This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for An Open-label Extension Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6) (NCT02544750), a na phase 3 study. The primary outcome is Number of Participants With Any Treatment-emergent Adverse Events, Discontinuations Due to AEs, Serious AEs, and Treatment-related AEs (TEAE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02544750 |
| Phase | Phase 3 |
| Condition | Tuberous Sclerosis Complex, Seizures |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 199 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Jazz Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants with tuberous sclerosis complex who experience inadequately controlled seizures were the intended population in the official study title. The registry record describes only the open-label extension phase. Its primary endpoint population is the OLE Safety Analysis Set; further detail about that set is not reported in the registry record.
Intervention
Participants received GWP42003-P, also identified as cannabidiol or CBD. The listed oral solution was 100 mg/mL and taken twice daily, in the morning and evening. Dosing could be adjusted according to investigator judgment, with a maximum of 50 mg/kg/day.
Comparator
The extension is described as a single-group, open-label phase in which participants received the same treatment. It therefore has no concurrent comparator within the extension. The adverse-event record also lists placebo and GWP42003-P groups from the double-blind phase; the registry warns that these are not a like-for-like control comparison.
Primary question
The primary endpoint concerns how many participants experienced treatment-emergent adverse events, discontinuations due to adverse events, serious adverse events, and treatment-related adverse events during the extension safety period. The registry record defines these event categories, but does not report the primary endpoint results. It therefore does not answer how often these outcomes occurred in the extension.
3. Trial Design
This is a Phase 3 study record for NCT02544750, titled “An Open-label Extension Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6).” The official title describes a double-blind, randomized, placebo-controlled study of CBD as add-on therapy, but the record explicitly says that only the open-label extension phase is described in this record. The distinction matters: the extension and the original double-blind phase are not the same study period for interpreting the posted information.
The extension is described as a single-group study with no masking. Participants received GWP42003-P, and investigators could subsequently increase or decrease a participant’s dose until an optimal dose was found. The listed formulation was an oral solution at 100 mg/mL, taken twice daily in the morning and evening. The maximum listed dose was 50 mg/kg/day, with a lower dose possible if the investigator judged that benefit or tolerability warranted it.
The registry lists enrollment as 199, and the study status as completed. The recorded start date is 2016-08-31 and the primary completion date is 2021-06-11. Those dates describe the registry record and do not, by themselves, establish the duration of treatment for any participant. The primary endpoint timeframe is described as OLE Day 1 up to 4 years.
The record lists six outcome measures and zero analyses. It names secondary outcomes concerning percent change in TSC-associated seizure frequency, treatment responders, caregiver and subject global impression scores, and total seizure frequency. Results for these measures are not reported in the registry record. The design details of the original double-blind phase, including its allocation and analysis, should not be inferred from the extension record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: OLE investigational medicinal product (IMP) was titrated up to 25 mg/kg/day while blinded IMP was simultaneously tapered down to zero to accommodate those participants who had been randomized to placebo during the double-blind phase (DBP) of the study. All participants were to complete the transition and enter the OLE taking 25 mg/kg/day GWP42003-P.
Overall Study
| Stage | GWP42003-P (Double-blind Phase) | Placebo (Double-blind Phase) |
|---|---|---|
| STARTED | 124 | 75 |
| COMPLETED | 22 | 12 |
| NOT COMPLETED | 102 | 63 |
Reasons for not completing this period:
| Reason | GWP42003-P (Double-blind Phase) | Placebo (Double-blind Phase) |
|---|---|---|
| Physician Decision | 3 | 1 |
| Other reasons | 69 | 39 |
| Met withdrawal criteria | 2 | 2 |
| Transition To Commercial Product | 1 | 0 |
| Withdrawal by Parent/Guardian | 8 | 7 |
| Adverse Event | 8 | 10 |
| Withdrawal by Subject | 10 | 4 |
| Lost to Follow-up | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Adverse events were assessed in the OLE Safety Analysis Set.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | GWP42003-P (Double-blind Phase) | Placebo (Double-blind Phase) | Total |
|---|---|---|---|---|
| Participants analysed | 124 | 75 | 199 | |
| Age, Continuous | years | 12.69 (SD 9.64) | 13.92 (SD 10.63) | 13.15 (SD 10.02) |
| Sex: Female, Male: Female | Participants | 51 | 30 | 81 |
| Sex: Female, Male: Male | Participants | 73 | 45 | 118 |
| Race/Ethnicity, Customized: White/Caucasian | Participants | 111 | 66 | 177 |
| Race/Ethnicity, Customized: Black/African American | Participants | 4 | 0 | 4 |
| Race/Ethnicity, Customized: American Indian/Alaska Native | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Asian | Participants | 1 | 3 | 4 |
| Race/Ethnicity, Customized: Other | Participants | 7 | 6 | 13 |
| Baseline Tuberous Sclerosis Complex (TSC)-Associated Seizures | Seizures | 58.08 (7.7 to 432.0) | 55.10 (8.0 to 558.0) | 56.90 (7.7 to 558.0) |
| Baseline Total Seizures | Seizures | 59.95 (7.7 to 595.0) | 56.97 (8.0 to 1660.1) | 58.90 (7.7 to 1660.1) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Any Treatment-emergent Adverse Events, Discontinuations Due to AEs, Serious AEs, and Treatment-related AEs (TEAE), measured over OLE Day 1 up to 4 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants in four adverse-event categories: those with any treatment-emergent adverse event, discontinuations due to adverse events, serious adverse events, and treatment-related adverse events. A count endpoint describes how many participants in the defined safety population had an event in a category. It is not a measure of seizure reduction or a direct comparison of treatment efficacy.
The registry defines an adverse event broadly as a new unfavorable or unintended sign, symptom, abnormal laboratory finding, diagnosis, or worsening of a pre-existing condition arising after screening and up to the post-treatment safety follow-up visit. An event that began or worsened in severity or seriousness after the first dose was considered treatment-emergent. A serious adverse event was defined by outcomes including death, life-threatening experience, hospitalization or its prolongation, persistent or significant disability, congenital anomaly or birth defect, cancer, or other events meeting the stated seriousness criteria.
Collecting these categories is useful for describing safety during treatment and follow-up. Separating serious events from other treatment-emergent events also distinguishes events meeting the registry’s seriousness definition from the broader group. However, a count alone does not establish that treatment caused an event: the record’s definition allows that an adverse event may or may not be related to the investigational medicinal product. The registry identifies the OLE Safety Analysis Set as the endpoint population but does not report the endpoint counts or the number analyzed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record defines the primary safety endpoint but does not report its results. There are no posted counts for extension participants with treatment-emergent events, discontinuations due to adverse events, serious adverse events, or treatment-related adverse events. Consequently, the endpoint’s frequency and precision cannot be assessed from this record. The absence of results in the record is not evidence that no events occurred.
The adverse-event information that is present is explicitly labeled for the double-blind phase, not the open-label extension phase described by this record. It lists a placebo group with 38 participants with serious adverse events among 124 at risk, and a GWP42003-P group with 18 participants with serious adverse events among 75 at risk. It also lists one death in the placebo group and zero in the GWP42003-P group. The record cautions that this is not a randomized comparison and that the groups are not a like-for-like control comparison. These figures should therefore not be treated as an estimate of the extension’s safety outcomes or as a reliable causal contrast.
The listed serious-event terms include Seizure at 9.7%, Status epilepticus at 7.3%, Influenza at 4.0%, Pneumonia at 3.2%, Dehydration at 3.2%, and Transaminases increased at 2.7%. These are registry-listed terms and percentages for the adverse-event information; they do not replace the missing extension endpoint results. The record does not explain in the available information the denominator used for each term or whether participants could contribute to more than one term, so the percentages should not be summed or treated as mutually exclusive categories.
The study’s open-label, single-group extension design can describe events and outcomes observed during continued treatment, but it cannot by itself separate treatment effects from changes over time, background conditions, concomitant care, or other explanations. Dose adjustment also means that exposure could vary according to investigator judgment. That flexibility may be relevant to tolerability and treatment management, but the record does not report dose histories or results by dose.
Secondary outcomes are named, but their results are not reported in the registry record. Without those results, the record does not establish the direction, magnitude, or precision of any seizure-frequency or global-impression changes. No inferential analysis is listed. Interpretation should therefore remain limited to the stated design, endpoint definitions, and the adverse-event figures identified as coming from the double-blind phase.
9. Statistical Methods Explained
Statistical interpretation depends first on identifying the population, study period, and type of outcome. The primary endpoint is a count of participants with specified safety events, assessed in the OLE Safety Analysis Set. Its stated timeframe is OLE Day 1 up to 4 years. These details define what the endpoint is intended to cover; they do not supply the result. The registry record does not report the primary endpoint counts, an estimate of uncertainty, or an analysis for that endpoint.
What does a participant count describe?
A count records how many participants meet an outcome definition. For an event outcome, this answers a descriptive question about observed participants, not necessarily a causal question about treatment. A count is easier to interpret when its population and observation period are clear. A denominator can contextualize a count, but comparisons also depend on how participants were selected, followed, and exposed to treatment. In this record, the defined extension safety population is named, but the primary endpoint result and the number analyzed are not reported.
The endpoint includes several categories that should be kept conceptually distinct. Treatment-emergent refers to when an event began or worsened in relation to the first dose. Seriousness is based on the stated clinical consequences and criteria. Treatment-relatedness concerns an attribution to the investigational product. An event may be treatment-emergent without being serious, and an event’s timing does not by itself establish its cause. The registry definition explicitly allows that an adverse event may or may not be related to the investigational medicinal product.
What can an open-label, single-group extension show?
In general, an open-label extension can describe outcomes observed among participants receiving treatment over time. Without a concurrent control group in the extension, an observed change cannot automatically be attributed to treatment. Natural variation in disease, changes in other care, participant selection, and changes in observation can also contribute to patterns over time. These are general interpretive considerations, not findings about this trial.
Here, the extension is recorded as single-group and unmasked, and the summary says all participants receive the same treatment while investigators may adjust the dose. Such adjustment means a participant’s exposure is not necessarily fixed at one level throughout the extension. Dose changes may reflect investigator judgments about benefit or tolerability. To assess outcomes by exposure, details on actual doses, timing, and reasons for adjustment would be needed; those details are not reported in the registry record.
How should precision be understood?
In general, a confidence interval expresses the range of values compatible with the observed data under a statistical model and indicates the precision of an estimate. Narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. For event counts, precision depends on the number of observed events and the population contributing data. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated from the posted endpoint information.
For outcomes based on counts or rates, over-dispersion is a general concern when observed variation exceeds what a simple statistical model expects. A model that does not account for such variation can produce uncertainty estimates that are too optimistic. This is a general point about count-data analysis, not a statement that over-dispersion occurred in this trial. The registry record does not report a model for the primary endpoint, and it would be inappropriate to assume one.
What do the planning assumptions mean?
The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated target effect is a fraction of the observed effect. These are planning assumptions, not evidence that the extension itself was designed as a two-arm comparison, and not a description of the extension’s observed results. The record cautions that sample-size illustrations are planning tools rather than observed power.
In general, a significance level is a threshold used in a specified testing procedure; it does not measure the probability that a treatment works or the importance of an outcome. A sample-size calculation depends on assumptions about the effect, variability, allocation, and analysis. It is not a substitute for the observed estimate and its uncertainty. The registry record does not report the trial’s own sample-size justification or statistical plan, and no calculated sample-size values are included in the available record details.
What can be inferred from the listed analysis information?
The registry record lists zero analyses. This means the record does not give an analysis result for the named outcomes; it does not establish that no analysis was conducted outside the registry record. The secondary endpoints identify subjects of interest, including seizure frequency, responder status, and global impressions, but the outcome definitions and results needed to evaluate their statistical treatment are not reported. No adjustment method, inferential model, or confidence interval should be inferred from the endpoint names alone.
The serious-event groups are labeled as belonging to the double-blind phase. Their counts are descriptive registry entries for that phase, and the record itself warns against treating the groups as a like-for-like control comparison. General principles of randomized comparisons therefore should not be used to imply that these particular figures provide a valid treatment-effect estimate for the extension. Study phase and analysis population must match the question before a statistical contrast can be interpreted.
10. Multiplicity, Missing Data and Analysis Populations
The registry names multiple outcomes: the primary safety endpoint and secondary measures involving TSC-associated seizure frequency, responder status, caregiver and subject global impressions, and total seizure frequency. The record lists six outcome measures, but does not report their results or a multiplicity strategy. When several outcomes are tested, general statistical practice considers the possibility that some apparently notable results may arise by chance across the collection of tests. Methods to address this can include specifying a hierarchy or adjusting the interpretation of tests. Which approach, if any, was used is not reported in the registry record.
Missing-data handling is also not reported in the registry record. The available information does not describe how incomplete follow-up, missed assessments, or withdrawal from treatment were handled for the primary or secondary outcomes. Nor does it state whether any imputation, sensitivity analysis, or other approach was used. These omissions limit interpretation because the observed data may not represent all participants’ experience equally when follow-up is incomplete.
The primary endpoint names the OLE Safety Analysis Set, but further membership criteria and the number analyzed are not reported. Analysis populations for the secondary outcomes are not reported in the registry record. The record lists zero analyses, so it does not provide an analysis plan or outcome-specific statistical methods. These gaps do not establish that the study lacked such procedures; they mean that the procedures cannot be evaluated from the registry record.
The planning illustration’s significance level and allocation assumptions are not a substitute for a prespecified multiplicity plan or missing-data method. They describe assumptions for a planning calculation, not the analysis of the extension’s posted outcomes.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo (Double-blind Phase) | 38 | 124 | 30.6% |
| GWP42003-P (Double-blind Phase) | 18 | 75 | 24.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo (Double-blind Phase) | 1 of 124 |
| GWP42003-P (Double-blind Phase) | 0 of 75 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo (Double-blind Phase) | 117 of 124 |
| GWP42003-P (Double-blind Phase) | 75 of 75 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo (Double-blind Phase) | GWP42003-P (Double-blind Phase) |
|---|---|---|---|
| Seizure | Nervous system disorders | 12 of 124 | 4 of 75 |
| Status epilepticus | Nervous system disorders | 9 of 124 | 1 of 75 |
| Dehydration | Metabolism and nutrition disorders | 4 of 124 | 2 of 75 |
| Influenza | Infections and infestations | 5 of 124 | 0 of 75 |
| Pneumonia | Infections and infestations | 4 of 124 | 1 of 75 |
| Adenovirus infection | Infections and infestations | 2 of 124 | 0 of 75 |
| Toxicity to various agents | Injury, poisoning and procedural complications | 1 of 124 | 1 of 75 |
| Alanine aminotransferase increased | Investigations | 1 of 124 | 1 of 75 |
| Aspartate aminotransferase increased | Investigations | 1 of 124 | 1 of 75 |
| Liver function test increased | Investigations | 1 of 124 | 1 of 75 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo (Double-blind Phase) | GWP42003-P (Double-blind Phase) |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 50 of 124 | 43 of 75 |
| Seizure | Nervous system disorders | 40 of 124 | 19 of 75 |
| Pyrexia | General disorders | 33 of 124 | 15 of 75 |
| Decreased appetite | Metabolism and nutrition disorders | 23 of 124 | 24 of 75 |
| Vomiting | Gastrointestinal disorders | 27 of 124 | 13 of 75 |
| Somnolence | Nervous system disorders | 15 of 124 | 24 of 75 |
| Nasopharyngitis | Infections and infestations | 19 of 124 | 16 of 75 |
| Upper respiratory tract infection | Infections and infestations | 22 of 124 | 10 of 75 |
| Cough | Respiratory, thoracic and mediastinal disorders | 13 of 124 | 13 of 75 |
| Constipation | Gastrointestinal disorders | 12 of 124 | 9 of 75 |
Serious events with the highest arm-level rate: seizure (9.7%), status epilepticus (7.3%), influenza (4.0%), pneumonia (3.2%), dehydration (3.2%).
The serious adverse-event figures are labeled for the double-blind phase. The placebo group lists 38 participants with serious adverse events among 124 at risk; the GWP42003-P group lists 18 among 75 at risk. The registry also lists one death for the placebo group and zero for the GWP42003-P group. These are descriptive entries, not results for the open-label extension’s primary safety endpoint.
The record cautions that the arms are not a like-for-like control comparison. They should not be used to claim a treatment difference or to estimate the extension’s event frequency. The serious-event terms listed include Seizure (9.7%), Status epilepticus (7.3%), Influenza (4.0%), Pneumonia (3.2%), Dehydration (3.2%), and Transaminases increased (2.7%). The record does not provide enough detail to determine whether these term percentages overlap or to establish their denominator, so they should be read as listed, not added together.
The extension endpoint results for serious adverse events and the other stated safety categories are not reported in the registry record. Adverse-event reporting is descriptive and does not, on its own, establish whether treatment caused an event.
12. What the Result Does, and Does Not, Mean
The registry record establishes that an open-label extension of GWP42003-P was conducted for participants with tuberous sclerosis complex and seizures, and it defines a safety endpoint covering treatment-emergent events, adverse-event discontinuations, serious events, and treatment-related events. It also describes the oral dosing schedule and the possibility of investigator-directed dose adjustment. These registry entries characterize the study question and how treatment was administered, but they are not evidence of a particular outcome.
The primary endpoint results are not reported in the registry record. The listed secondary outcomes also lack reported results. Therefore, this record does not show the frequency of the extension’s adverse events, the degree of any seizure-frequency change, the number of treatment responders, or caregiver or subject impression scores. It cannot establish the size or precision of a treatment-associated change.
The adverse-event counts and listed serious-event terms belong to the double-blind phase. The record explicitly warns that the groups are not a like-for-like control comparison. Those figures cannot be transferred to the extension or interpreted as a causal estimate for GWP42003-P. Even a descriptive count does not by itself show that a treatment caused an event.
More generally, an open-label, single-group extension can document observations during treatment but does not provide a concurrent untreated comparison within that extension. Without appropriate comparative evidence and a reported analysis, observed changes cannot be separated from other influences. This is a general design consideration, not a conclusion about the trial’s unreported results.
Accordingly, the registry record supports a description of the extension design, its endpoint definitions, and the limitations of the posted safety information. It does not support a conclusion about efficacy or a complete assessment of extension safety. Missing results should be treated as unreported information, not as evidence of either favorable or unfavorable outcomes.
13. Why This Trial Matters Statistically
This study is statistically relevant because it illustrates the importance of matching a result to the study phase and population that produced it. The registry record focuses on an open-label extension, yet the adverse-event information names placebo and GWP42003-P groups from the double-blind phase. Those entries answer a different descriptive question from the extension’s primary endpoint. The record’s warning that the arms are not a like-for-like control comparison is essential to interpreting them.
The design also demonstrates why a safety endpoint needs a clear event definition and observation period. Treatment-emergent status is based on event timing relative to first dose, while seriousness is based on specified consequences and criteria, and treatment-relatedness concerns attribution. These distinctions help prevent the mistaken assumption that every event arising during treatment was caused by treatment or was serious.
Finally, the record shows the difference between naming outcomes and reporting analyses. It identifies safety and seizure-related measures, but does not report their results or analysis methods. Without estimates and measures of uncertainty, readers cannot assess the magnitude or precision of outcomes. Without a reported comparison suited to the design, they cannot interpret an observed pattern as a treatment effect. These are general principles of clinical-trial interpretation, applied to the information recorded for this extension.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation is the mismatch between the record’s stated focus and the adverse-event groups listed. The record describes the open-label extension, while the available group counts are labeled as from the double-blind phase. The registry specifically cautions that these arms are not a like-for-like control comparison. As a result, those counts cannot answer the extension’s primary safety question.
The extension is described as single-group and unmasked. There is no concurrent comparator within that phase, limiting the ability to distinguish treatment-associated changes from other influences. Investigators could adjust doses in response to benefit or tolerability judgments, but actual dose histories and outcome results by dose are not reported in the registry record.
The primary safety endpoint is defined and assigned to the OLE Safety Analysis Set, but its results and the number analyzed are not reported. Secondary outcomes are named without results. The record lists zero analyses, and does not report the statistical analysis plan, missing-data methods, multiplicity handling, or detailed analysis-population criteria. These items should be treated as not reported in the registry record, rather than assumed absent from the conduct of the study.
The record’s serious-event term percentages lack further denominator and overlap detail in the information available for interpretation. They should not be summed or treated as mutually exclusive categories. Finally, the registry enrollment value does not establish how many participants contributed data to each endpoint or how long each participant was followed. Endpoint-specific participation and follow-up results are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open-label Extension Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6) — NCT02544750.
- Registry record last updated 2022-07-14; status last verified 2022-07.
- Results first posted 2022-07-14.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02544750 is a completed Phase 3 record for an open-label extension of GWP42003-P (CBD) in tuberous sclerosis complex and seizures. It describes a single-group, unmasked extension with twice-daily oral dosing and investigator-directed dose adjustment up to the listed maximum of 50 mg/kg/day. The primary endpoint concerns counts of participants with specified adverse-event outcomes in the OLE Safety Analysis Set.
The registry record does not report the primary endpoint results or results for the named secondary outcomes, and it lists zero analyses. The serious adverse-event counts and terms that are reported are labeled as coming from the double-blind phase; the registry cautions that those groups are not a like-for-like control comparison. They should not be interpreted as extension results or as a causal treatment comparison.