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

Key Inclusion Criteria:

- Patient (if possessing adequate understanding, in the investigator's opinion) and/or
her parent(s)/legal representative is willing and able to give informed consent/assent
for participation in the trial.

- Patient and her 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).

- Patient must weigh at least 9 kg.

- Clinical diagnosis of Rett syndrome (typical or atypical), defined according to
RettSearch Consortium criteria.

- Confirmed genetic mutation of the MECP2 gene.

- Patient must be post-regression (≥ 6 months since last loss of hand use or verbal
language or gross motor regression).

- 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 patient/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).

- Patient 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.

- Patient and/or parent(s)/legal representative is willing to allow the patient's
primary care practitioner (if she has one) and consultant (if she has one) to be
notified of participation in the trial, if the primary care practitioner/consultant is
different to the investigator.

Key Exclusion Criteria:

- Patient 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).

- Patient has clinically significant abnormal laboratory values, in the investigator's
opinion.

- Patient 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 ECG measured at screening or randomization.

- Concurrent cardiovascular conditions which will, in the investigator's opinion,
interfere with the ability to assess her ECGs or put the patient 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. 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.

- Patient has significantly 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.

- Pregnant (positive pregnancy test) or lactating.

- Received an IMP within the 3 months prior to screening.

- Patient 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.

- Patient 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 patient at risk because of participation in the trial, may influence the
result of the trial, or the patient's ability to participate in the trial.

- Any abnormalities identified following a physical examination of the patient that, in
the opinion of the investigator, would jeopardize the safety of the patient if she
took part in the trial.

- Patient has been previously randomized into this trial.

- Patient has travel outside the country of residence planned during the trial.