Clinical trial NCT02224690: A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults
Official title: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Lennox-Gastaut Syndrome
Keywords: Cannabidiol
CBD
Epidiolex
GWP42003-P
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-08-25
Enrollment: 171
Sex: ALL
Minimum age (years): 2
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of GWP42003-P as adjunctive treatment in reducing the number of drop seizures when compared with placebo, in participants with Lennox-Gastaut Syndrome (LGS).

Detailed description: This study was a 1:1 randomized, double-blind, 14-week comparison of 20 milligram \[mg\] per kilogram \[kg\] per day \[mg/kg/day\] of GWP42003-P versus placebo. The treatment period consisted of a 2-week titration period followed by a 12-week maintenance period. The study determined the efficacy, safety and tolerability of GWP42003-P compared with placebo. The dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332. The first participants enrolled into this study after the DSMC reviewed the safety data from Part A of study GWEP1332. Following study completion, all participants were invited to continue to receive GWP42003-P in an open label extension (OLE) study (under a separate protocol).

Eligibility criteria: Key Inclusion Criteria:

* Participant must have been male or female aged between 2 and 55 years (inclusive).
* Participant must have had a documented history of Lennox-Gastaut syndrome. This included written documentation of having met electroencephalogram (EEG) diagnostic criteria during the participant's history and evidence of at least 1 type of generalized seizure, including drop seizures (atonic, tonic, tonic-clonic or myoclonic) for at least 6 months.
* Participants had a history of slow (\<3.0 Hertz) spike-and-wave pattern in an EEG prior to the enrollment into the baseline period.
* Participants were refractory; that is having documented failures on more than one antiepileptic drug (AED).
* Participant must have been taking 1 or more AEDs at a dose which has been stable for at least 4 weeks prior to screening.
* All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation \[VNS\]) must have been stable for 4 weeks prior to screening and participant is willing to maintain a stable regimen throughout the study. The ketogenic diet and VNS treatments are not accounted as an AED.

Key Exclusion Criteria:

* Etiology of participant's seizures was a progressive neurologic disease. Participants with tuberous sclerosis were not excluded from study participation, unless there was a progressive tumor.
* Participant had an anoxic episode requiring resuscitation within 6 months of screening.
* Participant had clinically significant unstable medical conditions other than epilepsy.
* Participant had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or randomization, other than epilepsy.
* Participant was currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex®) within the 3 months prior to study entry and was unwilling to abstain for the duration of the study.
* Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), such as sesame oil.
* Participant had been part of a clinical trial involving another IMP in the previous 6 months.
* Participant had significantly impaired hepatic function at screening or randomization (Alanine aminotransferase \[ALT\] \>5 x upper limit of normal \[ULN\] or total bilirubin \[TBL\] \>2 x ULN) OR the ALT or Aspartate aminotransferase (AST) \>3 x ULN and (TBL \>2 x ULN or international normalized ratio \>1.5). This criterion can only be confirmed once the laboratory results are available; Participants randomized into the study who are later found not to meet this criterion should be withdrawn from the study.
* Any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale in the last month or at screening.
* Participant was taking more than 4 concurrent AEDs.
* Participant was taking corticotropins in the 6 months prior to screening.
* Participant was taking long-term systemic steroids (excluding inhaled medication for asthma treatment) or any other daily medication known to exacerbate epilepsy. An exception was made of prophylactic medication, for example, idiopathic nephrotic syndrome or asthma.
* Participant was taking felbamate, and they had been taking it for less than 1 year prior to screening.

Primary outcomes:
measure: Percentage Change From Baseline In Drop Seizure Frequency During The Treatment Period
timeFrame: Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)
Secondary outcomes:
measure: Number Of Participants With a ≥50% Reduction From Baseline in Drop Seizure Frequency During The Treatment Period
timeFrame: Baseline to EOT (Day 99) or ET
measure: Percentage Change From Baseline In Total Seizure Frequency During The Treatment Period
timeFrame: Baseline to EOT (Day 99) or ET
measure: Subject/Caregiver Global Impression Of Change Assessment (S/CGIC)
timeFrame: Baseline to Last Visit (Day 99) or ET
Other outcomes:
Locations:
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Ames
country: United States
state: Iowa
city: Iowa City
country: United States
state: Iowa
city: Lexington
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Saint Paul
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Lebanon
country: United States
state: New Hampshire
city: Bronx
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Winchester
country: United States
state: Virginia
city: Denekamp
country: Netherlands
state: BV Zwolle
city: Bydgoszcz
country: Poland
city: Gdańsk
country: Poland
city: Kraków
country: Poland
city: Lublin
country: Poland
city: Lublin
country: Poland
city: Poznań
country: Poland
Study officials:
References:
citation: Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17;391(10125):1085-1096. doi: 10.1016/S0140-6736(18)30136-3. Epub 2018 Jan 26.
citation: Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4.
citation: Privitera M, Bhathal H, Wong M, Cross JH, Wirrell E, Marsh ED, Mazurkiewicz-Beldzinska M, Villanueva V, Checketts D, Knappertz V, VanLandingham K. Time to onset of cannabidiol (CBD) treatment effect in Lennox-Gastaut syndrome: Analysis from two randomized controlled trials. Epilepsia. 2021 May;62(5):1130-1140. doi: 10.1111/epi.16878. Epub 2021 Apr 2.