Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1)

Jazz Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Epilepsy; Dravet Syndrome

Treatments: Drug: Placebo control; Drug: GWP42003-P 20 mg/kg/day Dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT02091375

GWEP1332 Part B

2014-002941-23 (EudraCT Number)

Details and patient eligibility

About

To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.

Full description

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.

Efficacy and safety were monitored at various clinic visits and via telephone. After 14 weeks of treatment, all participants were offered the option of entering an open label extension (OLE) study. Entry was within seven days of the final treatment visit. Participants who did not immediately enter the OLE study commenced a down-titration taper period lasting up to 10 days. The taper period was interrupted if the participant wished to enter the open label extension study within the seven-day timeframe.

For participants who opted not to enter the OLE study, a follow-up telephone call was made 28 days after the end of dosing and weekly safety telephone calls were made during the 28-day follow-up period.

Enrollment: 120 patients

Sex: All

Ages: 2 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

120 participants in 2 patient groups, including a placebo group

GWP42003-P 20 mg/kg/day Dose

Experimental group

Description:

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.

Treatment:

Drug: GWP42003-P 20 mg/kg/day Dose

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo control