Clinical trial NCT02224573: An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Adults With Dravet or Lennox-Gastaut Syndromes
Official title: An Open Label Extension Study to Investigate the Safety of Cannabidiol (GWP42003-P; CBD) in Children and Adults With Inadequately Controlled Dravet or Lennox-Gastaut Syndromes.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Dravet Syndrome
Lennox-Gastaut Syndrome
Keywords: Cannabidiol
CBD
GWP42003-P
GWPCARE5
Lead sponsor: GWResearch
Sponsor class: UNKNOWN
First posted: 2014-08-25
Enrollment: 681
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and adults with Dravet or Lennox-Gastaut syndromes.

Detailed description: This is a multi-center, open-label extension study for participants with Dravet syndrome or Lennox-Gastaut syndrome who have previously participated in double-blind, placebo-controlled clinical studies of GWP42003-P (Core Studies: GWEP1332A \[NCT02091206\], GWEP1332B \[NCT02091375\], GWEP1424 \[NCT02224703\], GWEP1414 \[NCT02224560\], GWEP1424 \[NCT02224703\], and GWEP1423 \[NCT02224690\]). The first participant was enrolled into the open-label extension study after the Data Safety Monitoring Committee reviewed the safety data from Part A of study GWEP1332.

Eligibility criteria: Key Inclusion Criteria:

• Participant has completed the treatment phase of their Core Studies: GWEP1332A \[NCT02091206\], GWEP1332B \[NCT02091375\], GWEP1424 \[NCT02224703\], GWEP1414 \[NCT02224560\], GWEP1424 \[NCT02224703\], and GWEP1423 \[NCT02224690\].

Key Exclusion Criteria:

* Participant is 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 other than the investigational medicinal product (IMP) received during the Core Study and are unwilling to abstain for the duration for the study.
* Any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Visit 1.
* Participant has been part of a clinical trial involving an IMP during the inter-study period.
* Female participant is of child bearing potential or male participant's partner is of child bearing potential, unless willing to ensure that they or their partner use highly effective contraception, for example, hormonal contraceptives, intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence, during the study and for 3 months thereafter (however, a male condom should not be used in conjunction with a female condom).
* Participant has significantly impaired hepatic function at the 'End of Treatment' visit of their Core Study or at Visit 1 if re-assessed: i) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>5 × upper limit of normal (ULN); ii) ALT or AST \>3 × ULN and (total bilirubin \[TBL\] \>2 × ULN or international normalized ratio \[INR\] \>1.5); iii) ALT or AST \>3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (\>5%). This criterion must be confirmed prior to entering the study.

Primary outcomes:
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group
timeFrame: up to Week 260
measure: Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Body Mass Index (BMI)
timeFrame: up to Week 260
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose
timeFrame: up to Week 260
measure: Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose
timeFrame: up to Week 260
measure: Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up
timeFrame: up to Week 260
measure: Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Red Blood Cells (RBCs) Values
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hemoglobin Levels
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hematocrit Values
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Volume
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Hemoglobin
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs)
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol
timeFrame: up to week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine Clearance (Schwartz) and Creatinine Clearance (Cockcroft-Gault)
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Albumin and Protein
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prolactin
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin Time
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin International Normalized Ratio
timeFrame: up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Insulin-like Growth Factor-1 (IGF-1) Levels
timeFrame: up to Week 260
measure: Mean Subject/Caregiver Global Impression of Change (S/CGIC) Score
timeFrame: Baseline; up to Week 260
measure: Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency
timeFrame: Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks
measure: Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Drop Seizure Frequency in Participants With Lennox-Gastaut Syndrome
timeFrame: Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, and Last 12 Weeks
measure: Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome
timeFrame: Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks
measure: Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus)
timeFrame: Baseline; At last 12 weeks
Secondary outcomes:
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Quality of Life in Childhood Epilepsy (QOLCE) Scores
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment QOL in Epilepsy Scores (QOLIE-31-P) in Participants With Lennox-Gastaut Syndrome
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores
timeFrame: Baseline; up to Week 260
measure: Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit
timeFrame: Week 48, 104, 156, 208, and End of Treatment (up to Week 260 based on when the participant discontinued treatment)
measure: Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures
timeFrame: Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks
measure: Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD)
timeFrame: Up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Delis-Kaplan Executive Function System (D-KEFS) Visual Scanning Completion Time Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number Sequencing Completion Time Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Letter Sequencing Completion Time Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number-letter Switching Completion Time Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Motor Speed Completion Time Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Both Hands Z Score)
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Dominant Hand Z Score)
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Non Dominant Hand Z Score)
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Adult Intelligence Scale (WAIS) Coding Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Abbreviated Scale of Intelligence (WASI)-II Vocabulary T Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WASI-II Matrix Reasoning T Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Intelligence Scale for Children (WISC) Coding Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Backward Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Forward Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Backward Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Forward Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Preschool & Primary Scale of Intelligence (WPPSI)-IV Bug Search T Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Receptive Vocabulary T Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Matrix Reasoning T Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Expressive One-Word Picture Vocabulary Test (EOWPVT) Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in a Developmental NEuroPSYchological Assessment (NEPSY)-2 Word Generation Scaled Score
timeFrame: Baseline; up to Week 260
measure: Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Visual Perception Standard Scaled Score
timeFrame: Baseline; up to Week 260
Other outcomes:
Locations:
Study officials:
References:
citation: Scheffer IE, Halford JJ, Miller I, Nabbout R, Sanchez-Carpintero R, Shiloh-Malawsky Y, Wong M, Zolnowska M, Checketts D, Dunayevich E, Devinsky O. Add-on cannabidiol in patients with Dravet syndrome: Results of a long-term open-label extension trial. Epilepsia. 2021 Oct;62(10):2505-2517. doi: 10.1111/epi.17036. Epub 2021 Aug 18.
citation: Patel AD, Mazurkiewicz-Beldzinska M, Chin RF, Gil-Nagel A, Gunning B, Halford JJ, Mitchell W, Scott Perry M, Thiele EA, Weinstock A, Dunayevich E, Checketts D, Devinsky O. Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trial. Epilepsia. 2021 Sep;62(9):2228-2239. doi: 10.1111/epi.17000. Epub 2021 Jul 20.