A Double Blind, Placebo Controlled Two-part Study to Investigate the Dose-ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 120
- 主要终点
- Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period
研究概览
简要总结
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.
详细描述
GWEP1332 Part B recruited an entirely new group of participants than GWEP1332 Part A. Participants who failed the entry criteria for Part A were eligible to take part in Part B.
Part B was a 1:1 randomized, double-blind, placebo-controlled, 14-week comparison of GWP42003-P versus placebo. The aim of Part B was to assess the antiepileptic efficacy of GWP42003-P as an adjunctive antiepileptic treatment compared with placebo, with respect to the percentage change from baseline during the treatment period of the study in convulsive seizure frequency in children and young adults.
Following the establishment of initial eligibility and baseline measurements, participants entered Part B and began a 28-day baseline observation period.
Eligible participants were then randomized to receive either GWP42003-P or placebo on a 1:1 basis and titrated up to the target dose that was identified in Part A (up to 20 milligrams [mg] per kilogram [kg] per day), which was confirmed following completion of Part A by an independent Data Safety Monitoring Committee who reviewed unblinded safety and pharmacokinetic data from Part A.
Participants received investigational medicinal product for 14 weeks, consisting of a titration period followed by a 12-week maintenance period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants were male or female aged between 2 and 18 years (inclusive).
- •Participants had a documented history of Dravet Syndrome that was not completely controlled by current antiepileptic drugs.
- •Participants took one or more antiepileptic drugs at a dose that had been stable for at least four weeks.
- •All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation) were stable for four weeks prior to screening and participants were willing to maintain a stable regimen throughout the study.
排除标准
- •Participants had clinically significant unstable medical conditions other than epilepsy.
- •Participants had clinically relevant symptoms or a clinically significant illness in the four weeks prior to screening or randomization, other than epilepsy.
- •Participants were currently using or had in the past used recreational or medicinal cannabis or synthetic cannabinoid based medications (including Sativex®) within the three months prior to study entry and were unwilling to abstain for the duration for the study.
- •Participants had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
- •Participants had been part of a previous clinical trial involving another investigational product in the previous six months.
- •There were plans for the participants to travel outside their country of residence during the study.
- •Participants previously randomized into this study. In particular, participants who participated in Part A of the study could not enter Part B.
研究组 & 干预措施
GWP42003-P 20 mg/kg/day Dose
Participants received 20 mg/kg/day of GWP42003-P administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
干预措施: GWP42003-P 20 mg/kg/day Dose (Drug)
Placebo
Participants received placebo (0 mg/mL CBD), volume-matched to the 20 mg/kg/day dose level, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day of the matched dose) period.
干预措施: Placebo control (Drug)
结局指标
主要结局
Percentage Change From Baseline In Convulsive Seizure Frequency During The Treatment Period
时间窗: Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)
Convulsive seizures (atonic, clonic, tonic, or tonic-clonic) were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Percentage change from baseline was calculated as: (\[frequency during the treatment period - frequency during baseline\]/frequency during baseline) \* 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) \* 28. Baseline included all available data prior to Day 1 (28-day average). Negative percentages show an improvement from baseline.
次要结局
- Number Of Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period(Baseline to EOT (Day 99) or ET)
- Change From Baseline In Epworth Sleepiness Scale (ESS) Score(Baseline to Last Visit (Day 99) or ET)
- Caregiver Global Impression Of Change (CGIC)(Baseline to Last Visit (Day 99) or ET)
- Number Of Participants Using Rescue Medication(Baseline to EOT (Day 99) or ET)
- Change From Baseline In Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Score(Baseline to Last Visit (Day 99) or ET)
- Number of Participants With A ≥25%, ≥75% Or 100% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period(Baseline to EOT (Day 99) or ET)
- Number Of Participants With Inpatient Hospitalizations Due To Epilepsy(Baseline to Safety Follow-up (Day 137))
- Caregiver Global Impression Of Change In Seizure Duration (CGICSD)(Baseline to EOT (Day 99) or ET)
- Percentage Change From Baseline In Non-Convulsive Seizure Frequency During The Treatment Period(Baseline to EOT (Day 99) or ET)
- Change From Baseline In Sleep Disruption 0 To 10 Numerical Rating Scale (0 to 10 NRS) Score(Baseline to Last Visit (Day 99) or ET)
- Change From Baseline In Quality Of Life In Childhood Epilepsy (QOLCE) Score(Baseline to EOT (Day 99) or ET)