A Phase 3 interventional study of GWP42003-P and Placebo Control in Epilepsy and Dravet Syndrome, sponsored by Jazz Pharmaceuticals. Completed at 38 sites in 6 countries. Open to participants aged 2 Years to 18 Years. Per ClinicalTrials.gov, last updated 2022-09-28.
Sponsored by Jazz Pharmaceuticals · Phase 3, Interventional, and Treatment
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and young adults with Dravet syndrome.
This study was a 2:2:1:1 randomized, double-blind, 14-week comparison of two dose levels of GWP42003-P (10 milligram/kilogram [mg/kg]/day and 20 mg/kg/day) versus placebo (10 mg/kg/day dose-volume equivalent and 20 mg/kg/day dose-volume equivalent; presented as pooled placebo in the study). A 28-day screening period prior to randomization (to establish baseline parameters) preceded the treatment period, which consisted of a 2-week titration period followed by a 12-week maintenance period. The study aimed to determine the efficacy, safety, and tolerability of GWP42003-P compared with placebo. 20 mg/kg/day was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206). The first participant did not enroll into this study until the DSMC reviewed the safety data from Part A of study GWEP1332 (NCT02091206).
Following study completion, all participants were invited to continue to receive GWP42003-P in a separate open-label extension study (GWEP1415; NCT02224573).
1,842 studies on the registry are indexed under Epilepsy; 423 are open to participants now.
This study's enrollment of 199 is above the median of 50 across 1,228 interventional studies indexed under Epilepsy.
Browse Epilepsy studies →Jazz Pharmaceuticals is the lead sponsor of 173 studies on the registry; 19 are open to participants now.
Of its 42 completed or terminated interventional studies of FDA-regulated products, 31 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
GWP42003-P oral solution (100 mg/milliliter \[mL\] cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 10 mg/kg/day dose was defined as 50% of the 20 mg/kg/day dose.
Drug: GWP42003-P
GWP42003-P oral solution (100 mg/mL cannabidiol in sesame oil with anhydrous ethanol with added sweetener \[sucralose\] and strawberry flavoring). The 20 mg/kg/day dose was recommended by the DSMC after assessment of safety and pharmacokinetic data from Part A of study GWEP1332 (NCT02091206).
Drug: GWP42003-P
Excipients only. Participants were pooled from 2 placebo cohorts, half receiving 10 mg/kg/day dose-volume equivalent and half receiving 20 mg/kg/day dose-volume equivalent.
Drug: Placebo Control
Also known as: Cannabidiol, CBD, Epidiolex
Also known as: Placebo
Change In Convulsive Seizures During The Treatment Period Compared To Baseline
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.
Time frame: Baseline to Day 99 or Early Termination (ET)
Change In Total Seizures During The Treatment Period Compared To Baseline
Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.
Time frame: Baseline to Day 99 or ET
Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: (\[frequency during the treatment period - frequency during baseline\]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).
Time frame: Baseline to Day 99 or ET
Caregiver Global Impression Of Change (CGIC) At The Last Visit
On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: "Very Much Improved"; "Much Improved"; "Slightly Improved"; "No Change"; "Slightly Worse"; "Much Worse"; "Very Much Worse". The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.
Time frame: Baseline to Last Visit
A total of 43 sites screened participants and 38 sites (23 in the United States, 7 in Spain, 3 in Poland, 2 in Australia, 1 in Israel, and 2 in the Netherlands) randomized participants into the trial. Two sites selected (1 in Israel and 1 in the United States) did not screen any participants.
| Milestone | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control |
|---|---|---|---|
| Started | 67 | 67 | 65 |
| Received at least 1 dose of study drug | 66 | 67 | 65 |
| Safety analysis set | 64 | 69 | 65 |
| Intent to treat (itt) analysis set | 66 | 67 | 65 |
| Completed | 64 | 61 | 65 |
| Not completed | 3 | 6 | 0 |
| Withdrew: Adverse event | 0 | 5 | 0 |
| Withdrew: Withdrawn by investigator | 1 | 0 | 0 |
| Withdrew: Advised by medical monitor | 1 | 0 | 0 |
| Withdrew: Withdrawn by parent/guardian | 0 | 1 | 0 |
| Withdrew: Lack of efficacy | 1 | 0 | 0 |
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.
| percentage reduction | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control |
|---|---|---|---|
| Change In Convulsive Seizures During The Treatment Period Compared To Baseline | 48.7 (37.9 to 57.6) | 45.7 (34.2 to 55.2) | 26.9 (11.9 to 39.4) |
Total seizures were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic seizures. Non-convulsive seizures were defined as myoclonic, countable partial, other partial, or absence seizures. Participants or their caregivers recorded the number and type of convulsive seizures and non-convulsive seizures each day from screening until completion of dosing using an IVRS diary. Change compared to baseline was calculated as per the primary outcome measure. Data reported as the ratio of geometric least squares mean in total seizures and expressed as a percentage reduction.
| percentage reduction | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control |
|---|---|---|---|
| Change In Total Seizures During The Treatment Period Compared To Baseline | 56.4 (47.8 to 63.6) | 47.3 (36.9 to 56.0) | 29.7 (16.0 to 41.1) |
Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an IVRS diary. Baseline included all available data prior to Day 1 (28-day average). Percentage change from baseline was calculated as: (\[frequency during the treatment period - frequency during baseline\]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average).
| Participants | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control |
|---|---|---|---|
| Participants With A ≥50% Reduction From Baseline In Convulsive Seizure Frequency During The Treatment Period | 29 | 33 | 17 |
On Day 1 (prior to receiving study drug), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the CGIC questionnaire at subsequent visits. The CGIC questionnaire comprised the following question, to be rated on a 7-point scale: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The markers were: "Very Much Improved"; "Much Improved"; "Slightly Improved"; "No Change"; "Slightly Worse"; "Much Worse"; "Very Much Worse". The CGIC response/score, recorded at each visit, was summarized, on both a categorical and continuous scale, by treatment group. The scores at the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed were analyzed using ordinal logistic regression.
| Participants | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control |
|---|---|---|---|
| Very Much Improved | 13 | 11 | 1 |
| Much Improved | 11 | 10 | 8 |
| Slightly Improved | 21 | 19 | 18 |
| No Change | 18 | 17 | 32 |
| Slightly Worse | 2 | 5 | 4 |
| Much Worse | 1 | 3 | 2 |
| Very Much Worse | 0 | 1 | 0 |
Collected over From Day 1 to Day 137.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 10 mg/kg/Day GWP42003-P | 0/64 (0%) | 13/64 (20.3%) | 56/64 (87.5%) |
| 20 mg/kg/Day GWP42003-P | 0/69 (0%) | 17/69 (24.6%) | 60/69 (87%) |
| Placebo Control | 0/65 (0%) | 10/65 (15.4%) | 58/65 (89.2%) |
| Event | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control |
|---|---|---|---|
| Status epilepticusNervous system disorders | 5/64 | 7/69 | 8/65 |
| ConvulsionNervous system disorders | 3/64 | 0/69 | 1/65 |
| PneumoniaInfections and infestations | 3/64 | 2/69 | 0/65 |
| SomnolenceNervous system disorders | 2/64 | 0/69 | 0/65 |
| Seizure clusterNervous system disorders | 1/64 | 0/69 | 2/65 |
| Pneumonia aspirationRespiratory, thoracic and mediastinal disorders | 1/64 | 2/69 | 0/65 |
| PyrexiaGeneral disorders | 1/64 | 1/69 | 0/65 |
| Toxicity to various agentsInjury, poisoning and procedural complications | 1/64 | 1/69 | 0/65 |
| Decreased appetiteMetabolism and nutrition disorders | 1/64 | 1/69 | 0/65 |
| Unresponsive to stimuliNervous system disorders | 1/64 | 0/69 | 0/65 |
| Event | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control |
|---|---|---|---|
| Decreased appetiteMetabolism and nutrition disorders | 10/64 | 19/69 | 11/65 |
| DiarrhoeaGastrointestinal disorders | 11/64 | 18/69 | 8/65 |
| PyrexiaGeneral disorders | 15/64 | 14/69 | 11/65 |
| SomnolenceNervous system disorders | 14/64 | 16/69 | 9/65 |
| FatigueGeneral disorders | 5/64 | 14/69 | 7/65 |
| VomitingGastrointestinal disorders | 4/64 | 11/69 | 4/65 |
| NasopharyngitisInfections and infestations | 4/64 | 8/69 | 5/65 |
| Alanine aminotransferase increasedInvestigations | 3/64 | 8/69 | 0/65 |
| Aspartate aminotransferase increasedInvestigations | 3/64 | 8/69 | 0/65 |
| AggressionPsychiatric disorders | 1/64 | 6/69 | 2/65 |
| Age, Continuous(Years) | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control | Total |
|---|---|---|---|---|
| Mean | 9.169 ± 4.1744 | 9.245 ± 4.3792 | 9.617 ± 4.5757 | 9.343 ± 4.3626 |
| Sex: Female, Male(Participants) | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control | Total |
|---|---|---|---|---|
| Female | 38 | 32 | 34 | 104 |
| Male | 26 | 37 | 31 | 94 |
| Race/Ethnicity, Customized(Participants) | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 1 | 1 |
| Asian | 0 | 1 | 4 | 5 |
| Black or African American | 1 | 0 | 4 | 5 |
| White | 55 | 66 | 55 | 176 |
| Other | 8 | 2 | 1 | 11 |
| Region of Enrollment(participants) | 10 mg/kg/Day GWP42003-P | 20 mg/kg/Day GWP42003-P | Placebo Control | Total |
|---|---|---|---|---|
| Australia | 6 | 4 | 3 | 13 |
| Israel | 0 | 1 | 2 | 3 |
| Netherlands | 9 | 7 | 9 | 25 |
| Poland | 8 | 11 | 6 | 25 |
| Spain | 12 | 14 | 13 | 39 |
| United States | 29 | 32 | 32 | 93 |
Documents are hosted by the registry — open the source record to download them.
Ran from Apr 2015 to primary completion in Apr 2018, 35 months.
Results were first posted in Aug 2019, 1 year 3 months after primary completion.
Of 49 industry-sponsored phase 3 interventional studies under Epilepsy, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 37 and three quarters within 88. This study's 35 months is below that.
Counting every sponsor, half of 67 studies reached it within 55 months; a quarter within 35 and three quarters within 88.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Cannabidiol