Efficacy and Safety of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome

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 exclusion criteria for Rett syndrome diagnosis (traumatic brain injury, neurometabolic disease, or severe infection that causes neurological problems; grossly abnormal psychomotor development in the first 6 months of life). * Participant has clinically significant abnormal laboratory values, in the investigator's opinion. * Participant is taking more than 2 concurrent AEDs. * Any history of suicidal behavior or any suicidal ideation in the last month or at screening * Clinically relevant abnormalities in the electrocardiogram (ECG) measured at screening or randomization * Concurrent cardiovascular conditions which will, in the investigator's opinion, interfere with the ability to assess their ECGs or put the participant at risk because of participation in the trial * First or second degree relative with a history of significant ECG abnormalities, in the opinion of the investigator (e.g. premature cardiac arrest, sudden death) * Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP (active or placebo), such as sesame oil * Participant has moderately impaired hepatic function at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × upper limit of normal (ULN) or total bilirubin \> 2 × ULN. * Participant is of childbearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control (e.g., combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner, sexual abstinence) during the trial and for 3 months thereafter. * Pregnant (positive pregnancy test) or lactating * Received an IMP within the 3 months prior to screening * Participant has been taking felbamate for less than 1 year prior to screening. * Currently using or has used recreational or medicinal cannabis, cannabinoid-based medications (including Sativex®), or cannabidiol oral solutions (including CBD-OS \[GWP42003-P\]) within the 3 months prior to screening and is unwilling to abstain for the duration of the trial * Participant has a positive delta-9-tetrahydrocannabinol (THC) test at screening. * Any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory) or significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, may influence the result of the trial, or the participant's ability to participate in the trial * Any abnormalities identified following a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if she took part in the trial * Participant has been previously randomized into this trial. * Participant has traveled outside the country of residence planned during the trial.