Phase 3
N=681
An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Adults With Dravet or Lennox-Gastaut Syndromes
Epilepsy · Dravet Syndrome · Lennox-Gastaut Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT02224573 ↗Enrolled (actual)
681
Serious AEs
42.6%
Results posted
Feb 2022
Primary outcome: Primary: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group — 306; 353; 135; 140 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- GWP42003-P (Drug)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- GW Research Ltd
- Primary completion
- Sep 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group |
306; 353; 135; 140; 63; 107 | — |
| PRIMARY 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 |
59; 88; 96; 120; 139; 176 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Body Mass Index (BMI) |
0.42; 0.05 | — |
| PRIMARY Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose |
13; 21; 62; 120; 2; 4 | — |
| PRIMARY 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 |
1; 1; 1; 2; 0; 1 | — |
| PRIMARY Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up |
9.8; 4.9; 3.4; 0.0; 2.4; 4.9 | — |
| PRIMARY 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 |
4.0; 6.0; 2.9; 2.1; 2.4; 2.0 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Red Blood Cells (RBCs) Values |
-0.068; -0.059 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hemoglobin Levels |
-1.6; -2.4 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hematocrit Values |
-0.0105; -0.0110 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Volume |
-1.0; -1.3 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Hemoglobin |
0.10; -0.15 | — |
| PRIMARY 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 |
5.4; 5.0; -0.52; -0.09; 0.00; 0.01 | — |
| PRIMARY 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) |
0.08; 0.12; -0.10; -0.24; -1.32; -1.32 | — |
| PRIMARY 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 |
-0.4; -0.8; -0.06; -0.08; -0.08; 0.00 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin |
7.0; 7.1; 3.8; 4.0; 0.48; 0.45 | — |
| PRIMARY 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) |
0.3; 0.0; 0.0; -0.6 | — |
| PRIMARY 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 |
-40.9; -40.1; 4.0; 2.8; 7.0; 9.5 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Albumin and Protein |
-0.2; -0.9; -1.2; -2.0 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prolactin |
0.43; 10.43 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin Time |
-0.08; -0.09 | — |
| PRIMARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin International Normalized Ratio |
-0.012; -0.010 | — |
| PRIMARY 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 |
-0.28; 1.10 | — |
| PRIMARY Mean Subject/Caregiver Global Impression of Change (S/CGIC) Score |
3.0; 2.8 | — |
| PRIMARY Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency |
-65.8; -58.9; -71.3; -66.4; -79.8; -65.3 | — |
| PRIMARY 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 |
-59.4; -69.4; -70.8; -68.7; -59.4 | — |
| PRIMARY 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 |
-52.9; -64.3; -69.4; -72.3; -55.6; -40.0 | — |
| PRIMARY Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) |
14; 14; 13; 7; 277; 352 | — |
| SECONDARY 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 |
3.7; 6.0 | — |
| SECONDARY 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 |
1.3 | — |
| SECONDARY 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 |
-0.4; -0.5; -0.8; -0.3; -1.1; -0.7 | — |
| SECONDARY Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit |
5; 9; 4; 9; 3; 0 | — |
| SECONDARY Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures |
108; 169; 73; 148; 48; 128 | — |
| SECONDARY 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) |
89; 101; 17; 24; 39; 132 | — |
| SECONDARY 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 |
0.00; -0.33 | — |
| SECONDARY 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 |
0.00; 0.00 | — |
| SECONDARY 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 |
0.00; 0.00 | — |
| SECONDARY 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 |
0.00; 0.00 | — |
| SECONDARY 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 |
0.00; -1.33 | — |
| SECONDARY 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) |
1.26; 9.55 | — |
| SECONDARY 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) |
1.16; 9.23 | — |
| SECONDARY 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) |
1.31; 10.21 | — |
| SECONDARY 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 |
0.00 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score |
0.0; 0.0; 0.0; 0.25; -0.14 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score |
0.0; 0.13; 0.0; -0.25; 0.14 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score |
0.00; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score |
0.0; 0.13; 0.0; 0.25; -0.14 | — |
| SECONDARY 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 |
0.00; -4.00 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WASI-II Matrix Reasoning T Score |
-1.50; -3.29 | — |
| SECONDARY 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 |
-0.40 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Backward Scaled Score |
0.00 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Forward Scaled Score |
0.57 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Backward Scaled Score |
0.00 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Forward Scaled Score |
0.17 | — |
| SECONDARY 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 |
0.0; 0.0 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Receptive Vocabulary T Score |
-1.00 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Matrix Reasoning T Score |
0.75; -19.0; -0.75 | — |
| SECONDARY 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 |
-31.00; -31.00 | — |
| SECONDARY 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 |
-1.00; 3.39 | — |
| SECONDARY Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Visual Perception Standard Scaled Score |
0.00; 2.67 | — |
Summary
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and adults with Dravet or Lennox-Gastaut syndromes.
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.
Data sourced from ClinicalTrials.gov (NCT02224573). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.