Adverse events (AEs) were defined as any new unfavorable/unintended signs/symptoms (including abnormal laboratory findings when relevant) or diagnosis or worsening of a pre-existing condition that occurs during the study. TEAEs were defined as the AEs that started or worsened in severity or seriousness following the first dose of GWP42003-P. A serious AE was defined as any AE that results in any of the following outcomes: death, life-threatening adverse experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or cancer, any other experience that suggests a significant hazard, contraindication, side effect or precaution that may require medical or surgical intervention to prevent one of the outcomes listed above, or an event that changes the risk/benefit ratio of the study.

Adverse events were assessed in the Safety Analysis Set.

Treatment-emergent clinical parameters were defined as the following: Treatment-emergent alanine transferase (ALT) > 3×upper limit of normal (ULN), > 5×ULN and > 8×ULN; Treatment-emergent aspartate aminotransferase (AST) > 3×ULN, > 5×ULN and > 8×ULN; Treatment-emergent ALT or AST > 3×ULN, > 5×ULN and > 8×ULN; Treatment-emergent ALT or AST > 3×ULN and either bilirubin > 2×ULN or international normalized ratio (INR) > 1.5.

Clinical laboratory parameters were assessed in the Safety Analysis Set.

Potentially clinically significant vital sign values of blood pressure (BP) were defined as sitting systolic BP (mmHg) change: < -20 or > 20 mmHg and sitting diastolic BP change: < -10 or > 10 mmHg. Vital sign measurements were taken in a sitting position at rest for 5 minutes. Blood pressure readings were recorded using the same arm throughout the trial, when possible.

Vital signs were assessed in participants with available data in the Safety Analysis Set.

Potentially clinically significant vital sign values of pulse rate were defined as pulse rate change: < -10 or > 10 beats per minute. Vital sign measurements were taken in a sitting position at rest for 5 minutes.

Pulse rate was assessed in the Safety Analysis Set.

Clinically significant body weight changes were defined as the percent change in body weight (≤7% change or ≥7% change).

Body weight was assessed in participants with available data in the Safety Analysis Set.

Electrocardiogram assessments were performed for QTcB and QTcF >450 msec, >480 msec, and >500 msec. QTcB = corrected QT interval with Bazette correction. QTcF = QTc corrected by Fridericia.

Electrocardiogram assessments were performed in participants with available data in the Safety Analysis Set.

Participants were evaluated for any changes to typical menstrual cycles, duration of menstrual cycles, and typical strength of the menstrual cycles during the study.

Changes in menstruation cycle was assessed in participants with available data in the Safety Analysis Set.

Suicidal ideation and behavior was assessed by the investigator via a clinical interview with the caregiver. The questionnaire included following questions: Has the child expressed any wish to be dead?, Has the child made any suicide attempts?, Has the child shown any non-suicidal self-injurious behavior? The responses were recorded as Yes/No.

Suicidal ideation or behavior was assessed in participants with available data in the Safety Analysis Set.

Blood samples were collected to assess changes in serum IGF-1 levels. A negative mean change from baseline indicates a reduction in IGF-1 levels.

IGF-1 levels were assessed in participants with available data in the Safety Analysis Set.

Pubic hair growth and breast development of all adolescents were assessed by the investigator or caregiver using Tanner Staging categorization from 1 to 5.

Stage 1- No glandular tissue; areola follows skin contours of chest; No pubic hair Stage 2- Breast bud forms; areola begins to widen; a small amount of long, downy hair with slight pigmentation on labia majora Stage 3- Breast begins to become more elevated and extends beyond borders of the areola, which continues to widen but remains in contour with surrounding breast; Hair becomes more coarse and curly and begins to extend laterally Stage 4- Increased breast size and elevation; areola and papilla form a secondary mound projecting from the contour of the surrounding breast; Adult-like hair quality, extending across pubis but sparing medial thighs Stage 5- Breast reaches final adult size; areola returns to the contour of the surrounding breast, with a projecting central papilla; Hair extends to medial surface of the thigh.

Changes in Tanner staging was assessed in the Safety Analysis Set.

RSBQ is a caregiver-completed questionnaire that assesses the overall condition (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. A negative mean change from baseline indicates an improvement in overall condition.

Rett Syndrome Behaviour Questionnaire (RSBQ) was assessed in the Safety Analysis Set.

CGI-I is a 7-point scale that requires the clinician to assess whether a patient's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was 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. The mean continuous CGI-I score (averaged from each treatment enrolled under protocol and under annex) at Visit 14 (Day 729) is being reported. Higher mean scores indicate worse condition.

Clinical Global Impressions - Improvement was assessed in the Safety Analysis Set.

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 was 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. The mean continuous CGI-S score (averaged from each treatment enrolled under protocol and under annex) at Visit 14 (Day 729) is being reported. Higher scores indicate more severe disease.

Clinician Global Impressions - Severity was assessed in the Safety Analysis Set.

CSHQ is a caregiver-completed sleep screening instrument designed for school-aged children; which includes 33 items within 8 subscales:bedtime resistance (score range 6-18), sleep onset delay (range 1-3), sleep duration (range 3-9), sleep anxiety (range 4-12), night wakings (range 3-9), parasomnias (range 7-21), sleep-disordered breathing (range 3-9), daytime sleepiness (range 8-24). The 33 items 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. A score of 3 indicates greater severity; however, 6 items (1-Goes to bed at same time; 3-Falls asleep in own bed; 26-Wakes by himself; 2-Falls asleep in 20 minutes; 10-Sleeps the right amount; 11-Sleeps same amount each day) are reverse scored. The total summed score ranges from 33 to 99, with higher scores indicating disturbed sleep behavior. A negative mean change from baseline indicates improvement in sleep.

Children's Sleep Habits Questionnaire (CSHQ) was assessed in the Safety Analysis Set.

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 (Regression of motor skills; Poor eye/social contact; Lack of sustained interest; Does not reach for objects or people; Chewing difficulties; Speech disturbance; Hand clumsiness; Dystonia; and 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. A negative mean change from baseline indicates improvement in behavior.

Motor Behavioral Assessment (MBA-9) was assessed in the Safety Analysis Set.