Seizure in Participants With Tuberous Sclerosis Complex, Seizure in Participants With Dravet Syndrome, Seizure in Participants With Lennox-Gastaut Syndrome
Conditions
Keywords
Epilepsy, Seizures, Infantile Spasms, Pediatric, Children, Infants, Cannabidiol oral solution, GWP42003-P, Tuberous Sclerosis Complex, TSC, Tuberous Sclerosis, Cannabidiol, Epidiolex, CBD, Seizure, Child, TSC1, TSC2, Tuberous Sclerosis 1, Tuberous Sclerosis 2, Lennox-Gastaut Syndrome, Dravet Syndrome
Brief summary
This study will be conducted to evaluate the safety, pharmacokinetics (PK), and efficacy of adjunctive GWP42003-P in participants \< 2 years of age with tuberous sclerosis complex (TSC), Lennox-Gastaut syndrome (LGS), or Dravet syndrome (DS).
Detailed description
The study duration will be up to approximately 62 weeks, including a 4-week screening/baseline period, a 52-week dose optimization treatment period (which includes a fixed 2-week titration period followed by flexible dose optimization), a 10-day taper period, and a safety follow-up period (4 weeks after the end-of-taper visit).
Interventions
DRUGGWP42003-P
Oral Solution
Sponsors
Jazz Pharmaceuticals Research UK Limited
Jazz Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 23 Months
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants with TSC (1 month to \< 2 years of age), or DS (1 year to \< 2 years of age), or LGS (1 year to \< 2 years of age) within the specified age range at the time of initial informed consent. * Parent(s)/legal representative is/are willing and able to give informed consent for participation in the study. * Parent(s)/legal representative is/are willing and able (in the investigator's opinion) to comply with all study requirements (including accurate electronic participant-reported outcome \[ePRO\] diary completion). * Participants with TSC must have a diagnosis per the 2012 International Tuberous Sclerosis Complex Consensus Conference. Participants with LGS or DS must have a diagnosis that is consistent with International League Against Epilepsy (ILAE) guidelines and confirmed by the Epilepsy Study Consortium (ESCI). * Participants who have uncontrolled seizures, and who are currently receiving 1 or more antiseizure medication (ASMs). * A suitable VEEG, as available in the medical record, within 1 year of Visit 1. When a historical VEEG is not available, and if clinically indicated and appropriate (due to uncertainties or new seizures), a VEEG will be completed and read to confirm diagnosis prior to Visit 3. All VEEGs are to be read at baseline by the investigator and by an independent reviewer. * Has seizures which are not adequately controlled through their current ASMs, defined as ≥ 1 seizure reported on the seizure diary during the screening/baseline period Key
Exclusion criteria
* Has tumor growth which, in the opinion of the investigator, could affect participant safety. * Has clinically significant abnormal laboratory values, in the investigator's opinion, at screening/baseline. * Has clinically significant abnormalities in the electrocardiogram (ECG) measured at screening/baseline. * Has any concurrent cardiovascular conditions, that will, in the investigator's opinion, interfere with the ability to assess their ECGs. * Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study intervention such as sesame seed oil. * Has significantly impaired hepatic function prior to Visit 3, defined as: * Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × upper limit of normal (ULN) and (total bilirubin \[TBL\] \> 2 × ULN or international normalized ratio \[INR\] \> 1.5). * Serum ALT or AST \> 5 × ULN. * Serum ALT or AST \> 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (\> 5%). * Elevated ALT or AST should be discussed with the medical monitor prior to Visit 3; the medical monitor may allow for a confirmatory re-draw prior to Visit 3. * Has received another study intervention within 4 weeks prior to Visit 1 or plans to take another study intervention during the study. * Has any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant, other participants, or site staff at risk because of participation in the study, may influence the result of the study, or may affect the participant's ability to take part in the study. * Any clinically significant abnormalities identified following a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if they took part in the study. * Has previously been enrolled into this study. * Has plans to travel outside their country of residence during the study, unless the participant has confirmation that the study intervention is permitted in the destination country. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician Global Impression of Change (CGI/C) Score | At Day 365 (EOT) | The CGI/C is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores are reported. The severity of impairment in each domain is rated by the clinician in a scale of 1 through 7 where 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill. Higher scores indicate poor clinical outcome. |
| Number of Participants With a Clinically Significant Change in Laboratory Parameters | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Number of Participants With Emergence of New Types of Seizures | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Plasma Concentrations of GWP42003-P and Its Major Metabolites | Predose, 3 hours and 6 hours post dose at End of Treatment (Week 52) | — |
| Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1 up to Taper Period, up to Week 52 | — |
| Clinician Global Impression of Severity (CGI/S) Score | At Day 365 (EOT) | The CGIC/S is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores are reported. The severity of impairment in each domain is rated by the clinician in a scale of 1 through 7 where 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill. Higher scores indicate poor clinical outcome. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From start of treatment to the post-treatment safety follow-up visit, up to 62 weeks | — |
| Mean Change From Baseline in Blood Pressure | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in Pulse Rate | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in Respiratory Rate | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in Body Temperature | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in Height | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in Body Weight | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in Heart Rate | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in RR Interval | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in PR Interval | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in QRS Duration | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in QT Interval | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
| Mean Change From Baseline in QTcB and QTcF | From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Responders | Day 1 up to the taper period, up to Week 52 | Treatment Responders are defined as participants with ≥ 50% reduction from baseline in caregiver-reported total countable seizures |
| Number of Participants Who Achieved Seizure-Free Status | Week 12, and every 4 weeks thereafter, up to date of withdrawal or Week 24, whichever occurs first | — |
| Percentage of Participants Still Receiving GWP42003-P | Week 12, and every 4 weeks thereafter, up to date of withdrawal or Week 24, whichever occurs first | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 1 up to Taper Period, up to Week 52 | — |
| Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | At Day 365 (EOT) | The Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) was developed for use in infants and toddlers from 12-months-to-5 years of age and assesses levels of health and well-being. The caregiver will complete the assessment on an electronic device. For each concept, item responses are scored, summed, and transformed on a scale from 0 (worst health) to 100 (best health). Higher scores indicate better clinical outcome. |
Countries
Italy, Spain, United States
Participant flow
Recruitment details
A total of 3 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at 3 sites in the United States.
Pre-assignment details
The study duration will be up to approximately 62 weeks, including a 4-week screening/baseline period, a 52-week dose optimisation treatment period (which includes a fixed 2-week titration period followed by flexible dose optimisation), a 10-day taper period, and a safety follow-up period (4 weeks after the end-of-taper visit).
Participants by arm
| Arm | Count |
|---|---|
| Tuberous Sclerosis Complex Participants with Tuberous Sclerosis Complex who received GWP42003-P orally twice daily (b.i.d.) on a titration schedule, with a starting dose of 5 mg/kg/day (2.5 mg/kg b.i.d.) on Day 1, then 10 mg/kg/day (5 mg/kg b.i.d.) on Day 8, followed by a flexible dose optimization from Day 15 to Week 52 based on the clinical judgment of the investigator. | 2 |
| Dravet Syndrome Participants with Dravet Syndrome who received GWP42003-P orally twice daily (b.i.d.) on a titration schedule, with a starting dose of 5 mg/kg/day (2.5 mg/kg b.i.d.) on Day 1, then 10 mg/kg/day (5 mg/kg b.i.d.) on Day 8, followed by a flexible dose optimization from Day 15 to Week 52 based on the clinical judgment of the investigator. | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Decision by sponsor | 0 | 1 |
| Overall Study | Physician Decision | 2 | 0 |
Baseline characteristics
| Characteristic | Tuberous Sclerosis Complex | Dravet Syndrome | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 1 / 2 | 1 / 1 |
| serious Total, serious adverse events | 2 / 2 | 0 / 1 |
Outcome results
Primary
Clinician Global Impression of Change (CGI/C) Score
The CGI/C is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores are reported. The severity of impairment in each domain is rated by the clinician in a scale of 1 through 7 where 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill. Higher scores indicate poor clinical outcome.
Time frame: At Day 365 (EOT)
Population: CGI-C was assessed and reported for the participant with Dravet Syndrome. As both participants with Tuberous Sclerosis Complex consented under a previous protocol version that did not include CGI-C, this assessment was not collected for these participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dravet Syndrome | Clinician Global Impression of Change (CGI/C) Score | Motor | 3.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Change (CGI/C) Score | Adaptive Functioning | 4.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Change (CGI/C) Score | Sensory | 3.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Change (CGI/C) Score | Cognition | 3.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Change (CGI/C) Score | Emotional/Behavioral | 3.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Change (CGI/C) Score | Communication | 4.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Change (CGI/C) Score | Social | 3.0 score on a scale |
Primary
Clinician Global Impression of Severity (CGI/S) Score
The CGIC/S is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores are reported. The severity of impairment in each domain is rated by the clinician in a scale of 1 through 7 where 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill. Higher scores indicate poor clinical outcome.
Time frame: At Day 365 (EOT)
Population: CGI-S was assessed and reported for the participant with Dravet Syndrome. As both participants with Tuberous Sclerosis Complex consented under a previous protocol version that did not include CGI S, this assessment was not collected for these participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dravet Syndrome | Clinician Global Impression of Severity (CGI/S) Score | Emotional/Behavioral | 3.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Severity (CGI/S) Score | Sensory | 3.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Severity (CGI/S) Score | Motor | 3.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Severity (CGI/S) Score | Cognition | 4.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Severity (CGI/S) Score | Communication | 4.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Severity (CGI/S) Score | Social | 1.0 score on a scale |
| Dravet Syndrome | Clinician Global Impression of Severity (CGI/S) Score | Adaptive Functioning | 1.0 score on a scale |
Primary
Mean Change From Baseline in Blood Pressure
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: Blood pressure was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in Blood Pressure | Systolic blood pressure | -3.0 mmHg | Standard Deviation 9.9 |
| Tuberous Sclerosis Complex | Mean Change From Baseline in Blood Pressure | Diastolic blood pressure | 13.5 mmHg | Standard Deviation 19.09 |
| Dravet Syndrome | Mean Change From Baseline in Blood Pressure | Systolic blood pressure | 11.0 mmHg | — |
| Dravet Syndrome | Mean Change From Baseline in Blood Pressure | Diastolic blood pressure | -2.0 mmHg | — |
Primary
Mean Change From Baseline in Body Temperature
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: Body temperature was assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in Body Temperature | -0.05 degrees Celsius | Standard Deviation 0.354 |
| Dravet Syndrome | Mean Change From Baseline in Body Temperature | -0.10 degrees Celsius | — |
Primary
Mean Change From Baseline in Body Weight
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: Body weight was assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in Body Weight | 0.15 kilogram | Standard Deviation 0.354 |
| Dravet Syndrome | Mean Change From Baseline in Body Weight | 0.60 kilogram | — |
Primary
Mean Change From Baseline in Heart Rate
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: Heart rate was assessed in participants with available data in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in Heart Rate | -10.0 beats/minute |
| Dravet Syndrome | Mean Change From Baseline in Heart Rate | 8.0 beats/minute |
Primary
Mean Change From Baseline in Height
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: Height was assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in Height | 1.95 centimeters | Standard Deviation 1.344 |
| Dravet Syndrome | Mean Change From Baseline in Height | 4.20 centimeters | — |
Primary
Mean Change From Baseline in PR Interval
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: PR interval was assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in PR Interval | 11.0 millisecond | Standard Deviation 12.73 |
| Dravet Syndrome | Mean Change From Baseline in PR Interval | -2.0 millisecond | — |
Primary
Mean Change From Baseline in Pulse Rate
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: Pulse rate was assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in Pulse Rate | -11.0 beats per minute | Standard Deviation 1.41 |
| Dravet Syndrome | Mean Change From Baseline in Pulse Rate | 11.0 beats per minute | — |
Primary
Mean Change From Baseline in QRS Duration
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: QRS duration was assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in QRS Duration | 3.0 millisecond | Standard Deviation 1.41 |
| Dravet Syndrome | Mean Change From Baseline in QRS Duration | 6.0 millisecond | — |
Primary
Mean Change From Baseline in QTcB and QTcF
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: QTcB and QTcF were assessed in participants with available data in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in QTcB and QTcF | QTcF | -4.0 millisecond |
| Tuberous Sclerosis Complex | Mean Change From Baseline in QTcB and QTcF | QTcB | -10.0 millisecond |
| Dravet Syndrome | Mean Change From Baseline in QTcB and QTcF | QTcF | 9.0 millisecond |
| Dravet Syndrome | Mean Change From Baseline in QTcB and QTcF | QTcB | 16.0 millisecond |
Primary
Mean Change From Baseline in QT Interval
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: QT interval was assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in QT Interval | 0 millisecond | Standard Deviation 8.49 |
| Dravet Syndrome | Mean Change From Baseline in QT Interval | 0 millisecond | — |
Primary
Mean Change From Baseline in Respiratory Rate
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: Respiratory rate was assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in Respiratory Rate | -10.0 breaths/minute | Standard Deviation 16.97 |
| Dravet Syndrome | Mean Change From Baseline in Respiratory Rate | 0 breaths/minute | — |
Primary
Mean Change From Baseline in RR Interval
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: RR interval was assessed in participants with available data in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tuberous Sclerosis Complex | Mean Change From Baseline in RR Interval | 48.0 millisecond |
| Dravet Syndrome | Mean Change From Baseline in RR Interval | -45.0 millisecond |
Primary
Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers
Time frame: Day 1 up to Taper Period, up to Week 52
Population: Indication-specific total countable seizures where assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: <= -50% to > -75% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: <= -25% to > -50% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: <= -25% to > -50% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: <= -50% to > -75% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: <= -50% to > -75% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: <= -75% (reduction) | 1 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: <= -50% to > -75% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: > 25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: <= -25% to > -50% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: >= 0% to <=25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: <= -75% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: > -25% to 0% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: > -25% to 0% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: <= -75% (reduction) | 1 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: >= 0% to <=25% (increase) | 1 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: > 25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: > 25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: >= 0% to <=25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: <= -50% to > -75% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: > -25% to 0% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: >= 0% to <=25% (increase) | 1 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: <= -25% to > -50% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: > 25% (increase) | 2 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: <= -50% to > -75% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: > -25% to 0% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: <= -75% (reduction) | 1 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: <= -25% to > -50% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: > 25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: <= -25% to > -50% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: >= 0% to <=25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: >= 0% to <=25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: > -25% to 0% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: <= -50% to > -75% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: <= -25% to > -50% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: <= -75% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: <= -50% to > -75% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: <= -75% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: <= -75% (reduction) | 1 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: <= -25% to > -50% change (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: > 25% (increase) | 1 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: > 25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: >= 0% to <=25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: > 25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: > -25% to 0% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: >= 0% to <=25% (increase) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: > -25% to 0% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: <= -75% (reduction) | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: <= -50% to > -75% change (reduction) | 1 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: <= -25% to > -50% change (reduction) | 1 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: <= -50% to > -75% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: > 25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: >= 0% to <=25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: <= -25% to > -50% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: <= -25% to > -50% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: > 25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: >= 0% to <=25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 1-29: <= -75% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: <= -25% to > -50% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: <= -50% to > -75% change (reduction) | 1 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 30-57: <= -75% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: > 25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: >= 0% to <=25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: <= -25% to > -50% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: <= -50% to > -75% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 58-85: <= -75% (reduction) | 1 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: > 25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: >= 0% to <=25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: <= -25% to > -50% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: <= -50% to > -75% change (reduction) | 1 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 86-113: <= -75% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: > 25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: >= 0% to <=25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 114-141: <= -75% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: > 25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: >= 0% to <=25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: <= -25% to > -50% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: <= -50% to > -75% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 142-169: <= -75% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: > 25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: >= 0% to <=25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: <= -25% to > -50% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: <= -50% to > -75% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Day 170-197: <= -75% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: > 25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: >= 0% to <=25% (increase) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: > -25% to 0% (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: <= -50% to > -75% change (reduction) | 0 participants |
| Dravet Syndrome | Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers | Taper Period: <= -75% (reduction) | 0 participants |
Primary
Number of Participants With a Clinically Significant Change in Laboratory Parameters
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: Clinically significant change in laboratory parameters were assessed in participants with available data in the Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tuberous Sclerosis Complex | Number of Participants With a Clinically Significant Change in Laboratory Parameters | Alanine aminotransferase | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants With a Clinically Significant Change in Laboratory Parameters | Aspartate aminotransferase | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants With a Clinically Significant Change in Laboratory Parameters | Gamma Glutamyltransferase | 0 participants |
| Dravet Syndrome | Number of Participants With a Clinically Significant Change in Laboratory Parameters | Alanine aminotransferase | 1 participants |
| Dravet Syndrome | Number of Participants With a Clinically Significant Change in Laboratory Parameters | Aspartate aminotransferase | 1 participants |
| Dravet Syndrome | Number of Participants With a Clinically Significant Change in Laboratory Parameters | Gamma Glutamyltransferase | 1 participants |
Primary
Number of Participants With Emergence of New Types of Seizures
Time frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Population: New types of seizures were assessed in the Safety Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tuberous Sclerosis Complex | Number of Participants With Emergence of New Types of Seizures | 1 participants |
| Dravet Syndrome | Number of Participants With Emergence of New Types of Seizures | 0 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From start of treatment to the post-treatment safety follow-up visit, up to 62 weeks
Population: Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tuberous Sclerosis Complex | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 2 participants |
| Dravet Syndrome | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 1 participants |
Primary
Plasma Concentrations of GWP42003-P and Its Major Metabolites
Time frame: Predose, 3 hours and 6 hours post dose at End of Treatment (Week 52)
Population: Pharmacokinetics were assessed and reported for participants when samples were collected. For both participants with Tuberous Sclerosis Complex, it was not possible to collect PK samples at 6hr post dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tuberous Sclerosis Complex | Plasma Concentrations of GWP42003-P and Its Major Metabolites | CBD (pre-dose) | 55.3 ng/mL | Standard Deviation 46.3 |
| Tuberous Sclerosis Complex | Plasma Concentrations of GWP42003-P and Its Major Metabolites | CBD (3-hour post-dose) | 456 ng/mL | — |
| Tuberous Sclerosis Complex | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-OH-CBD (pre-dose) | 37.8 ng/mL | Standard Deviation 29.7 |
| Tuberous Sclerosis Complex | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-OH-CBD (3-hour post-dose) | 161 ng/mL | — |
| Tuberous Sclerosis Complex | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-COOH-CBD (pre-dose) | 2790 ng/mL | Standard Deviation 884 |
| Tuberous Sclerosis Complex | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-COOH-CBD (3-hour post-dose) | 4870 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-OH-CBD (pre-dose) | 123 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-COOH-CBD (6-hour post-dose) | 9680 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-OH-CBD (3-hour post-dose) | 580 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-OH-CBD (6-hour post-dose) | 292 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | CBD (pre-dose) | 99.8 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-COOH-CBD (3-hour post-dose) | 10700 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | CBD (3-hour post-dose) | 427 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | CBD (6-hour post-dose) | 149 ng/mL | — |
| Dravet Syndrome | Plasma Concentrations of GWP42003-P and Its Major Metabolites | 7-COOH-CBD (pre-dose) | 7460 ng/mL | — |
Secondary
Number of Participants Who Achieved Seizure-Free Status
Time frame: Week 12, and every 4 weeks thereafter, up to date of withdrawal or Week 24, whichever occurs first
Population: Seizure free status is reported for the 2 participants that remained on the study for \> 12 weeks, and data are reported up to the timepoint prior to their withdrawal from the study. One participant with Tuberous Sclerosis Complex withdrew from the study prior to week 12 so their seizure free status could not be assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tuberous Sclerosis Complex | Number of Participants Who Achieved Seizure-Free Status | Week 20 | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Who Achieved Seizure-Free Status | Week 16 | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Who Achieved Seizure-Free Status | Week 24 | 0 participants |
| Tuberous Sclerosis Complex | Number of Participants Who Achieved Seizure-Free Status | Week 12 | 0 participants |
| Dravet Syndrome | Number of Participants Who Achieved Seizure-Free Status | Week 16 | 0 participants |
| Dravet Syndrome | Number of Participants Who Achieved Seizure-Free Status | Week 12 | 0 participants |
| Dravet Syndrome | Number of Participants Who Achieved Seizure-Free Status | Week 20 | 0 participants |
Secondary
Number of Treatment Responders
Treatment Responders are defined as participants with ≥ 50% reduction from baseline in caregiver-reported total countable seizures
Time frame: Day 1 up to the taper period, up to Week 52
Population: Treatment response was assessed and reported for participants with available data. The participant with Dravet Syndrome was not assessed at the last 3 timepoints due to early withdrawal from the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tuberous Sclerosis Complex | Number of Treatment Responders | Taper Period | 0 participants |
| Tuberous Sclerosis Complex | Number of Treatment Responders | Day 86-113 | 1 participants |
| Tuberous Sclerosis Complex | Number of Treatment Responders | Day 114-141 | 1 participants |
| Tuberous Sclerosis Complex | Number of Treatment Responders | Day 142-169 | 1 participants |
| Tuberous Sclerosis Complex | Number of Treatment Responders | Day 170-197 | 1 participants |
| Tuberous Sclerosis Complex | Number of Treatment Responders | Day 1-29 | 0 participants |
| Tuberous Sclerosis Complex | Number of Treatment Responders | Day 30-57 | 0 participants |
| Tuberous Sclerosis Complex | Number of Treatment Responders | Day 58-85 | 0 participants |
| Dravet Syndrome | Number of Treatment Responders | Day 1-29 | 0 participants |
| Dravet Syndrome | Number of Treatment Responders | Day 114-141 | 1 participants |
| Dravet Syndrome | Number of Treatment Responders | Day 30-57 | 1 participants |
| Dravet Syndrome | Number of Treatment Responders | Day 86-113 | 1 participants |
| Dravet Syndrome | Number of Treatment Responders | Day 58-85 | 1 participants |
Secondary
Percentage of Participants Still Receiving GWP42003-P
Time frame: Week 12, and every 4 weeks thereafter, up to date of withdrawal or Week 24, whichever occurs first
Population: Percentage of participants still receiving GWP42003-P is reported to the point at which subjects terminated their treatment and withdrew from the study. One participant with Tuberous Sclerosis Complex withdrew from the study prior to week 12. One participant with Tuberous Sclerosis Complex withdrew following the Day 170-197 timepoint. The participant with Dravet Syndrome withdrew following the Day 142-169 timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tuberous Sclerosis Complex | Percentage of Participants Still Receiving GWP42003-P | Week 12 | 50 percentage of participants |
| Tuberous Sclerosis Complex | Percentage of Participants Still Receiving GWP42003-P | Week 16 | 50 percentage of participants |
| Tuberous Sclerosis Complex | Percentage of Participants Still Receiving GWP42003-P | Week 20 | 50 percentage of participants |
| Tuberous Sclerosis Complex | Percentage of Participants Still Receiving GWP42003-P | Week 24 | 50 percentage of participants |
| Dravet Syndrome | Percentage of Participants Still Receiving GWP42003-P | Week 24 | 0 percentage of participants |
| Dravet Syndrome | Percentage of Participants Still Receiving GWP42003-P | Week 12 | 100 percentage of participants |
| Dravet Syndrome | Percentage of Participants Still Receiving GWP42003-P | Week 20 | 100 percentage of participants |
| Dravet Syndrome | Percentage of Participants Still Receiving GWP42003-P | Week 16 | 100 percentage of participants |
Other Pre-specified
Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score
The Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) was developed for use in infants and toddlers from 12-months-to-5 years of age and assesses levels of health and well-being. The caregiver will complete the assessment on an electronic device. For each concept, item responses are scored, summed, and transformed on a scale from 0 (worst health) to 100 (best health). Higher scores indicate better clinical outcome.
Time frame: At Day 365 (EOT)
Population: ITQOL-47 score was assessed in participants with available data in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Overall Health Score | 25.0 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Bodily Pain/Discomfort Zone | 0 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Combined Behavior Scale | 17.90 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Change in Health Score | 0 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Family Cohesion Score | -55.0 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Growth and Development Score | 5.0 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | General Health Perceptions Score | -20.0 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Physical Abilities Score | 11.10 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Parental Impact-Emotional Score | -25.00 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Parental Impact-Time Score | 0 score on a scale |
| Tuberous Sclerosis Complex | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Temperament and Moods Score | -8.30 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Parental Impact-Emotional Score | 12.50 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | General Health Perceptions Score | -20.0 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Bodily Pain/Discomfort Zone | 12.50 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Overall Health Score | 0 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Combined Behavior Scale | 0 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Temperament and Moods Score | 4.20 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Change in Health Score | 1.0 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Physical Abilities Score | -5.60 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Family Cohesion Score | 15.0 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Parental Impact-Time Score | 8.30 score on a scale |
| Dravet Syndrome | Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score | Growth and Development Score | -15.0 score on a scale |
Other Pre-specified
Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers
Time frame: Day 1 up to Taper Period, up to Week 52
Population: Seizure frequency was assessed in participants with available data in the Safety Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tuberous Sclerosis Complex | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Taper Period | 71.90 seizure frequency | — |
| Tuberous Sclerosis Complex | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 86-113 | -95.20 seizure frequency | — |
| Tuberous Sclerosis Complex | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 114-141 | -97.60 seizure frequency | — |
| Tuberous Sclerosis Complex | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 142-169 | -97.80 seizure frequency | — |
| Tuberous Sclerosis Complex | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 170-197 | -88.10 seizure frequency | — |
| Tuberous Sclerosis Complex | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 1-29 | 56.05 seizure frequency | Standard Deviation 26.23 |
| Tuberous Sclerosis Complex | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 30-57 | 24.80 seizure frequency | — |
| Tuberous Sclerosis Complex | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 58-85 | 2.70 seizure frequency | — |
| Dravet Syndrome | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 1-29 | -67.80 seizure frequency | — |
| Dravet Syndrome | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 114-141 | -85.80 seizure frequency | — |
| Dravet Syndrome | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 30-57 | -89.50 seizure frequency | — |
| Dravet Syndrome | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 86-113 | -80.20 seizure frequency | — |
| Dravet Syndrome | Percentage Change From Baseline in Indication-Specific Seizure Frequency As Recorded by Caregivers | Day 58-85 | -94.70 seizure frequency | — |