Rett Syndrome, RTT
Conditions
Keywords
Cannabidiol, CBD, Epidiolex, GWP42003-P
Brief summary
To evaluate the efficacy of cannabidiol oral solution (GWP42003-P, CBD-OS) in reducing symptom severity when compared with placebo, in participants with Rett syndrome.
Interventions
DRUGGWP42003-P
GWP42003-P presented as an oral solution containing cannabidiol
DRUGPlacebo
Matching placebo oral solution
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participant (if possessing adequate understanding, in the investigator's opinion) and/or their parent(s)/legal representative is willing and able to give informed consent/assent for participation in the trial. * Participant and their caregiver are willing and able (in the investigator's opinion) to comply with all trial requirements (including the completion of all caregiver assessments by the same caregiver throughout the trial). * Participant must weigh at least 10 kilograms. * Clinical diagnosis of Rett syndrome (typical or atypical), defined according to RettSearch Consortium criteria * Confirmed pathogenic genetic mutation of the MECP2 gene * Participant must be post-regression (≥ 6 months since last loss of hand use or verbal language or gross motor regression). * Participant must have a disease severity of between 10 and 36, defined according to the Clinical Severity Scale (CSS). * All medications or interventions (including antiepileptic drugs \[AEDs\] and non-pharmacological interventions - dietary supplements, probiotics, physical therapy, speech therapy, etc.) for Rett syndrome-related symptoms must have been stable for 4 weeks prior to screening and the participant/caregiver must be willing to maintain a stable regimen throughout the trial. * Ability to swallow the investigational medicinal product (IMP) provided as a liquid solution, or the ability for IMP to be delivered via gastrostomy (G) or nasogastric (NG) feeding tube (only G-or NG-tubes made from polyurethane or silicon are allowed) * Participant and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law. * Participant and/or parent(s)/legal representative is willing to allow the participant's primary care practitioner (if they have one) and consultant (if they have one) to be notified of participation in the trial, if the primary care practitioner/consultant is different than the investigator. Key
Exclusion criteria
* Participant meets
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Baseline; Week 24 | RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is not true as far as you know, 1 indicating an item is somewhat or sometimes true, and 2 indicating an item that is very true or often true. Item 31 (Uses eye gaze to convey feelings, needs and wishes) is reverse scored (0 indicating very true or often true, 1 indicating somewhat or sometimes true, and 2 indicating not true as far as you know). The total summed score ranges from 0 to 90, with higher scores representing greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24 | Baseline; Week 24 | CGI-I is a 7-point scale that requires the clinician to assess how much a participant's illness has improved or worsened relative to a Baseline state at the beginning of the intervention. This is rated as: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. |
| Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24 | Baseline; Week 24 | CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment relative to the clinician's experience with participants who had the same diagnosis. This is rated as: 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill. |
| Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Baseline; Week 24 | RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is not true as far as you know, 1 indicating an item is somewhat or sometimes true, and 2 indicating an item that is very true or often true. Item 31 (Uses eye gaze to convey feelings, needs and wishes) is reverse scored (0 indicating very true or often true, 1 indicating somewhat or sometimes true, and 2 indicating not true as far as you know). The total summed score ranges from 0 to 90, with higher scores represent greater severity. |
| Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline; Week 24 | MBA-9 is derived from the full MBA scale (37 Rett syndrome symptoms) by selecting the items deemed amenable to change and which reflected areas of meaningful clinical change. the MBA-9 includes 9 items (1-Regression of motor skills; 2-Poor eye/social contact; 3-Lack of sustained interest; 4-Does not reach for objects or people; 5-Chewing difficulties; 6-Speech disturbance; 7-Hand clumsiness; 8-Dystonia and 9-Hypertonia/rigidity); for each item, the severity of current symptoms is rated by the investigator on a 5-point numerical scale ranging from 0 to 4 with higher scores representing greater severity (0 = normal or never; 1 = mild or rare; 2 = moderate or occasional; 3 = marked or frequent; 4 = very severe or constant). Total MBA-9 score was calculated by summing the scores of 9 different subscale items. The total summed score ranges from 0 to 36, with higher scores representing greater severity. CFB = Change from Baseline. |
| Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline; Week 24 | CSHQ is a caregiver-completed sleep screening instrument designed for school-aged children; which includes 33 items within 8 subscales: 1) bedtime resistance (score range 6-18), 2) sleep onset delay (range 1-3), 3) sleep duration (range 3-9), 4) sleep anxiety (range 4-12), 5) night wakings (range 3-9), 6) parasomnias (range 7-21), 7) sleep-disordered breathing (range 3-9), 8) daytime sleepiness (range 8-24). Item scores range from 1 to 3, where 3=usually (≥5 times/week), 2=sometimes (2-4 times/week), and 1=rarely (≤1 time/week); for items 31 and 32; 3=fall asleep, 2=very sleepy, 1=not sleepy. In general, a score of 3 indicates greater severity, however, 6 items (1-Goes to bed at same time; 2-Falls asleep in 20 minutes; 3-Falls asleep in own bed; 10-Sleeps the right amount; 11-Sleeps same amount each day; 26-Wakes by himself) are reverse scored. Total summed score ranges from 33 to 99, with higher scores representing more disturbed sleep behavior. CFB = Change from Baseline. |
| Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline; Week 24 | RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics in individuals with Rett Syndrome. The 45-item RSBQ is comprised of 8 subscales: 1) general mood (score range 0-16), 2) breathing problems (range 0-10), 3) hand behaviors (range 0-12), 4) face movements (range 0-8), 5) body rocking (BR)/expressionless face (range 0-12), 6) night-time behaviors (range 0-6), 7) anxiety/fear (range 0-8), 8) walking/standing (range 0-4). Each item is rated on a 3-point scale (0-2); 0 indicating an item that is not true as far as you know, 1 indicating an item is somewhat or sometimes true, and 2 indicating an item that is very true or often true. Item 31 (Uses eye gaze to convey feelings, needs and wishes) is reverse scored (0 indicating very true or often true, 1 indicating somewhat or sometimes true, and 2 indicating not true as far as you know). Higher scores representing greater severity. CFB = Change from Baseline. |
Countries
Italy, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 41 participants were screened for eligibility; 29 were randomized to the study treatments, and 12 were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| 5 mg/kg/Day GWP42003-P Participants received 5 milligrams (mg)/kilogram (kg)/day GWP42003-P, administered as 100 mg/milliliter (mL) oral solution twice daily (BID). | 11 |
| 15 mg/kg/Day GWP42003-P Participants received 15 mg/kg/day GWP42003-P, administered as 100 mg/mL oral solution BID. | 9 |
| Placebo Participants received placebo oral solution matched to 5 or 15 mg/kg/day GWP42003-P, BID. | 9 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Physician Decision | 2 | 1 | 3 |
| Overall Study | Sponsor Decision - Covid-19 Precaution | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
| Overall Study | Withdrawal (Covid-19) | 0 | 2 | 0 |
| Overall Study | Withdrawal of Consent Due To Covid-19 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 5 mg/kg/Day GWP42003-P | 15 mg/kg/Day GWP42003-P | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 9 Participants | 9 Participants | 29 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 9.7 years STANDARD_DEVIATION 6.02 | 10.7 years STANDARD_DEVIATION 3.64 | 8.6 years STANDARD_DEVIATION 5.53 | 9.7 years STANDARD_DEVIATION 5.11 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 9 Participants | 9 Participants | 28 Participants |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 9 Participants | 29 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 9 / 11 | 7 / 9 | 7 / 9 |
| serious Total, serious adverse events | 2 / 11 | 2 / 9 | 1 / 9 |
Outcome results
Primary
Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo
RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is not true as far as you know, 1 indicating an item is somewhat or sometimes true, and 2 indicating an item that is very true or often true. Item 31 (Uses eye gaze to convey feelings, needs and wishes) is reverse scored (0 indicating very true or often true, 1 indicating somewhat or sometimes true, and 2 indicating not true as far as you know). The total summed score ranges from 0 to 90, with higher scores representing greater severity.
Time frame: Baseline; Week 24
Population: Intent-to-Treat (ITT) Set: All randomized participants who received at least 1 dose of drug in the trial, and had Baseline efficacy data. Participants with non-missing data were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg/kg/Day GWP42003-P | Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Baseline | 45.9 units on a scale | Standard Deviation 16.77 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Change from Baseline at Week 24 | -12.1 units on a scale | Standard Deviation 13.63 |
| Placebo | Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Change from Baseline at Week 24 | -6.1 units on a scale | Standard Deviation 7.22 |
| Placebo | Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Baseline | 50.0 units on a scale | Standard Deviation 7.56 |
Secondary
Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24
MBA-9 is derived from the full MBA scale (37 Rett syndrome symptoms) by selecting the items deemed amenable to change and which reflected areas of meaningful clinical change. the MBA-9 includes 9 items (1-Regression of motor skills; 2-Poor eye/social contact; 3-Lack of sustained interest; 4-Does not reach for objects or people; 5-Chewing difficulties; 6-Speech disturbance; 7-Hand clumsiness; 8-Dystonia and 9-Hypertonia/rigidity); for each item, the severity of current symptoms is rated by the investigator on a 5-point numerical scale ranging from 0 to 4 with higher scores representing greater severity (0 = normal or never; 1 = mild or rare; 2 = moderate or occasional; 3 = marked or frequent; 4 = very severe or constant). Total MBA-9 score was calculated by summing the scores of 9 different subscale items. The total summed score ranges from 0 to 36, with higher scores representing greater severity. CFB = Change from Baseline.
Time frame: Baseline; Week 24
Population: ITT Set. Participants with non-missing data were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Hand Clumsiness | -0.6 units on a scale | Standard Deviation 1.33 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Dysonia | 1.0 units on a scale | Standard Deviation 1.41 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Lack of Sustained Interest | 1.8 units on a scale | Standard Deviation 0.79 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB MBA-9 Total Score | 0.0 units on a scale | Standard Deviation 4.87 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Dysonia | 0.4 units on a scale | Standard Deviation 1.42 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Hypertonia/Rigidity | 1.4 units on a scale | Standard Deviation 1.51 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline MBA-9 Total Score | 17.2 units on a scale | Standard Deviation 5.81 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Lack of Sustained Interest | 0.0 units on a scale | Standard Deviation 0.71 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Hypertonia/Rigidity | 0.4 units on a scale | Standard Deviation 0.73 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Speech Disturbance | 0.0 units on a scale | Standard Deviation 0 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Chewing Difficulties | 1.3 units on a scale | Standard Deviation 1.34 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Does Not Reach for Objects or People | -0.4 units on a scale | Standard Deviation 2.24 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Does Not Reach for Objects or People | 2.0 units on a scale | Standard Deviation 1.25 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Chewing Difficulties | -0.2 units on a scale | Standard Deviation 0.67 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Poor Eye/Social Contact | 0.0 units on a scale | Standard Deviation 0.87 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Speech Disturbance | 3.0 units on a scale | Standard Deviation 0.47 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Regression of Motor Skills | 0.3 units on a scale | Standard Deviation 1.58 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Poor Eye/Social Contact | 1.7 units on a scale | Standard Deviation 0.82 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Hand Clumsiness | 2.8 units on a scale | Standard Deviation 1.14 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Regression of Motor Skills | 2.2 units on a scale | Standard Deviation 1.23 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Chewing Difficulties | 0.0 units on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Regression of Motor Skills | -0.3 units on a scale | Standard Deviation 0.49 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Poor Eye/Social Contact | 1.6 units on a scale | Standard Deviation 1.01 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Lack of Sustained Interest | -0.3 units on a scale | Standard Deviation 1.11 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Speech Disturbance | 2.8 units on a scale | Standard Deviation 0.83 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Hand Clumsiness | 2.8 units on a scale | Standard Deviation 1.56 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Dysonia | 1.2 units on a scale | Standard Deviation 1.56 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline MBA-9 Total Score | 17.3 units on a scale | Standard Deviation 6.78 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB MBA-9 Total Score | -1.9 units on a scale | Standard Deviation 4.06 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Regression of Motor Skills | 2.6 units on a scale | Standard Deviation 0.88 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Poor Eye/Social Contact | -0.1 units on a scale | Standard Deviation 0.69 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Lack of Sustained Interest | 2.1 units on a scale | Standard Deviation 1.17 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Does Not Reach for Objects or People | 1.9 units on a scale | Standard Deviation 1.05 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Does Not Reach for Objects or People | -0.4 units on a scale | Standard Deviation 0.98 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Chewing Difficulties | 1.3 units on a scale | Standard Deviation 0.5 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Speech Disturbance | 0.0 units on a scale | Standard Deviation 0.58 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Hand Clumsiness | -0.4 units on a scale | Standard Deviation 1.13 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Dysonia | -0.1 units on a scale | Standard Deviation 0.9 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Hypertonia/Rigidity | 1.1 units on a scale | Standard Deviation 1.45 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Hypertonia/Rigidity | -0.1 units on a scale | Standard Deviation 0.38 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Does Not Reach for Objects or People | 0.1 units on a scale | Standard Deviation 1.21 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Hand Clumsiness | 0.0 units on a scale | Standard Deviation 0.58 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB MBA-9 Total Score | 0.0 units on a scale | Standard Deviation 3.92 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Does Not Reach for Objects or People | 2.3 units on a scale | Standard Deviation 1.25 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Dysonia | 0.1 units on a scale | Standard Deviation 1.46 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Chewing Difficulties | 1.1 units on a scale | Standard Deviation 0.74 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Chewing Difficulties | 0.4 units on a scale | Standard Deviation 0.53 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Hypertonia/Rigidity | 1.0 units on a scale | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Lack of Sustained Interest | -0.1 units on a scale | Standard Deviation 0.38 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline MBA-9 Total Score | 16.8 units on a scale | Standard Deviation 5.96 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Dysonia | 1.0 units on a scale | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Hypertonia/Rigidity | 0.0 units on a scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Hand Clumsiness | 3.1 units on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Speech Disturbance | 0.3 units on a scale | Standard Deviation 0.49 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Speech Disturbance | 2.7 units on a scale | Standard Deviation 0.48 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Poor Eye/Social Contact | 1.5 units on a scale | Standard Deviation 0.97 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Regression of Motor Skills | 2.6 units on a scale | Standard Deviation 0.84 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Poor Eye/Social Contact | -0.9 units on a scale | Standard Deviation 1.07 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | CFB Regression of Motor Skills | 0.0 units on a scale | Standard Deviation 0.58 |
| Placebo | Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 | Baseline Lack of Sustained Interest | 1.5 units on a scale | Standard Deviation 0.71 |
Secondary
Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24
CSHQ is a caregiver-completed sleep screening instrument designed for school-aged children; which includes 33 items within 8 subscales: 1) bedtime resistance (score range 6-18), 2) sleep onset delay (range 1-3), 3) sleep duration (range 3-9), 4) sleep anxiety (range 4-12), 5) night wakings (range 3-9), 6) parasomnias (range 7-21), 7) sleep-disordered breathing (range 3-9), 8) daytime sleepiness (range 8-24). Item scores range from 1 to 3, where 3=usually (≥5 times/week), 2=sometimes (2-4 times/week), and 1=rarely (≤1 time/week); for items 31 and 32; 3=fall asleep, 2=very sleepy, 1=not sleepy. In general, a score of 3 indicates greater severity, however, 6 items (1-Goes to bed at same time; 2-Falls asleep in 20 minutes; 3-Falls asleep in own bed; 10-Sleeps the right amount; 11-Sleeps same amount each day; 26-Wakes by himself) are reverse scored. Total summed score ranges from 33 to 99, with higher scores representing more disturbed sleep behavior. CFB = Change from Baseline.
Time frame: Baseline; Week 24
Population: ITT Set. Participants with non-missing data were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Night wakings | 5.3 units on a scale | Standard Deviation 2.36 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep onset delay | 1.5 units on a scale | Standard Deviation 0.71 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Night wakings | -0.4 units on a scale | Standard Deviation 0.88 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Parasomnias | -0.6 units on a scale | Standard Deviation 1.51 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep onset delay | 0.1 units on a scale | Standard Deviation 1.27 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Daytime sleepiness | -0.7 units on a scale | Standard Deviation 3.64 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Parasomnias | 11.0 units on a scale | Standard Deviation 1.49 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep duration | 4.7 units on a scale | Standard Deviation 2.41 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep duration | 0.4 units on a scale | Standard Deviation 1.13 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep anxiety | 5.6 units on a scale | Standard Deviation 1.65 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Total Score | 49.8 units on a scale | Standard Deviation 9.75 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep anxiety | -0.1 units on a scale | Standard Deviation 0.78 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Bedtime resistance | 9.2 units on a scale | Standard Deviation 3.43 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Total score | -1.6 units on a scale | Standard Deviation 6.17 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Daytime sleepiness | 11.6 units on a scale | Standard Deviation 3.2 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep disordered breathing | -0.4 units on a scale | Standard Deviation 1.74 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep disordered breathing | 4.2 units on a scale | Standard Deviation 1.69 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Bedtime resistance | 0.0 units on a scale | Standard Deviation 1 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep disordered breathing | -0.9 units on a scale | Standard Deviation 1.07 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Bedtime resistance | 7.3 units on a scale | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Parasomnias | -1.1 units on a scale | Standard Deviation 1.68 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Daytime sleepiness | -1.4 units on a scale | Standard Deviation 2.07 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Total Score | 46.7 units on a scale | Standard Deviation 4.9 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Total score | -5.0 units on a scale | Standard Deviation 6.14 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Bedtime resistance | -0.4 units on a scale | Standard Deviation 1.27 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep onset delay | 1.4 units on a scale | Standard Deviation 0.53 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep onset delay | -0.1 units on a scale | Standard Deviation 0.69 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep duration | 3.4 units on a scale | Standard Deviation 0.73 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep duration | -0.3 units on a scale | Standard Deviation 0.95 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep anxiety | 4.6 units on a scale | Standard Deviation 0.73 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep anxiety | -0.1 units on a scale | Standard Deviation 0.38 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Night wakings | 4.4 units on a scale | Standard Deviation 1.33 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Night wakings | -0.6 units on a scale | Standard Deviation 1.4 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Parasomnias | 10.4 units on a scale | Standard Deviation 1.42 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep disordered breathing | 4.0 units on a scale | Standard Deviation 1.22 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Daytime sleepiness | 13.2 units on a scale | Standard Deviation 2.39 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Daytime sleepiness | -1.3 units on a scale | Standard Deviation 2.56 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Night wakings | 0.1 units on a scale | Standard Deviation 0.69 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep onset delay | -0.6 units on a scale | Standard Deviation 0.53 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Daytime sleepiness | 13.7 units on a scale | Standard Deviation 2.5 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Parasomnias | 11.7 units on a scale | Standard Deviation 2.63 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep onset delay | 1.8 units on a scale | Standard Deviation 0.79 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Parasomnias | -1.4 units on a scale | Standard Deviation 2.3 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Bedtime resistance | 7.0 units on a scale | Standard Deviation 1.25 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Bedtime resistance | -0.1 units on a scale | Standard Deviation 1.68 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep disordered breathing | 3.7 units on a scale | Standard Deviation 1.06 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Total score | -3.7 units on a scale | Standard Deviation 4.07 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep duration | -0.4 units on a scale | Standard Deviation 1.72 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep duration | 4.5 units on a scale | Standard Deviation 1.58 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Total Score | 49.4 units on a scale | Standard Deviation 5.42 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Sleep anxiety | 4.9 units on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep disordered breathing | -0.1 units on a scale | Standard Deviation 0.38 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | CFB Sleep anxiety | 0.0 units on a scale | Standard Deviation 1.15 |
| Placebo | Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 | Baseline Night wakings | 4.6 units on a scale | Standard Deviation 1.43 |
Secondary
Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24
CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment relative to the clinician's experience with participants who had the same diagnosis. This is rated as: 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill.
Time frame: Baseline; Week 24
Population: ITT Set. Participants with non-missing data were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24 | Baseline | 4.3 units on a scale | Standard Deviation 1.25 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24 | Change from Baseline at Week 24 | -0.1 units on a scale | Standard Deviation 0.33 |
| Placebo | Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24 | Baseline | 4.2 units on a scale | Standard Deviation 0.67 |
| Placebo | Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24 | Change from Baseline at Week 24 | -0.1 units on a scale | Standard Deviation 0.38 |
| Placebo | Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24 | Baseline | 4.4 units on a scale | Standard Deviation 0.84 |
| Placebo | Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24 | Change from Baseline at Week 24 | 0.0 units on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in Mean RSBQ Subscale Scores at Week 24
RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics in individuals with Rett Syndrome. The 45-item RSBQ is comprised of 8 subscales: 1) general mood (score range 0-16), 2) breathing problems (range 0-10), 3) hand behaviors (range 0-12), 4) face movements (range 0-8), 5) body rocking (BR)/expressionless face (range 0-12), 6) night-time behaviors (range 0-6), 7) anxiety/fear (range 0-8), 8) walking/standing (range 0-4). Each item is rated on a 3-point scale (0-2); 0 indicating an item that is not true as far as you know, 1 indicating an item is somewhat or sometimes true, and 2 indicating an item that is very true or often true. Item 31 (Uses eye gaze to convey feelings, needs and wishes) is reverse scored (0 indicating very true or often true, 1 indicating somewhat or sometimes true, and 2 indicating not true as far as you know). Higher scores representing greater severity. CFB = Change from Baseline.
Time frame: Baseline; Week 24
Population: ITT Set. Participants with non-missing data were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Night-time Behaviors Score | 0.8 units on a scale | Standard Deviation 1.14 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Hand Behaviors Score | 7.8 units on a scale | Standard Deviation 2.15 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Breathing Problems Score | 0.2 units on a scale | Standard Deviation 1.86 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Walking/Standing Score | 0.9 units on a scale | Standard Deviation 2.09 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline General Mood Score | 6.0 units on a scale | Standard Deviation 3.65 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Anxiety/Fear Score | -0.2 units on a scale | Standard Deviation 1.92 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Breathing Problems Score | 4.7 units on a scale | Standard Deviation 2.45 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB General Mood Score | -0.6 units on a scale | Standard Deviation 2.7 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Hand Behaviors Score | 0.7 units on a scale | Standard Deviation 2.24 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Face Movements Score | 2.3 units on a scale | Standard Deviation 2.45 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Walking/Standing Score | 2.7 units on a scale | Standard Deviation 1.64 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Anxiety/Fear Score | 4.0 units on a scale | Standard Deviation 1.89 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Night-time Behaviors Score | 0.2 units on a scale | Standard Deviation 0.97 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Body Rocking/Expressionless Face Score | 4.5 units on a scale | Standard Deviation 2.59 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Body Rocking/Expressionless Face Score | 0.6 units on a scale | Standard Deviation 2.46 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Face Movements Score | 0.0 units on a scale | Standard Deviation 1.12 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB General Mood Score | -4.9 units on a scale | Standard Deviation 2.67 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Breathing Problems Score | 5.0 units on a scale | Standard Deviation 3.08 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Breathing Problems Score | -1.0 units on a scale | Standard Deviation 1.53 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Hand Behaviors Score | 7.6 units on a scale | Standard Deviation 3.54 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Face Movements Score | 4.6 units on a scale | Standard Deviation 2.13 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Night-time Behaviors Score | -0.1 units on a scale | Standard Deviation 1.46 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Walking/Standing Score | 0.0 units on a scale | Standard Deviation 0.58 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline General Mood Score | 8.2 units on a scale | Standard Deviation 4.58 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Hand Behaviors Score | -0.9 units on a scale | Standard Deviation 3.29 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Face Movements Score | -1.4 units on a scale | Standard Deviation 1.72 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Body Rocking/Expressionless Face Score | 5.1 units on a scale | Standard Deviation 1.96 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Body Rocking/Expressionless Face Score | -0.6 units on a scale | Standard Deviation 1.13 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Night-time Behaviors Score | 0.8 units on a scale | Standard Deviation 0.97 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Anxiety/Fear Score | 4.6 units on a scale | Standard Deviation 2.46 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Anxiety/Fear Score | -1.3 units on a scale | Standard Deviation 2.29 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Walking/Standing Score | 2.1 units on a scale | Standard Deviation 1.36 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Body Rocking/Expressionless Face Score | 5.4 units on a scale | Standard Deviation 2.59 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Breathing Problems Score | -0.3 units on a scale | Standard Deviation 1.25 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Walking/Standing Score | 0.1 units on a scale | Standard Deviation 1.07 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Night-time Behaviors Score | 1.8 units on a scale | Standard Deviation 1.69 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Face Movements Score | -0.1 units on a scale | Standard Deviation 1.07 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Night-time Behaviors Score | -0.3 units on a scale | Standard Deviation 1.11 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Face Movements Score | 4.3 units on a scale | Standard Deviation 2.21 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Walking/Standing Score | 2.9 units on a scale | Standard Deviation 1.29 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline General Mood Score | 8.9 units on a scale | Standard Deviation 3.14 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Breathing Problems Score | 5.0 units on a scale | Standard Deviation 3.43 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Anxiety/Fear Score | -1.7 units on a scale | Standard Deviation 0.95 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Anxiety/Fear Score | 5.1 units on a scale | Standard Deviation 1.45 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Hand Behaviors Score | 0.1 units on a scale | Standard Deviation 0.9 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB Body Rocking/Expressionless Face Score | -0.1 units on a scale | Standard Deviation 1.86 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | Baseline Hand Behaviors Score | 9.1 units on a scale | Standard Deviation 2.08 |
| Placebo | Change From Baseline in Mean RSBQ Subscale Scores at Week 24 | CFB General Mood Score | -2.6 units on a scale | Standard Deviation 2.57 |
Secondary
Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo
RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is not true as far as you know, 1 indicating an item is somewhat or sometimes true, and 2 indicating an item that is very true or often true. Item 31 (Uses eye gaze to convey feelings, needs and wishes) is reverse scored (0 indicating very true or often true, 1 indicating somewhat or sometimes true, and 2 indicating not true as far as you know). The total summed score ranges from 0 to 90, with higher scores represent greater severity.
Time frame: Baseline; Week 24
Population: ITT Set. Participants with non-missing data were included for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg/kg/Day GWP42003-P | Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Baseline | 39.8 units on a scale | Standard Deviation 12.8 |
| 15 mg/kg/Day GWP42003-P | Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Change from Baseline at Week 24 | 0.4 units on a scale | Standard Deviation 12.51 |
| Placebo | Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Baseline | 50.0 units on a scale | Standard Deviation 7.56 |
| Placebo | Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo | Change from Baseline at Week 24 | -6.1 units on a scale | Standard Deviation 7.22 |
Secondary
Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24
CGI-I is a 7-point scale that requires the clinician to assess how much a participant's illness has improved or worsened relative to a Baseline state at the beginning of the intervention. This is rated as: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse.
Time frame: Baseline; Week 24
Population: ITT Set. Participants with non-missing data were included for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 mg/kg/Day GWP42003-P | Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24 | 3.2 units on a scale | Standard Deviation 1.2 |
| Placebo | Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24 | 2.9 units on a scale | Standard Deviation 1.07 |
| Placebo | Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24 | 3.1 units on a scale | Standard Deviation 0.38 |