A 57-Week, Multicenter, Active-treatment, Open-label Extension Trial of CVL-865 as Adjunctive Therapy in Adults With Drug-Resistant Focal Onset Seizures
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 105
- 试验地点
- 54
- 主要终点
- Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
The purpose of this study is to assess the long-term safety and tolerability of CVL-865 as adjunctive therapy in participants with focal onset seizures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who completed treatment in Trial CVL-865-SZ-001 (NCT04244175)
- •A female participant of childbearing potential who is sexually active with a nonsterilized male partner must agree to use a highly effective method of contraception from signing of informed consent through 30 days post last dose
- •A male participant with a pregnant or a nonpregnant partner of childbearing potential must agree to use a condom during treatment and until the end of relevant systemic exposure in the male participant for 94 days following the last dose with the investigational medicinal product (IMP)
- •Participants who are capable of giving signed informed consent
- •Participants who are able, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures
排除标准
- •Participants who, in the opinion of the investigator, medical monitor, or sponsor, should not participate in the trial
- •Participants who, in the judgment of the investigator, experienced poor tolerability to the IMP during the double-blind trial or whose safety assessments resulted in new concerns that would suggest that the participant may not be appropriate for 57 weeks of treatment with CVL-865 in an extension trial
- •Participants who experienced status epilepticus during Trial CVL-865-SZ-001
- •Participants who have demonstrated substantial noncompliance to trial procedures in Trial CVL-865-SZ-001, based on the investigator's judgment, would not be eligible for this trial
- •Participants who answer "yes" on the C-SSRS Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent), or participants who answer "yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior), or participants who, in the opinion of the investigator, present a serious risk of suicide
- •Participants with any of the following abnormalities in clinical laboratory tests at Visit 1, as assessed by the central laboratory and confirmed by a single repeat measurement, if deemed necessary (Females: Hemoglobin <11 gram per deciliter (g/dL); Males: hemoglobin <12 g/dL; White blood cell (WBC) count <3.0 x 10 power 9 per liter (10^9/L); Neutrophil count <2.0 x 10^9/L; Platelet count <150 × 10^9/L)
- •Participants who would be likely to require the use of prohibited concomitant medications during the trial
- •Female participants who have a positive pregnancy test result
研究组 & 干预措施
CVL-865 25 mg
Participants will receive CVL-865 tablets orally twice daily (BID) up to the maximum dose of 25 milligrams (mg) until Week 57 during the treatment period.
干预措施: CVL-865 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: From first dose of study drug up to Week 61
A TEAE was defined as an AE that started after the first dose of IMP in the open-label trial or a previously reported AE that increased in intensity, became serious, trial drug-related, or resulted in death, discontinuation, interruption, of reduction of IMP after the first dose of IMP in the open-label trial. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in the 'Reported Adverse Events module'.
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECGs)
时间窗: Baseline up to Week 57
12-lead ECGs recordings were obtained after the participant had been supine and at rest for at least 5 minutes. The number of participants with significant abnormalities is reported by 'change from baseline in QT interval as corrected for heart rate by Fridericia's formula (QTcF)'.
Number of Participants With Clinically Significant Changes From Baseline in Vital Sign Measurements
时间窗: Baseline up to Week 57
Vital signs were measured with the participant in a sitting/semi-recumbent position after 5 minutes rest and included temperature, systolic and diastolic blood pressure, and heart rate.
Number of Participants With Clinically Significant Changes From Baseline in Physical and Neurological Examination Results
时间窗: Baseline up to Week 57
A complete physical examination consisted of measurement of weight and a review of the following body systems: head, ears, eyes, nose, mouth, skin, heart, lungs, lymph nodes, and gastrointestinal, genitourinary, and musculoskeletal systems. A full neurological examination included an assessment of the participant's mental status (level of consciousness, orientation, speech, memory, etc), cranial nerves, motor (muscle appearance, tone, strength, and reflexes), sensation (including Romberg sign), coordination, and gait. Reported here is the number of participants with clinically significant changes in physical or neurological examination results.
Suicidality Based on the Columbia Suicide-Severity Rating Scale (C-SSRS)
时间窗: Baseline up to Week 61
The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).
Change From End of Treatment in Modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B) Score at the End of Post-treatment Follow-up (Week 61)
时间窗: Week 57, Week 61
The modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B) is a sensitive instrument to measure withdrawal under conditions where there is a taper of medication (rather than abrupt discontinuation). It consists of 17-items that monitor the type and severity of benzodiazepine withdrawal symptoms such as irritability, fatigue, appetite, and sleeplessness. The total score ranges from 1 (no withdrawal) to 68 (extreme withdrawal) with higher scores indicating more severe withdrawal.
次要结局
未报告次要终点