, provided they are deemed to benefit from extended treatment, have not experienced intolerable drug-related adverse events, and are willing to continue brivaracetam therapy. All enrolled patients will receive open-label brivaracetam 200 mg/day (100 mg twice daily). Dose adjustments are permitted based on seizure control and tolerability, with a maximum dose of 200 mg/day. Concomitant antiepileptic drugs (AEDs) are allowed, including dose adjustments, initiation of new AEDs, or discontinuation of existing AEDs.
The trial consists of four phases: a 1-week screening/lead-in phase, an extended treatment period, a 3-week dose tapering phase, and a 30-day safety follow-up period. During the extended treatment phase, study visits occur at Weeks 4, 12, 24, 36, and 52, followed by in-person visits every 6 months and telephone visits every 3 months thereafter. Unscheduled visits are allowed for adverse events or worsening seizure control. The dose tapering phase, which is optional, involves gradual discontinuation of brivaracetam over 3 weeks, or adjusted per the investigator's clinical judgment. The safety follow-up phase occurs 30 days after the last dose of study drug.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Shanghai Municipality
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Shanghai、Shanghai Municipality、中国、200040
- Huashan Hospital, Fudan University
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Brivaracetam Extended Treatment Arm
All enrolled subjects receive open-label brivaracetam tablets as extended treatment.
The initial dose is 200 mg/day (100 mg twice daily, oral administration).
Dose adjustments are allowed based on seizure control and tolerability, with a maximum dose not exceeding 200 mg/day.
Concomitant antiepileptic drugs are permitted, including dose adjustments, initiation of new AEDs, or discontinuation of existing AEDs.
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Brivaracetam tablets, oral administration, initial dose 200 mg/day (100 mg twice daily).
Dose adjustments are allowed based on clinical response and tolerability, with a maximum dose not exceeding 200 mg/day.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Treatment Emergent Adverse Event (TEAE) Incidence Rate
時間枠：baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Proportion of subjects with at least one treatment-emergent adverse event (TEAE) during
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baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Subject Discontinuation Rate Due to Adverse Events (AEs)
時間枠：baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Proportion of subjects who permanently discontinue study treatment due to an adverse event
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baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Serious Adverse Event (SAE) Incidence Rate
時間枠：baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Proportion of subjects who experience at least one serious adverse event (SAE) during the extended treatment period
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baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Partial-Onset Seizure (POS, Type 1) Frequency per 28 Days
時間枠：baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Partial-onset seizure frequency per 28 days, calculated as (total number of partial-onset seizures) / (number of non-missing seizure diary days during treatment) × 28.
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baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Change in Partial-Onset Seizure (POS, Type 1) Frequency per 28 Days
時間枠：baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Change from baseline in partial-onset seizure frequency per 28 days, calculated as (baseline value - value at each assessment window) / baseline value × 100%
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baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Responder Rates (50%, 75%, 90%) for Partial-Onset Seizure (POS, Type 1) Frequency
時間枠：baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
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Proportion of subjects with ≥50%, ≥75%, and ≥90% reduction in partial-onset seizure frequency compared to the baseline period of the preceding QF-Brivaracetam-POS-301 trial
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baseline,Weeks 4, 12, 24, 36, 52, and up to 2years
|
協力者と研究者
捜査官
- 主任研究者：Zhen Hong, MD、Huashan Hospital
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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