A Phase 2, Open-label, Dose-finding Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Pharmaceutical Grade Synthetic Cannabidiol Oral Solution in Pediatric Patients With Treatment-Resistant Childhood Absence Seizures
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 11
- 主要终点
- Percent Change From Baseline in Absence Seizure Counts Assessed by Video-electroencephalogram (EEG) at Visit 5
研究概览
简要总结
The primary purpose of this study is to assess the efficacy of Cannabidiol Oral Solution in the treatment of pediatric participants with treatment-resistant childhood absence seizures. This study will also assess safety, tolerability and pharmacokinetics of Cannabidiol Oral Solution, and any improvement in qualitative assessments of participant status over the duration of the study in pediatric participants with treatment-resistant childhood absence seizures. The study will include a 4-week Screening Period, a 5 or 10 day Titration Period (depending study Cohort), a 4-week Treatment Period followed by 5-day Tapering for doses >20 mg/kg/day and a 4-week Follow-up Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient and/or parent(s)/caregiver(s) fully comprehend the informed consent form and assent form, understand all study procedures, and can communicate satisfactorily with the investigator and study coordinator, in accordance with applicable laws, regulations, and local requirements.
- •Male or female between 3 and 12 years (inclusive) at the time of onset and between 3 and 17 years of age (inclusive) at the time of consent.
- •Body weight ≥ 10 kg.
- •Diagnosed with childhood absence epilepsy, confirmed by electroencephalogram (EEG) with at least 3 bursts of general spike wave of 2.7 to 5 hertz lasting ≥3 seconds during the 4-hour EEG, and has had an adequate trial of at least 2 antiepileptic drugs (AEDs) and are treatment-resistant to at least one AED.
- •Willingness to not start a ketogenic diet during the Baseline or Treatment Period.
- •A female patient is eligible to participate in the study if she is premenarchal, or of childbearing potential with a negative urine pregnancy test at the Screening Visit. If sexually active, she must agree to either complete abstinence from intercourse or use acceptable methods of contraception throughout the study and for 4 weeks after completion of study participation or discontinuation from investigational product.
- •A sexually active male patient must be willing to use acceptable methods of contraception throughout the study and for 4 weeks after completion of study participation or discontinuation from investigational product.
- •In the opinion of the investigator, the parent(s)/caregiver(s) is willing and able to comply with the study procedures and visit schedules and the Follow-up Visits.
- •General good health based on physical and neurological examinations, medical history, and clinical laboratory values completed during the Screening Visit that would prohibit the patient from safely participating in the trial as judged by the investigator.
排除标准
- •Patient or parent(s)/caregiver(s) have daily commitments during the study duration that would interfere with attending all study visits.
- •Has a history of nonfebrile seizures other than absence seizures.
- •Has a history of febrile seizures after 3 years of age.
- •Has a history consistent with juvenile absence epilepsy or juvenile myoclonic epilepsy.
- •Currently taking felbamate.
- •Currently taking phenytoin, fluvoxamine, carbamazepine, or St. John's Wort.
- •Currently taking concomitant medications that are strong inhibitors/inducers/sensitive substrates with a narrow therapeutic index for cytochrome P450 3A4 (CYP3A4), CYP2C9, or CYP2C
- •(Stable doses of Valproic Acid during the screening, titration, treatment, and follow-up periods are permitted).
- •Currently on a ketogenic diet.
- •In the opinion of the investigator, any clinically significant, unstable medical abnormality, chronic disease, or a history of a clinically significant abnormality of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems.
- •Clinically significant abnormal liver function test (LFT) values, including albumin, direct bilirubin, total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≥3 times the upper limit of normal (ULN).
- •History or presence of abnormal electrocardiograms (ECGs) that are clinically significant in the opinion of the investigator.
- •Has a current or history of clinically significant intellectual disability or major psychiatric disease, including autism spectrum disorder, which would interfere with compliance.
- •For patients aged 7 to 17 years of age and for whom the Columbia Suicide Severity Rating Scale (C-SSRS) is developmentally appropriate, an affirmative answer to queries regarding active suicidal ideation with some intent to act but without a specific plan or active suicidal ideation with a specific plan and intent on the C-SSRS assessment at the Screening Visit.
- •Any history of attempted suicide.
- •Previously received any investigational drug or device or investigational therapy within 30 days before Screening.
- •Taken any cannabinoids in the 30 days prior to the Screening Visit.
- •History of an allergic reaction or a known or suspected sensitivity to any substance that is contained in the investigational product formulation.
- •Known infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- •In the opinion of the investigator, the patient is unsuitable in any other way to participate in this study.
- •Body weight <10 kg or >90 kg.
研究组 & 干预措施
Cohort 1: Cannabidiol Oral Solution 20 mg/kg/day
Treatment Period: Cannabidiol Oral Solution 20 milligrams per kilogram per day (mg/kg/day) divided twice daily (BID) for 4 weeks.
干预措施: Cannabidiol Oral Solution (Drug)
Cohort 2: Cannabidiol Oral Solution 30 mg/kg/day
Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days.
Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks.
干预措施: Cannabidiol Oral Solution (Drug)
Cohort 3: Cannabidiol Oral Solution 10 mg/kg/day
Treatment Period: Cannabidiol Oral Solution 10 mg/kg/day divided BID for 4 weeks.
干预措施: Cannabidiol Oral Solution (Drug)
结局指标
主要结局
Percent Change From Baseline in Absence Seizure Counts Assessed by Video-electroencephalogram (EEG) at Visit 5
时间窗: Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period)
A 4-hour video-EEG was performed for all participants at Baseline, during the Treatment Period, and at the End of the Study/Early Withdrawal Visit. Hyperventilation was conducted during the video-EEG to count the number of absence seizures. A negative change value indicates an improvement in seizure activity. A positive change value indicates a worsening in seizure activity. Percent change from baseline was calculated as (100\*(week 4-baseline)/baseline).
Percent Change From Baseline in Time to Absence Seizure During Hyperventilation Testing on Video-EEG at Visit 5
时间窗: Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period)
A 4-hour video-EEG was performed for all participants at Baseline, during the Treatment Period, and at the End of the Study/Early Withdrawal Visit. Hyperventilation was conducted during the video-EEG to count the number of absence seizures. Percent change from baseline calculated as (100\*(week 4-baseline)/baseline).
Number of Participants Seizure-Free at Visit 5
时间窗: Visit 5 (Week 4, Day 6 of Treatment Period)
Daily seizure activity was recorded in a diary. Each day, the participant or parent/caregiver responded to the question: "How many absence seizures did the patient have today?".
Clinical Global Impression of Improvement (CGI-I) Score at Visit 5
时间窗: Visit 5 (Week 4, Day 6 of Treatment Period)
The CGI-I questionnaire was completed by the parents/caregivers and the investigator and was used to assess participants' global status of their condition at Week 4 of the Treatment Period using a 7-point scale, where 1=very much improved and 7=very much worse since the initiation of treatment.
次要结局
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 (after dosing) up to Visit 7 (Week 4 of the Follow-Up Period))
- Maximum Plasma Concentration (Cmax) and Dose-normalized Cmax (Cmax/D) for Cannabidiol Under Fed and Fasted Conditions(Visit 3 (Week 1, Day 1 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), Visit 5 (Week 4, Day 6 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), and Visit 6 (Week 4, Day 7 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose))
- Area Under the Plasma Concentration Curve From Time 0 to the Last Measured Concentration (AUC(0-t)) and Dose Normalized AUC(0-t) [AUC(0-t)/Dose] for Cannabidiol Under Fed and Fasted Conditions(Visit 3 (Week 1, Day 1 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), Visit 5 (Week 4, Day 6 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), and Visit 6 (Week 4, Day 7 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose))
- Trough Plasma Concentration (Ctrough) and Dose Normalized Ctrough (Ctrough/Dose) for Cannabidiol Under Fed, Fasted, and Normal Conditions(Visit 3 (Week 1, Day 1 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), Visit 5 (Week 4, Day 6 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), and Visit 6 (Week 4, Day 7 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose))