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
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 主要终点
- Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
To evaluate the safety and pharmacokinetics (PK) of multiple doses of GWP42003-P compared with placebo in children with Dravet syndrome.
详细描述
This multi-center study consisted of 2 parts: Part A and Part B. Only Part A is described in this record. Part A was a randomized, double-blind 21-day treatment study period. Participants were randomized to one of 3 doses of active drug or placebo at a 4:1 ratio.
Participants who satisfied all inclusion and none of the exclusion criteria were assigned a unique participant number and then began a 28-day baseline observation period.
Eligible participants were then randomly assigned to receive one of 3 dose levels of GWP42003-P: 5 milligrams (mg) per kilogram (kg) per day, 10 mg/kg/day, 20 mg/kg/day, or matching placebo.
There were three groups of ten participants. In each group, participants were randomly assigned so that eight participants received active treatment and two participants received placebo. Participants received GWP42003-P or placebo for a 21-day exposure period, which consisted of a titration period, followed by a stable dose period.
A PK assessment took place after the first single dose of GWP42003-P. There was a second PK assessment after 21 days of consecutive dosing with GWP42003-P. Participants who took clobazam (CLB) as an adjunctive treatment were asked to take their usual dose 2 hours prior to attending the clinic. The same recommendation was made for other concomitant antiepileptic drugs (AEDs), if applicable. This was so that the pre-treatment (with GWP42003-P) plasma concentrations of CLB, its major metabolite N-desmethylclobazam, and any other concomitant AEDs could be measured, and the impact of GWP42003-P treatment on these levels evaluated. Interim clinic visits to (primarily) evaluate safety and adherence to the titration regimen took place at 7 and 14 days of treatment.
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
- 4 Years 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants were male or female aged between 4 and 10 years (inclusive).
- •Participants had a documented history of Dravet Syndrome that was not completely controlled by AEDs.
- •Participants took one or more AEDs at a dose which had been stable for at least 4 weeks.
- •Participants had experienced fewer than 4 convulsive seizures (tonic-clonic, tonic, clonic, atonic seizures) during the 28-day baseline period.
- •All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation [VNS]) were stable for four weeks prior to screening and participants were willing to maintain a stable regimen throughout the study. The ketogenic diet and VNS treatments were not counted as an AED.
排除标准
- •Participants had clinically significant unstable medical conditions other than epilepsy.
- •Participants had clinically relevant abnormalities in the 12-lead electrocardiogram measured at screening or randomization.
- •Participants were currently using or had in the past used recreational or medicinal cannabis, or synthetic CBD based medications (including Sativex®) within the 3 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 IMP.
- •Participants who had been part of a clinical trial involving another investigational product in the previous 6 months.
- •There were plans for the participants to travel outside their country of residence during the study.
- •Participants were previously randomized into this study. In particular, participants participating in Part A of the study cannot enter Part B.
研究组 & 干预措施
GWP42003-P 5 mg/kg/day Dose
Participants received GWP42003-P 5 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 5 mg/kg/day over 3 days and remained at this dose for the rest of the 21-day treatment period (19 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.
干预措施: GWP42003-P 5 mg/kg/day Dose (Drug)
GWP42003-P 10 mg/kg/day Dose
Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the rest of the 21-day treatment period (15 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.
干预措施: GWP42003-P 10 mg/kg/day Dose (Drug)
GWP42003-P 20 mg/kg/day Dose
Participants received GWP42003-P 20 mg/kg/day 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 rest of the 21-day treatment period (11 days). The 21-day treatment 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 one of the 3 dose levels (5, 10, or 20 mg/kg/day), administered orally, half in the morning and half in the evening for 21 days. To maintain the blinded aspect of the study, participants titrated the placebo dose over 3 to 11 days according to the matched investigational medicinal product (IMP) group (3, 7, and 11 days for the 5, 10, or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the rest of the 21-day treatment period. The 21-day treatment 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
Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)
时间窗: Baseline (Day 1) through Safety follow-up visit (Day 60)
A TEAE was defined as an adverse event (AE) with an onset date on or after the first dose of IMP. If an AE had a partial onset date and it was unclear from the partial date (or the stop date) whether the AE started prior to or following the first dose of IMP then the AE was considered a TEAE. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through the Safety Follow-up Visit (Day 60) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Adverse Events module.
次要结局
- Mean Percentage Change From Baseline To End Of Treatment In Plasma Clobazam (CLB) And N-Desmethylclobazam (N-CLB) Concentrations(Predose on Days 1 and 22)
- Area Under The Concentration-Time Curve Calculated To The Last Observable Concentration At Time T (AUC0-t) For CBD And Its Metabolites At Days 1 And 22(Predose and 2-6 hours postdose on Days 1 and 22)