Clinical trial NCT04421456
Conditions: Schizophrenia
Keywords: GWP42003-P adjunctive therapy inadequate response to ongoing antipsychotic treatment
Sponsor: Jazz Pharmaceuticals
Start date: 2020-08-18; Completion date: 2022-03-16
Enrollment: 95 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will be conducted to evaluate the efficacy, safety, and tolerability of GWP42003-P versus placebo in participants with schizophrenia experiencing inadequate response to ongoing antipsychotic treatment.

Detailed description:

Arms: arm 1: GWP42003-P 300 milligrams (mg) per day arm 2: Matching placebo arm 3: GWP42003-P 1000 mg per day
Interventions: intervention 1: GWP42003-P intervention 2: Placebo
Intervention descriptions: intervention 1: oral solution containing 100 milligrams per milliliter (mg/mL) cannabidiol (CBD) dissolved in the excipients sesame oil and anhydrous ethanol (10% v/v), with sweetener (sucralose), and strawberry flavoring intervention 2: oral solution containing the excipients sesame oil and anhydrous ethanol, with added β-carotene, sweetener (sucralose), and strawberry flavoring

Protocol documents:
Prot_000.pdf: 
SPONSOR: GW RESEARCH LIMITED
Study Code: GWAP19030
EudraCT Number: 2019-003369-16
Clinical Protocol Global V3, 23Mar2021
Confidential
Page 1 of 104
Clinical Protocol Template (Phase 2–4)
V1, 24Sep15
Clinical Protocol Global V2 Based on Clinical Protocol V1 11Nov2019
A Randomized, Double-blind, Parallel-group Trial to Investigate the 
Safety and Efficacy of GWP42003-P Versus Placebo as Adjunctive 
Therapy in Participants with Schizophrenia Experiencing
Inadequate Response to Ongoing Antipsychotic Treatment
Study Code: GWAP19030
EudraCT Number: 2019-003369-16
CLINICAL PROTOCOL GLOBAL VERSION 3
GW Research Ltd
Sovereign House
Vision Park
Chivers Way
Histon
Cambridge CB24 9BZ
United Kingdom
Tel: +44 (0) 1223 266 800
Fax: +44 (0) 1223 235 667
Confidentiality Statement
This document contains confidential information of GW Research Ltd (GW) that 
must not be disclosed to anyone other than the recipient trial staff and members of the 
institutional review board or independent ethics committee. This information cannot 
be used for any purpose other than the evaluation or conduct of the clinical 
investigation without the prior written consent of GW.


SPONSOR: GW RESEARCH LIMITED
Study Code: GWAP19030
EudraCT Number: 2019-003369-16
Clinical Protocol Global V3, 23Mar2021
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Investigator Agreement
I have read the attached clinical protocol entitled “A Randomized, Double-blind, 
Parallel-group Trial to Investigate the Safety and Efficacy of GWP42003-P Versus 
Placebo as Adjunctive Therapy in Participants with Schizophrenia Experiencing
Inadequate Response to Ongoing Antipsychotic Treatment”, dated 23 March 2021
and agree to abide by all provisions set forth therein.
I agree to comply with applicable regulatory requirement(s); the United States (US)
Food and Drug Administration (FDA) regulations relating to good clinical practice 
(GCP) and clinical trials, the European Union (EU) Clinical Trials Directive
(2001/20/EC), the EU Good Clinical Practice / GCP Directive (2005/28/EC) and 
subsequent applicable regulatory/statutory instruments, or the International Council 
for Harmonisation (ICH) Harmonised Guideline: Integrated Addendum to ICH 
E6(R1): Guideline for GCP E6(R2) where the EU Clinical Trials and GCP Directives
do not apply, and to complete Form FDA 1572, if required. I accept responsibility for 
the overall medical care of participants during the trial and for trial-related medical 
decisions.
I am not aware that any conflicts of interest, financial or otherwise, exist for myself, 
my spouse [or legal partner] and dependent children and agree to confirm this in 
writing if required and update as necessary.
I agree to ensure that the confidential information contained in this document will not 
be used for any purpose other than the evaluation or conduct of the clinical 
investigation without the prior written consent of GW.
Site No:
Print name:
Date:
Principal Investigator
(DD Month YYYY)
Signature:
GW Authorization
Print name:
Date:
VP of Clinical Sciences (Designee)
(DD Month YYYY)
Signature:
	


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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1 
PROTOCOL SYNOPSIS 
Trial Title 
A Randomized, Double-blind, Parallel-group Trial to Investigate 
the Safety and Efficacy of GWP42003-P Versus Placebo as 
Adjunctive Therapy in Participants with Schizophrenia 
Experiencing Inadequate Response to Ongoing Antipsychotic 
Treatment 
Clinical Trial 
Type 
Phase 2b 
Indication 
Participants with schizophrenia experiencing an inadequate 
response to ongoing antipsychotic treatment. 
Objectives / 
Endpoints 
Objective  
Endpoint  
Efficacy  
x To evaluate the 
efficacy of 
GWP42003-P versus 
placebo after 12 weeks 
of treatment 
x Mean change from baseline to Week 12 
in the following: 
 Positive and Negative Symptoms 
Scale (PANSS) total (PANSS-T) 
score 
 PANSS positive subscale 
(PANSS-P) score 
 PANSS negative subscale 
(PANSS-N) score 
 PANSS general subscale 
(PANSS-G) score 
 Clinical Global Impression of 
Severity (CGI-S) score 
x Score at Week 12 in the Clinical Global 
Impression of Improvement (CGI-I) 
Safety 
x To evaluate the safety 
and tolerability of 
GWP42003-P  
x Changes in body weight, body mass 
index (BMI), and waist circumference 
x Changes in vital sign measurements 
x Adverse events (AEs) and adverse drug 
reactions (ADRs) 
 
 
 
x Clinical laboratory test results 
x 12-lead electrocardiogram (ECG) 
parameters 
 
 
Objective  
Endpoint  
P
I
P
I


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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Safety Continued 
 
x Suicidality as assessed by the 
Columbia-Suicide Severity Rating 
Scale (C-SSRS)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Objective 
Endpoint 
P
I
PI


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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Exploratory Continued 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Trial Design 
This is a randomized, double-blind, placebo-controlled, 
parallel-group, outpatient trial. The trial will compare the efficacy 
and safety of 2 dose levels of GWP42003-P (150 mg twice daily 
[b.i.d.] and 500 mg b.i.d.) versus placebo in participants with 
schizophrenia who are experiencing an inadequate response to 
ongoing antipsychotic treatment. 
The duration of the trial will be approximately 20 weeks, which 
includes a screening period (up to 4 weeks), a single-blind placebo 
run-in period (2 weeks), a double-blind treatment period 
(12 weeks), and a safety follow-up period (2 weeks). 
After signing the informed consent form (ICF), participants will 
enter the screening period (Visit 1). The investigator will submit 
participants’ eligibility forms for clinical surveillance and training 
(CST) review. The CST will evaluate the eligibility of participants 
and provide the outcome of the evaluation to the site. Participants 
cannot be enrolled until site personnel have received the final CST 
notification. Additional details for CST will be described in the 
study manual. At Visit 2 screened participants who continue to 
meet eligibility criteria will be randomized 1:1 to receive 150 mg 
b.i.d. or 500 mg b.i.d. dose-matched volumes of placebo in a 
single-blind manner for the placebo run-in period. At Visit 3 
(Day 1) participants who continue to meet the required eligibility 
criteria will be randomized 2:1 to receive GWP42003-P or placebo 
of equivalent volume to their placebo run-in allocation (see table 
below) in a double-blind manner for the treatment period. 
 
P
I


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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Single-blind Allocation 
(Run-in Period) 
Double-blind Allocation 
(Treatment Period) 
150 mg b.i.d. placebo 
150 mg b.i.d. GWP42003-P 
150 mg b.i.d. placebo 
500 mg b.i.d. placebo 
500 mg b.i.d. GWP42003-P 
500 mg b.i.d. placebo 
Randomization will be stratified by region (North America, 
Europe) and by sex (male, female). 
A safety follow-up visit will be conducted 2 weeks after the last 
dose of investigational medicinal product (IMP). If a participant 
discontinues IMP prematurely (i.e., before the end of the treatment 
period) they are required to attend an end of treatment (EOT) visit 
(±3 days) and complete the safety follow-up visit 2 weeks after 
their last dose. Participants are encouraged to attend any 
outstanding visits per the trial schema. If a participant prematurely 
discontinues IMP and withdraws from the trial without continuing 
trial visits as per the trial schema, they are required to attend an 
early termination (ET) visit upon withdrawal and complete the 
safety follow-up visit 2 weeks after their last dose. 
Sample Size 
Approximately 366 participants will be randomized following the 
placebo run-in to receive 1 of 2 dose levels of GWP42003-P 
(150 mg b.i.d. or 500 mg b.i.d.) or dose matching volume of 
placebo (150 mg b.i.d. or 500 mg b.i.d.) on a 2:2:1:1 basis. The 
placebo groups will be pooled for the analyses of efficacy. 
Assuming a common standard deviation of 11.0 and using a 
2-sided hypothesis test at a 0.05 α-level, a total sample size of 
366 participants (122 participants per active dose group and 
61 participants per placebo group) will provide 80% power to 
detect a significant result assuming a true treatment difference of 
−4.32 points on the PANSS-T score in change from baseline to 
EOT between 500 mg b.i.d. of GWP42003-P and placebo. This 
allows for a 15% drop-out rate, with a minimum of 309 participants 
needed to complete the trial. Depending on the drop-out rate, 
during the trial, the number of randomized participants may be 
increased to ensure a minimum of 309 evaluable participants at 
Week 12. 
At least 366 participants will be randomized to receive dose 
matching volume of placebo during the placebo run-in period 
(150 mg b.i.d. and 500 mg b.i.d. in a 1:1 ratio), thereafter 
randomized to receive GWP42003-P (150 mg b.i.d. or 500 mg 
b.i.d.) or dose matching volumes of placebo at a 2:1 ratio within 
each dose level. 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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Summary of 
Participant 
Eligibility 
Criteria 
Inclusion Criteria 
For inclusion in the trial, the participant must fulfill ALL of the 
following criteria: 
x Male or female 18 to 55 years of age at the time of signing the 
ICF. 
x Willing and able to give informed consent for participation in 
the trial. 
x BMI of 18 to 40 kg/m2 inclusive and a body weight ≥ 50 kg at 
screening. 
x Diagnostic and Statistical Manual of Mental Disorders 
(DSM-5) diagnosis of schizophrenia, confirmed by the 
Mini-International Neuropsychiatric Interview (MINI) for 
Psychotic Disorders Studies. 
x Clinically stable outpatient, based on the investigator’s 
judgment and defined by no signs of exacerbation of 
schizophrenia (no hospital admissions or prison incarcerations), 
and no evidence of an increased level of psychiatric care 
(including cognitive behavior rehabilitation or individual 
psychotherapy) within 12 weeks prior to screening. 
x PANSS-T score of ≥ 60 and < 110 at screening and baseline 
visits. 
x Score of ≥ 4 for at least 2 of the following PANSS items: 
delusions (P1), conceptual disorganization (P2), hallucinatory 
behavior (P3), suspiciousness (P6), somatic concern (G1), or 
unusual thought content (G9) at screening visit. 
x Score ≥ 4 (at least moderately ill) on the CGI-S at screening 
visit. 
x Undergoing treatment with at least 1 antipsychotic medication 
with no change in dosing, supported by documentation 
(including pharmacy records), for at least 8 weeks prior to 
screening and no change in antipsychotic medication dosing 
planned throughout the trial. 
x Taking a maximum of 2 antipsychotic medications. For 
participants taking oral antipsychotic medications only, the sum 
of primary and secondary antipsychotic medications is 
≤ 30 mg/day of oral olanzapine equivalents. For participants 
taking long-acting injectable antipsychotic medications, the 
dose is within the range approved and any secondary oral 
antipsychotic medications is ≤ 5 mg/day of oral olanzapine 
equivalents. 
x Documented response (at least partially) to treatment with 
current antipsychotic medications (e.g., treatment of recent 
exacerbation of psychotic symptoms) as assessed by the 


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Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
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investigator or treating physician. Documentation can include 
medical records, pharmacy records, or corroboration in writing 
by the clinician(s) currently responsible for the participant’s 
psychiatric treatment. 
x On a stable dose if taking concomitant psychotropic 
medications and within allowed limits, including 
antidepressants, anxiolytics, anticholinergics and/or 
antiepileptics for at least 4 weeks prior to screening (dose 
reductions ≤ 25% of total dose are permitted) with no plans to 
change dosing during the trial (i.e., from screening onwards). 
Valproic acid or any prescribed valproate product (valproate 
semisodium or valproate sodium) is disallowed within 4 weeks 
(i.e., more than 5 half-lives) prior to the baseline visit. 
x Willing to allow the responsible authorities to be notified of 
participation in the trial, if mandated by local law. 
Exclusion Criteria 
The participant may not enter the trial if ANY of the following 
apply: 
Diagnosis and Psychiatric History 
x Recent (within the last 3 months prior to screening) diagnosis 
of panic disorder, depressive episode, or other comorbid 
psychiatric conditions based on the MINI for Psychotic 
Disorders Studies (or DSM-5) OR has PANSS item G6 score 
of ≥ 5 (depression) at screening. 
x Any psychiatric disorder that may interfere with the conduct of 
this trial, including but not limited to attention deficit 
hyperactivity disorder, pervasive developmental disorder, 
intellectual disability, personality disorder that might interfere 
with compliance or increase suicidal risk, manic or hypomanic 
episode, or any other psychotic disorder, as defined in the 
DSM-5. 
x Current diagnosis or a history of substance use disorder 
according to DSM-5 criteria within 6 months prior to screening 
or prior chronic substance abuse judged likely to recur during 
the trial period by the investigator. Nicotine use or occasional 
cannabis use (≤ 3 days per week recreational cannabis use) is 
acceptable. Corroboration of the participant’s frequency of 
cannabis use by an adult informant (e.g., family member, social 
worker, caseworker, residential facility staff, or nurse), should 
be obtained if the participant has a positive urine test for 
Δ9-tetrahydrocannabinol at screening. 
x A positive drug screen for opiates, methadone, cocaine, 
amphetamines (including ecstasy), or barbiturates; a repeat drug 
screen may be done to verify the result. 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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x Any history of suicidal behavior or any suicidal ideation of 
type 4 or 5 on the adult C-SSRS or within 1 month prior to 
screening. 
x A ± ≥ 20% change in PANSS-T score during the placebo run-in 
period (Visit 2 to Visit 3). 
Treatment History 
x Treatment-resistant schizophrenia as judged by the treating 
physician and as defined by having previously demonstrated no 
response to > 2 trials of antipsychotic trial medications at 
therapeutic doses or required clozapine therapy due to 
non-response to antipsychotic therapy within the previous 
6 months. 
x Non-compliance, as assessed by antipsychotic medication and 
the IMP adherence monitoring Platform: 
 ≤ 75% compliance of current oral antipsychotic medication 
during the single-blind, placebo run-in period (Visit 2 to 
Visit 3). 
 ≤ 75% compliance of current long-acting injectable 
antipsychotic medication as assessed by number of 
administrations falling more than 1 week outside of the 
scheduled due date of administration, in the 6 months prior 
to screening (Visit 1) and baseline (Visit 3). 
 ≤ 75% compliance of IMP during the single-blind, placebo 
run-in period (Visit 2 to Visit 3). 
x Based on the investigator assessment: 
 current antipsychotic medication blood levels are below the 
therapeutic range if therapeutic drug monitoring is available 
for the antipsychotic(s) prescribed for the participant; or 
 there is no documentation confirming the administration of 
long-acting injectable antipsychotic medication within the 
approved dose range and as prescribed by the treating 
physician. 
Past and Current Medical History 
x History of moderate or severe head trauma (for example, loss of 
consciousness for more than 15 minutes) or other neurological 
disorders (including epilepsy), neurodegenerative disorder 
(Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, 
Huntington’s disease, etc.) or systemic medical diseases that 
are, in the opinion of the investigator, likely to interfere with 
the conduct of the trial or confound the trial assessments. 
x Tardive dyskinesia (TD) that is moderate to severe (i.e., a score 
of > 21 on the dyskinesia subscale of the ESRS at screening) or 
requires treatment. 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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x Any other significant disease, disorder, pending court 
proceedings or social circumstances (e.g., homelessness) which, 
in the opinion of the investigator, may either put the participant, 
other participants, or site staff at risk because of participation in 
the trial, may influence the result of the trial, or may affect the 
participant’s ability to take part in the trial. 
Other 
x Any known or suspected hypersensitivity to cannabinoids or 
any of the excipients of the IMP, such as sesame seed oil. 
x One or more laboratory values outside the normal range, based 
on the blood or urine samples taken at the screening visit, that 
are considered by the investigator to be clinically significant; or 
impaired hepatic function at screening, defined as serum 
alanine aminotransferase (ALT) or aspartate aminotransferase 
(AST) > 2 × upper limit of normal (ULN) or total bilirubin 
(TBL) > 1.5 × ULN or international normalized ratio (INR) 
> 1.2 (TBL ULN parameter not applicable for participants 
diagnosed with Gilbert’s disease). Note: Out-of-range 
laboratory values should be confirmed on retest within the 
allowed screening window. 
x Clinically relevant abnormalities in the ECG measured at 
screening or randomization (including QT interval with 
Fridericia correction [QTcF] > 450 msec for males and 
> 470 msec for females, average of 3 measurements). 
x Positive serology panel (including hepatitis B surface antigen 
[HBsAg] and/or confirmed current hepatitis C infection 
[positive hepatitis C virus {HCV} antibody confirmed with 
reflex HCV RNA test]) and/or positive human 
immunodeficiency virus (HIV) antibody/p24 antigen screens. 
x Male and fertile (i.e., after puberty unless permanently sterile 
by bilateral orchidectomy) and with a partner of childbearing 
potential unless agree to ensure that they use male 
contraception (e.g., condom) or remain sexually abstinent 
during the trial and for 3 months after the last dose. 
x Female of childbearing potential (i.e., following menarche until 
becoming postmenopausal for ≥ 12 consecutive months unless 
permanently sterile by hysterectomy, bilateral salpingectomy, 
or bilateral oophorectomy) unless agree to use highly effective 
contraception (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 [provided partner is the sole sexual 


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Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
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partner and has received medical assessment of the surgical 
success], true sexual abstinence) during the trial (i.e., from 
screening) and for 3 months after the last dose. 
x Female who is pregnant (positive pregnancy test), lactating, or 
planning pregnancy during the trial or within 12 weeks after the 
last dose. 
x Received an IMP within 12 weeks prior to the screening visit. 
x Donated blood within 12 weeks prior to the screening visit and 
is unwilling to abstain from donation of blood during the trial. 
x Previously randomized into the placebo run-in period of this 
trial. 
x Travel outside the country of residence planned during the trial, 
unless the participant has confirmation that the IMP is 
permitted in the destination country. 
x Currently using or within 3 months of screening has used CBD 
oil or purified CBD preparations and is unwilling to abstain for 
the duration of the trial. 
Criteria for 
Withdrawal/ 
Discontinuation 
of 
Investigational 
Medicinal 
Product 
The participant must be permanently discontinued from IMP if any 
of the following apply: 
x Administrative decision by the investigator, GW, or regulatory 
authority. 
x Withdrawal of participant consent. 
x Lost to follow-up. 
x Pregnancy. 
x QTcF ≥ 500 msec (average of 3 measurements). 
x Suicidal ideation or behavior of type 4 or 5 during the treatment 
period, as evaluated with the adult C-SSRS or based on 
investigator assessment. 
x Protocol deviation that is considered to potentially compromise 
the safety of the participant or validity of the data collected. 
x ALT or AST > 3 u ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (> 5%). 
x ALT or AST > 8 u ULN. 
x ALT or AST > 5 u ULN for more than 2 weeks. 
x ALT or AST > 3 u ULN and (TBL > 2 u ULN or INR > 1.5). 
Note: Prior to treatment discontinuation for the transaminase 
elevations noted above, the investigator may choose to confirm 
the transaminase elevations by repeating the following 
laboratory tests within 24 to 48 hours: ALT, AST, TBL, INR, 
% eosinophils, gamma-glutamyl transferase, and alkaline 


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phosphatase. Should the above transaminase elevation 
criteria be confirmed, the participant must permanently 
discontinue the IMP. In cases where transaminase elevation 
IMP discontinuation criteria are not met or confirmed, the 
dose of a concomitant medication with known 
hepatotoxicity may be reduced.  
Investigational 
Medicinal 
Product: 
Formulation, 
Mode of 
Administration, 
Dose and 
Regimen 
GWP42003-P oral solution contains 100 mg/mL CBD dissolved in 
the excipients sesame oil and anhydrous ethanol (10% v/v), with 
sweetener (sucralose), and strawberry flavoring. 
Placebo oral solution contains the excipients sesame oil and 
anhydrous ethanol, with added β-carotene, sweetener (sucralose), 
and strawberry flavoring. 
IMP is to be taken orally b.i.d., (e.g., morning and evening), 
preferably within 30 minutes of a meal using the syringe(s) 
provided. The dose should be swallowed. 
Control Group Matching placebo. 
Procedures 
All non-PK visits should be scheduled to take place at 
approximately the same time of day (i.e., morning or afternoon), 
whenever possible. Participants will be requested to abstain from 
recreational cannabis, alcohol, and benzodiazepines for 24 hours 
prior to all trial visits. 
PK Assessments: 
Blood sampling for PK assessments will be conducted during the 
screening period and the treatment period as detailed in the table 
below. 
PK visits will be scheduled in the morning for the participant to 
attend prior to their morning dose of IMP. The time of the 300 kcal 
meal consumed at site by the participant during PK testing days 
will be recorded, as will the dose and dosing time of antipsychotic 
medications/IMP (as appropriate) relative to sampling times. 
Analytes 
Sample Time 
(relative to morning IMP dose) 
Visit 
1 
Visit 
4 
Visit 
7 
Oral 
antipsychotic 
medications 
Predose 
X 
X 
X 
CBD 
7-OH-CBD 
7-COOH-CBD 
Predose 
X 
X 
X 
2 to 3 hours postdose 
 
X 
X 
4 to 6 hours postdose (optional) 
 
X 
X 
8 to 10 hours postdose (optional) 
 
X 
X 


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Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
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Treatment Period Assessments: 
Following the placebo run-in period, participants who continue to 
satisfy all inclusion criteria and none of the exclusion criteria, who 
did not have a ± ≥ 20% change in PANSS-T will be randomized to 
either GWP42003-P or placebo (150 mg b.i.d. or 500 mg b.i.d. or 
volume equivalent). The following assessments will be performed: 
eligibility criteria (recheck if required), physical examination, body 
weight, BMI, waist circumference, vital signs, ECG, previous and 
concomitant medications recorded, and AEs will be reviewed. The 
investigator will complete the ESRS, C-SSRS, PANSS, CGI-S, 
CGI-I, and CDSS. The participant will complete the cannabis use 
survey, PGIC, BACS, SQLS, BAS-MPsQ, and Expectation Module 
of Multidimensional Psychological Questionnaire (EXP-MPsQ). 
Clinical laboratory samples including chemistry, hematology, PK, 
biomarker sampling, urinalysis, drug screen, pregnancy test (for 
WOCBP), and optional pharmacogenomic DNA and RNA 
sampling will be taken. IMP will be dispensed.  
Follow-up Period Assessments: 
Previous and concomitant medications and AEs will be recorded by 
a telephone call. 
PI


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EudraCT Number: 2019-003369-16 
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Statistical 
Considerations 
Statistical hypothesis testing will be performed on the efficacy and 
exploratory endpoints as appropriate. No formal adjustment of 
statistical significance for multiple testing on multiple endpoints 
will be performed, although such multiplicity should be allowed for 
when interpreting the results. 
All safety data will be summarized using appropriate statistical 
methods. 
Sponsor 
GW Research Ltd 
Sovereign House 
Vision Park 
Chivers Way 
Histon 
Cambridge CB24 9BZ 
United Kingdom 
 


SPONSOR: GW RESEARCH LIMITED
Study Code: GWAP19030
EudraCT Number: 2019-003369-16
Clinical Protocol Global V3, 23Mar2021
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Figure 1-1 
Trial Design and Treatment Schematic
b.i.d. = twice daily; EOT = end of treatment; ET = early termination.
g
g


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Table of Contents 
Title Page .................................................................................................. 1 
Investigator Agreement ............................................................................ 2 
1 
PROTOCOL SYNOPSIS ................................................................ 3 
Table of Contents .................................................................................... 16 
List of Appendices................................................................................... 21 
List of In-text Tables .............................................................................. 22 
List of In-text Figures ............................................................................. 23 
List of Abbreviations .............................................................................. 24 
Definition of Terms ................................................................................. 27 
2 
OBJECTIVES/ENDPOINTS ....................................................... 28 
3 
BACKGROUND AND RATIONALE ......................................... 30 
3.1 
Disease......................................................................................................... 30 
3.2 
Investigational Medicinal Product Background .......................................... 31 
3.3 
Rationale ...................................................................................................... 33 
3.4 
Clinical Hypothesis ..................................................................................... 33 
4 
EXPERIMENTAL PLAN ............................................................. 34 
4.1 
Trial Design ................................................................................................. 34 
4.2 
Number of Sites ........................................................................................... 35 
4.3 
Number of Participants ................................................................................ 35 
5 
INVESTIGATIONAL MEDICINAL PRODUCT ..................... 36 
5.1 
GWP42003-P Oral Solution ........................................................................ 36 
5.2 
Placebo Oral Solution .................................................................................. 36 
5.3 
Packaging, Storage, and Drug Accountability ............................................ 36 
5.3.1 
Packaging and Labelling ........................................................................... 36 
5.3.2 
Storage ...................................................................................................... 37 
5.3.3 
Supply and Return of Investigational Medicinal Product ......................... 38 
5.3.4 
Investigational Medicinal Product Accountability ................................... 38 
5.3.5 
Investigational Medicinal Product Adherence and Reminder 
System ....................................................................................................... 39 
6 
PARTICIPANT ELIGIBILITY ................................................... 42 


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6.1 
Inclusion Criteria ......................................................................................... 42 
6.2 
Exclusion Criteria ........................................................................................ 43 
7
PARTICIPANT ENROLMENT .................................................. 47
7.1 
Treatment Assignment ................................................................................ 47 
7.2 
Randomization............................................................................................. 47 
8
TREATMENT PROCEDURES ................................................... 48
8.1 
Investigational Medicinal Product Dosage, Administration, and 
Schedule ...................................................................................................... 48 
8.1.1 
Dose Administration ................................................................................. 48 
8.2 
Concomitant Therapy .................................................................................. 48 
8.3 
Prohibited Therapy During Trial Period ..................................................... 48 
8.4 
Compliance in Investigational Medicinal Product Administration ............. 49 
8.5 
Access to Blinded Treatment Assignment .................................................. 50 
9
TRIAL PROCEDURES ................................................................ 51
9.1 
Trial Procedures .......................................................................................... 51 
9.1.1 
Informed Consent ..................................................................................... 51 
9.1.2 
Rescreening ............................................................................................... 52 
9.1.3 
Contraception Requirements .................................................................... 52 
9.1.4 
Demographics ........................................................................................... 53 
9.1.5 
Medical History ........................................................................................ 53 
9.1.6 
Psychiatric History .................................................................................... 54 
9.1.7 
Concomitant Medication .......................................................................... 54 
9.1.8 
Physical Examination ............................................................................... 54 
9.1.9 
Vital Signs ................................................................................................ 54 
9.1.10 
12-lead Electrocardiogram ........................................................................ 55 
9.1.11 
Clinical Laboratory Sampling ................................................................... 55 
9.1.11.1 
Pharmacokinetic Blood Sampling ......................................................... 57 
9.1.11.2 
Biomarker Sampling ............................................................................. 57 
9.1.11.3 
Pharmacogenetic Blood Sampling ........................................................ 58 
9.1.12 
Randomization and Trial Management System ........................................ 58 
9.1.13 
Investigational Medicinal Product Adherence and Reminder 
System ....................................................................................................... 58 
9.1.14 
Questionnaires and Assessments Completed at Scheduled Visits ............ 59 


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9.1.14.1 
Extrapyramidal Symptom Rating Scale ................................................ 60 
9.1.14.2 
Columbia-Suicide Severity Rating Scale .............................................. 60 
9.1.14.3 
Mini-International Neuropsychiatric Interview for Psychotic 
Disorders Studies .................................................................................. 60 
9.1.14.4 
Positive and Negative Symptom Scale ................................................. 61 
9.1.14.4.1 
Structured Clinical Interview Positive and Negative 
Symptom Scale .................................................................................. 61 
9.1.14.4.2 
Informant Questionnaire Positive and Negative Symptom 
Scale .................................................................................................. 61 
9.1.14.5 
Clinical Global Impressions Questionnaire .......................................... 61 
9.1.14.6 
Calgary Depression Scale for Schizophrenia ........................................ 62 
9.1.14.7 
Brief Assessment of Cognition for Schizophrenia ................................ 62 
9.1.14.8 
Schizophrenia Quality of Life Scale ..................................................... 62 
9.1.14.9 
Basic Personal Traits Module of Multidimensional 
Psychological Questionnaire ................................................................. 63 
9.1.14.10 
Expectation Module of Multidimensional Psychological 
Questionnaire ........................................................................................ 63 
9.1.14.11 
Perception Module of Multidimensional Psychological 
Questionnaire ........................................................................................ 63 
9.1.14.12 
Patient Global Impression of Change ................................................... 63 
9.1.14.13 
Cannabis Use Survey ............................................................................ 63 
9.1.15 
Investigational Medicinal Product Accountability ................................... 64 
9.1.16 
Adverse Events ......................................................................................... 64 
9.2 
Special Circumstances ................................................................................. 64 
10 
INVESTIGATIONAL MEDICINAL PRODUCT 
DISCONTINUATION AND WITHDRAWAL .......................... 66 
11 
URGENT SAFETY MEASURES ................................................ 68 
12 
ADVERSE EVENT REPORTING .............................................. 69 
12.1 
Definitions ................................................................................................... 69 
12.1.1 
Adverse Event ........................................................................................... 69 
12.1.2 
Investigator ............................................................................................... 69 
12.2 
Serious Adverse Events ............................................................................... 69 
12.3 
Reporting Procedures for Serious Adverse Events ..................................... 70 
12.4 
Pregnancy .................................................................................................... 71 
12.5 
Causality Assessment .................................................................................. 71 


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12.6 
Reporting Procedures for All Adverse Events ............................................ 72 
12.7 
Follow-up Procedures for Adverse Events .................................................. 74 
12.8 
Potential Cases of Drug-induced Liver Injury ............................................ 74 
12.9 
Notification of Safety Information to Investigators, Regulatory 
Authorities and Institutional Review Board or Independent Ethics 
Committee ................................................................................................... 75 
13 
STATISTICAL CONSIDERATIONS ......................................... 77 
13.1 
Sample Size, Power, and Significance Levels ............................................ 77 
13.2 
Interim Analysis .......................................................................................... 77 
13.3 
Analysis Sets ............................................................................................... 77 
13.3.1 
Protocol Deviations .................................................................................. 79 
13.4 
General Considerations ............................................................................... 79 
13.5 
Accountability and Background Characteristics ......................................... 79 
13.5.1 
Enrolment and Disposition ....................................................................... 79 
13.5.2 
Baseline and Demographic Characteristics .............................................. 80 
13.5.3 
Medical History ........................................................................................ 80 
13.5.4 
Concomitant Medication .......................................................................... 80 
13.6 
Endpoints and Statistical Methods .............................................................. 80 
13.6.1 
Efficacy Analysis ...................................................................................... 80 
13.6.1.1 
Sensitivity Analysis ............................................................................... 81 
13.6.1.2 
Supplementary Analyses for Efficacy Analysis .................................... 81 
13.6.2 
Exploratory Endpoints .............................................................................. 82 
13.6.3 
Pharmacokinetics ...................................................................................... 84 
13.6.4 
Safety ........................................................................................................ 84 
13.6.4.1 
Treatment Compliance and Extent of Treatment Exposure .................. 85 
13.6.4.2 
Adverse Events ..................................................................................... 85 
13.6.4.3 
Vital Signs, 12-lead Electrocardiogram, Physical Examination, 
and Other Safety Data ........................................................................... 86 
13.6.4.4 
Clinical Laboratory Data ....................................................................... 86 
13.6.4.5 
Suicidality ............................................................................................. 86 
13.6.5 
Multidimensional Psychological Questionnaires ..................................... 86 
13.6.6 
Handling of Missing Data ......................................................................... 86 
14 
DATA MONITORING COMMITTEE ...................................... 87 
15 
REGULATORY AND ETHICAL OBLIGATIONS .................. 88 


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15.1 
Declaration of Helsinki ............................................................................... 88 
15.2 
Informed Consent ........................................................................................ 88 
15.3 
Institutional Review Board/Independent Ethics Committee ....................... 88 
15.4 
Pre-trial Documentation Requirements ....................................................... 89 
15.5 
Participant Confidentiality .......................................................................... 90 
15.6 
Genetics ....................................................................................................... 90 
16 
ADMINISTRATIVE AND LEGAL OBLIGATIONS ............... 92 
16.1 
Protocol Amendments and End of Trial or Termination ............................. 92 
16.2 
Trial Documentation and Storage................................................................ 92 
16.3 
Trial Monitoring and Data Collection ......................................................... 93 
16.4 
Quality Assurance ....................................................................................... 94 
16.5 
Compensation .............................................................................................. 94 
16.6 
Publication Policy........................................................................................ 95 
16.7 
Intellectual Property Rights ......................................................................... 95 
16.8 
Confidential Information ............................................................................. 95 
17 
REFERENCES .............................................................................. 96 
 
 


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List of Appendices 
Appendix 1 
SCHEDULE OF ASSESSMENTS ................................. 99 
Appendix 2 
Trial Personnel .............................................................. 103 
Appendix 2.1 
Investigator Details ....................................................... 103 
Appendix 2.2 
Sponsor Contact Details ................................................ 103 
Appendix 2.3 
Contract Research Organizations .................................. 104 
 
 
 


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List of In-text Tables 
Table 5.1-1 
Formulation of GWP42003-P Oral Solution .................. 36 
Table 5.2-1 
Formulation of Placebo Oral Solution ............................ 36 
Table 7.1-1 
Participant Treatment Assignment .................................. 47 
Table 9.1.11-1 
Biochemistry, Biomarkers, Hematology, Urinalysis, and 
Drug Screen .................................................................... 56 
 


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List of In-text Figures 
Figure 1-1 
Trial Design and Treatment Schematic ................................... 15 
 


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List of Abbreviations 
 
ADR 
Adverse drug reaction 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
AUC0-t 
Area under the concentration-time curve calculated to the last 
observable concentration at time t 
BACS 
Brief Assessment of Cognition for Schizophrenia 
BAS-MPsQ 
Basic Personal Traits Module of Multidimensional Psychological 
Questionnaire 
b.i.d. 
Twice daily 
BMI 
Body mass index 
CB 
Cannabinoid 
CBD 
Cannabidiol 
CBD-OS 
Cannabidiol oral solution 
CDSS 
Calgary Depression Scale for Schizophrenia 
CGI-I 
Clinical Global Impression of Improvement 
CGI-S 
Clinical Global Impression of Severity 
CIs 
Confidence intervals 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
Maximum measured plasma concentration 
COVID-19 
Coronavirus disease 2019 
CRO 
Contract research organization 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CST 
Clinical surveillance and training 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders 
ECG 
12-lead electrocardiogram 
EOT 
End of treatment 
eCRF 
Electronic case report form 


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ePRO 
Electronic participant reported outcome 
ESRS 
Extrapyramidal Symptom Rating Scale 
ET 
Early termination 
EU 
European Union 
EXP-MPsQ 
Expectation Module of Multidimensional Psychological 
Questionnaire 
FAAH 
Fatty acid amide hydrolase 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
GABA 
Gamma-aminobutyric acid 
GCP 
Good clinical practice 
GGT 
Gamma-glutamyl transferase 
GPR55 
G protein-coupled receptor 55 
GW 
GW Research Ltd 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent ethics committee 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IQ-PANSS 
Informant Questionnaire Positive and Negative Symptom Scale 
IRB 
Institutional review board 
LPI 
Lysophosphatidylinositol 
LS 
Least squares 
MAR 
Missing at random 
MINI 
Mini-International Neuropsychiatric Interview 
MMRM 
Mixed-effects model repeated measures 
MNAR 
Missing not at random 
PANSS 
Positive and Negative Symptom Scale 


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PANSS-G 
Positive and Negative Symptom Scale-General 
PANSS-N 
Positive and Negative Symptom Scale-Negative 
PANSS-P 
Positive and Negative Symptom Scale-Positive 
PANSS-T 
Positive and Negative Symptom Scale total 
PER-MPsQ 
Perception Module of Multidimensional Psychological 
Questionnaire 
PGIC 
Patient Global Impression of Change 
PI 
Principal investigator 
PK 
Pharmacokinetics 
PLA2 
Phospholipase A2 
PP 
Per protocol 
PRN 
Packaging reference number 
PVD 
Pharmacovigilance Department 
QTcF 
QT interval with Fridericia correction 
RNA 
Ribonucleic acid 
RTSM 
Randomization and Trial Supply Management 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCI-PANSS 
Structured Clinical Interview Positive and Negative Symptoms 
Scale 
SOC 
System organ class 
SUSAR 
Suspected unexpected serious adverse reaction 
SQLS 
Schizophrenia Quality of Life Scale 
TBL 
Total bilirubin 
TD 
Tardive dyskinesia 
TEAE 
Treatment-emergent adverse event 
THC 
Δ9-tetrahydrocannabinol 
TRH 
Thyrotropin-releasing hormone 
ULN 
Upper limit of normal 
US 
United States 
WOCBP 
Women of childbearing potential 
 


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Definition of Terms 
 
Term 
Definition 
Day 1 
The day a participant first receives investigational medicinal 
product during the treatment period in this trial. 
End of trial 
Last participant last visit or last contact, whichever occurs 
last. 
Enrolled participant 
Any participant who has provided written informed consent 
to take part in the trial. 
International 
normalized ratio 
A calculation made to standardize prothrombin time. 
Investigational 
medicinal product 
Term used to describe both investigational active product 
and reference therapy (placebo). 
Investigator 
Trial principal investigator or a formally delegated trial 
physician. 
QT interval 
A measure of the time between the start of the Q wave and 
the end of the T wave in the heart’s electrical cycle. 
 


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2 
OBJECTIVES/ENDPOINTS 
Objective  
Endpoint  
Efficacy  
x To evaluate the efficacy of 
GWP42003-P versus placebo 
after 12 weeks of treatment  
x Mean change from baseline to Week 12 in the 
following: 
 
Positive and Negative Symptoms Scale 
(PANSS) total (PANSS-T) score 
 
PANSS positive subscale (PANSS-P) score 
 
PANSS negative subscale (PANSS-N) score 
 
PANSS general subscale (PANSS-G) score 
 
Clinical Global Impression of Severity 
(CGI-S) score 
x Score at Week 12 in the Clinical Global 
Impression of Improvement (CGI-I) 
Safety 
x To evaluate the safety and 
tolerability of GWP42003-P  
x Changes in body weight, body mass index 
(BMI), and waist circumference 
x Changes in vital sign measurements 
x Adverse events (AEs) and adverse drug 
reactions (ADRs) 
x Extrapyramidal symptoms as assessed by the 
Extrapyramidal Symptom Rating Scale (ESRS) 
x Clinical laboratory test results 
x 12-lead electrocardiogram (ECG) parameters 
x Calgary Depression Scale for Schizophrenia 
(CDSS) 
x Suicidality as assessed by the Columbia-Suicide 
Severity Rating Scale (C-SSRS)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PI


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Objective  
Endpoint  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
x
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P
I
P
I
PI
PI


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3 
BACKGROUND AND RATIONALE 
3.1 
Disease 
Schizophrenia, a complex neurodevelopmental syndrome, results from gradual 
alterations in brain connectivity which may begin in utero, and symptoms (distorted 
thinking that affects language, perception, and sense of self) present and can persist 
for years before psychosis emerges1,2. Symptoms are categorized into positive (e.g., 
hallucinations, delusions, and speech disturbance), negative (e.g., social withdrawal, 
apathy, and loss of emotional response), and cognitive domains. Worldwide over 
21 million people live with schizophrenia, half of whom do not receive care2 and 
individuals’ ability to work and integrate socially is profoundly affected3. There is a 
slightly greater incidence in males who also experience an earlier onset4,5. However, 
regardless of sex, individuals with schizophrenia have a 2 to 3 fold increased risk of 
death from a range of comorbid somatic conditions (mostly cardiovascular and 
metabolic diseases) and suicide, the former attributable to unhealthy lifestyle, 
predisposition, and antipsychotic medication4,6. Individuals typically smoke, can be 
overweight or obese, suffer from hypertension, dyslipidemias, metabolic syndrome, 
and diabetes7 health concerns that are exacerbated by atypical antipsychotic 
medications causing weight gain and metabolic abnormalities compared with the 
extrapyramidal and tardive side effects of typical antipsychotic medications6. 
Antipsychotic medications, effective in the treatment of psychosis in most cases, act 
via antagonism of central dopamine receptor D21,8 however, numerous longitudinal 
studies have consistently noted significant heterogeneity and a high frequency of 
unfavorable outcomes in schizophrenia9,10,11. Relapse rates reach 80% to 85% during 
the first 5 years of illness12,13 with three quarters of individuals discontinuing 
antipsychotic treatment in 18 months14. A chronic course characterized by residual 
symptoms and/or relapses occurs in 34% to 57% of individuals11. Treatment response 
is a key determinant of subsequent outcome, as it is an essential precondition for 
remission and recovery15. Sub-optimally controlled psychotic symptoms are 
associated with a significant reduction in quality of life and functioning16. There is 
therefore a substantial unmet need for new and effective therapies to treat 
schizophrenia. 
Those individuals who respond to dopamine receptor blocking agents experience 
improvement in positive symptoms, but have little clinically significant improvement 
of negative symptoms and cognitive impairment3,17. 


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Disruption of excitatory/inhibitory balance in the central nervous system is thought to 
underlie a number of neurological syndromes including schizophrenia; for example, 
excess dopaminergic neurotransmission in the mesolimbic and striatal brain region 
leads to positive symptoms whilst negative symptoms are conversely thought to arise 
from reduced dopaminergic transmission in prefrontal brain regions18. Furthermore, 
glutamatergic hypofunction in cortico-striatal projections is thought to affect the 
thalamo cortical loop to cause exaggerated sensory flooding leading to psychosis. 
Circuit-based frameworks in schizophrenia suggest that hypofunction of hippocampal, 
fast spiking, interneurons lead to excessive glutamate release from pyramidal neurons, 
which drives dopamine release from dopaminergic neurons19. 
The antipsychotic properties of CBD have been demonstrated in a variety of in vitro 
and in vivo models. The efficacy of CBD was investigated in pharmacological models 
of relevance to schizophrenia, including amphetamine induced hyper-locomotion20,21, 
and cognitive, and social deficits induced by sub-chronic phencyclidine22. In addition, 
CBD appears to attenuate the extrapyramidal side effects induced by aripiprazole23. 
Clinically it has been shown that individuals with acute schizophrenia showed a 
significant improvement in PANSS-T, PANSS-P, PANSS-N, and PANSS general 
scores when treated with CBD; the clinical improvements were comparable with 
those achieved with amisulpride24. CBD treatment was well tolerated and compared 
with amisulpride, participants experienced significantly fewer extrapyramidal 
symptoms, less weight gain, and a lower increase of the galactorrhoea and sexual 
dysfunction marker, prolactin24. A GW sponsored trial showed participants with 
stable schizophrenia who had failed to optimally respond to existing antipsychotics, 
experienced a greater reduction from baseline in PANSS-P and a greater CGI-I after 
6 weeks of adjunctive therapy with GWP42003-P compared with placebo25. 
Given that schizophrenia is a complex disorder involving dysregulation of multiple 
pathways and biological systems, coupled with the fact that CBD does not act through 
the conventional route of D2 receptor antagonism, CBD may represent an 
antipsychotic with a novel mechanism of action. 
3.2 
Investigational Medicinal Product Background 
The investigational medicinal product (IMP), GWP42003-P, is formulated from 
extracts prepared from Cannabis sativa L. plants that have a defined chemical profile 
and contain consistent levels of CBD as the principal phytocannabinoid. Extracts from 
these plants are processed to yield purified (> 98%) CBD that contain < 0.1% (weight 


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by weight) Δ9-tetrahydrocannabinol (THC) (for oral formulations). The purified CBD 
is subsequently dissolved in excipients with added sweetener and flavoring. 
CBD has a very low affinity and lacks appreciable functional activity at the 
cannabinoid (CB) receptors type 1 and 2 (CB1 and CB2), as well as the dopamine 
receptor D226,27. CBD does not significantly interact with enzymes responsible for the 
synthesis and degradation of endocannabinoids, at clinically relevant 
concentrations28,29,30,31. Furthermore, considerable data exist describing the 
polypharmacology of CBD and its modulation of non-endocannabinoid system 
targets. Indeed, CBD has the ability to interact with multiple 7-transmembrane 
receptor systems, ion channels, transporters, and enzymes, reviewed in27,32. 
Putative molecular candidates for CBD relevant to schizophrenia, based on 
pharmacological engagement by CBD at therapeutically relevant concentrations, 
include equilibrative nucleoside transporter 1 inhibition and subsequent indirect 
agonism of adenosine receptor A1 (anxiolytic)32, and antagonism at G protein-coupled 
receptor 55 (GPR55), and agonism of transient receptor potential vanilloid 
receptors33. 
GPR55 is expressed by glutamatergic principal neurons in the hippocampus at their 
presynaptic terminals and postsynaptic membranes34. Based upon the hippocampal 
location of GPR55 receptors within a circuit-based framework in which hippocampal, 
fast spiking, interneuronal hypofunction, and reduced numbers thereof in 
schizophrenia, lead to excessive glutamate release from pyramidal neurons and thus 
dopamine release from dopaminergic neurons19, emerging data in non-clinical 
epilepsy models and electrophysiological recordings from brain slices in vitro 
suggests that CBD-mediated antagonism of GPR55 in the hippocampus could restore 
gamma-aminobutyric acid (GABA) receptor-mediated inhibition via 2 different 
mechanisms34: 
1. CBD-mediated antagonism of presynaptic GPR55 receptors present on 
hippocampal principal cells prevents the endogenous ligand LPI activating 
GPR55 receptors and the downstream induction of calcium-induced calcium 
release which ultimately inhibits vesicular glutamate release, dampening 
excitatory transmission. 
2. CBD-mediated antagonism of GPR55 receptors present on the postsynaptic 
membranes of hippocampal principal cells proximal to interneuron 
presynapses prevents LPI-mediated GPR55 activation and so the downstream, 


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gephyrin-mediated reduction in postsynaptic GABA receptor expression, 
enhancing inhibitory transmission. 
Importantly, CBD does not produce THC-like psychoactive effects. Further to this, 
CBD demonstrates anticonvulsant, antipsychotic, anxiolytic, neuroprotective, 
antioxidant and anti-inflammatory activity in a range of non-clinical models and has 
received Food and Drug Administration (FDA) approval for the treatment of seizures 
associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis 
complex in individuals 1 year of age and older35. 
3.3 
Rationale 
The rationale for this Phase 2b trial is based on the initial positive efficacy findings 
from a previous GW sponsored trial, which investigated the use of GWP42003-P as 
adjunctive therapy in participants with schizophrenia with inadequate response to 
ongoing antipsychotic treatment (GWAP1241), by further evaluating the efficacy and 
safety of GWP42003-P after 12 weeks of treatment in clinically stable schizophrenia 
participants experiencing inadequate response to antipsychotic treatment. 
3.4 
Clinical Hypothesis 
Treatment with GWP42003-P is associated with improvements in schizophrenia as 
measured by the mean change of participants’ PANSS-T score from baseline to 
Week 12. 


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Study Code: GWAP19030 
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4 
EXPERIMENTAL PLAN 
4.1 
Trial Design 
This is a randomized, double-blind, placebo-controlled, parallel-group, outpatient 
trial. The trial will compare the efficacy and safety of 2 dose levels of GWP42003-P 
(150 mg twice daily [b.i.d.] and 500 mg b.i.d.) versus placebo in participants with 
schizophrenia who are experiencing an inadequate response to ongoing antipsychotic 
treatment. 
The duration of the trial will be approximately 20 weeks, which includes a screening 
period (up to 4 weeks), a single-blind placebo run-in period (2 weeks), a double-blind 
treatment period (12 weeks), and a safety follow-up period (2 weeks). 
After signing the informed consent form (ICF), participants will enter the screening 
period (Visit 1). The investigator will submit participants’ eligibility forms for clinical 
surveillance and training (CST) review. The CST will evaluate the eligibility of 
participants and provide the outcome of the evaluation to the site. Participants cannot 
be enrolled until site personnel have received the final CST notification. Additional 
details for CST will be described in the study manual. At Visit 2 screened participants 
who continue to meet eligibility criteria will be randomized 1:1 to receive 150 mg 
b.i.d. or 500 mg b.i.d. dose matched volumes of placebo in a single-blind manner for 
the placebo run-in period. At Visit 3 (Day 1), participants who continue to meet the 
required eligibility criteria will be randomized 2:1 to receive GWP42003-P or placebo 
of equivalent volume to their placebo run-in allocation (Table 7.1-1) in a double-blind 
manner for the treatment period. 
Randomization will be stratified by region (North America, Europe) and by sex (male, 
female). 
A safety follow-up visit will be conducted 2 weeks after the last dose of IMP. If a 
participant discontinues IMP prematurely (i.e., before the end of the treatment period) 
they are required to attend an end of treatment (EOT) visit (±3 days) and complete the 
safety follow-up visit 2 weeks after their last dose. Participants are encouraged to 
attend any outstanding visits per the trial schema. If a participant prematurely 
discontinues IMP and withdraws from the trial without continuing trial visits as per 
the trial schema, they are required to attend an early termination (ET) visit upon 
withdrawal and complete the safety follow-up visit 2 weeks after their last dose. 
A schematic (Figure 1-1), depicts the overall trial design. More detailed information 
on treatment and trial procedures is provided in Section 8 and Section 9, respectively. 


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4.2 
Number of Sites 
Approximately 55 sites are expected to participate in this trial. The number of sites 
may be reduced or increased depending on recruitment performance. 
4.3 
Number of Participants 
Approximately 366 participants will be randomized following the placebo run-in to 
receive 1 of 2 dose levels of GWP42003-P (150 mg b.i.d. or 500 mg b.i.d.) or dose 
matching volume of placebo on a 2:2:1:1 basis. 
The sample size calculation is explained fully in Section 13.1. 


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5 
INVESTIGATIONAL MEDICINAL PRODUCT 
Please refer to the separate pharmacy manual for more detailed information on the 
IMP. 
5.1 
GWP42003-P Oral Solution 
GWP42003-P oral solution contains 100 mg/mL CBD dissolved in the excipients 
sesame oil and anhydrous ethanol (10% v/v), with sweetener (sucralose), and 
strawberry flavoring (Table 5.1-1). 
Table 5.1-1 
Formulation of GWP42003-P Oral Solution 
Ingredients 
Quantity 
CBD 
100 mg/mL 
Anhydrous ethanol 
79 mg/mL 
Sucralose 
0.5 mg/mL 
Strawberry flavor 
0.2 mg/mL 
Refined sesame oil 
make up to 1 mL 
5.2 
Placebo Oral Solution 
Placebo oral solution contains the excipients sesame oil and anhydrous ethanol, with 
added β-carotene (to color match GWP42003-P), sweetener (sucralose), and 
strawberry flavoring (Table 5.2-1). 
Table 5.2-1 
Formulation of Placebo Oral Solution 
Ingredients 
Quantity 
Anhydrous ethanol 
79 mg/mL 
Sucralose 
0.5 mg/mL 
Strawberry flavor 
0.2 mg/mL 
β-Carotenea 
Up to 0.1 mg/mL 
Refined sesame oil 
make up to 1 mL 
a β-Carotene concentration can be varied up to a maximum of 0.01% w/v as required to provide a 
consistent yellow-colored solution. 
5.3 
Packaging, Storage, and Drug Accountability 
5.3.1 
Packaging and Labelling 
The IMP will be manufactured, packaged, labelled and/or distributed by GW or 
delegated contractors. The IMP will be presented in 100 mL amber glass bottles with 
child-resistant screw caps and packed in cartons. Sufficient IMP will be dispensed at 
each relevant visit considering the dose group of the participant. A unique 
identification number will be used to identify each box and the IMP it contains. The 
unique identification number together with the packaging reference number (PRN) 
will permit full traceability of manufacture, pack, and label activities conducted at or 
on behalf of GW and the IMP information held on the Randomization and Trial 


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Supply Management (RTSM) system. GW will ensure that all IMP provided is fully 
labelled and packaged. The unique identification label will include the following 
information, as a minimum: 
x Sponsor’s name and address. 
x Product identification (e.g., “GWP42003-P or Placebo”). 
x Dose and/or Potency (e.g., “100 mg/mL GWP42003-P”). 
x Trial code number. 
x Expiry date. 
x Storage conditions. 
x Instruction: “For clinical trial use only”. 
x Instruction: “Keep out of the sight and reach of children”. 
x Any other information required by local regulatory authorities. 
In addition, any local country requirements in accordance with local drug law or 
regulatory requirement will be included in the final label text. 
Directions of use of IMP, name, address, and the telephone number of the investigator 
(or main contact for information about the product or the clinical trial) will be 
provided to each participant. 
5.3.2 
Storage 
The IMP must be stored at room temperature (do not store above 30°C) and must not 
be refrigerated or frozen. It must also be kept away from heat and direct sunlight. 
The IMP must be stored in compliance with the local regulations for a controlled drug 
(if applicable to country). The sponsor/representative must approve storage location 
and facilities. Temperature records of the clinical site storage location must be 
maintained (recording a minimum of Monday to Friday, excluding public holidays) 
from date of receipt of first shipment until end of trial dispensing period at each site. 
These records must contain at least the minimum and maximum daily temperatures 
and must be made available to the appropriate GW personnel for review throughout 
the trial. Temperature during transit of IMP to the site must be checked on receipt and 
compliance/non-compliance to the minimum and maximum recorded. 


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Should storage conditions deviate from these specified requirements, the GW trial 
monitor must be contacted immediately to confirm if the IMP remains suitable for 
use. IMP must be placed under quarantine until written confirmation is received that 
the IMP is suitable for use. 
Participants will be provided with instructions regarding home storage requirements 
for the IMP. 
5.3.3 
Supply and Return of Investigational Medicinal Product 
At trial initiation and thereafter, IMP will be shipped to the identified responsible 
person, such as the pharmacist, at the investigator’s site, who will check the amount 
received against the shipment request and condition of the drug (i.e., integrity, 
physical appearance, temperature during transit). Details of the IMP received will be 
recorded in the IMP accountability record (see Section 5.3.4). The site will 
acknowledge the IMP receipt and will complete any receipt forms required. IMP will 
be dispensed and returned as detailed in Section 8.4. As directed, all supplies, 
including unused, partially used, or empty containers, will be returned to GW/depot or 
destroyed at a GW-approved site if agreed in writing by the trial monitor. 
5.3.4 
Investigational Medicinal Product Accountability 
The investigator has overall responsibility for the accountability of all used and 
unused IMP. A drug accountability record for the IMPs must be kept current and must 
contain: 
x Trial code. 
x PRN, treatment number, date of receipt and quantity of IMP received. 
x Participant’s trial identification and or treatment number. 
x Date and quantity of IMP dispensed. 
x The initials of the dispensing/dosing party. 
x Date and quantity of IMP returned to the investigator. 
x IMP expiry dates. 
Refer to Appendix 1 for when IMP will be dispensed. Participants will be asked to 
return all IMP (used and unused) at each relevant visit (Appendix 1). The site will 
check the returned IMP against the usage recorded using the IMP adherence 
monitoring Platform (Section 5.3.5). Any discrepancies will be discussed with the 


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participant at the time of the visit and documented accordingly within the participant’s 
source documents. 
The investigator must inform GW promptly of all missing or unaccountable IMP. 
A record of returned IMP must be completed and included in the shipment of used 
and unused IMP to the relevant drug distribution depot. At the end of the trial, a 
record/statement of reconciliation must be completed and provided to GW. 
These inventories must be made available for inspection by an authorized GW 
representative and local officials or regulatory agency inspectors. 
Please refer to the separate pharmacy manual for more detailed information on the 
IMP. 
5.3.5 
Investigational Medicinal Product Adherence and Reminder 
System 
This trial will employ an IMP adherence monitoring platform (“Platform”) for all 
participants in the trial. The Platform uses artificial intelligence on smartphones to 
confirm IMP ingestion and built-in reminders and a communication system allow 
real-time intervention in case of IMP interruptions. In addition, participants will 
self-report their daily compliance of their current oral antipsychotic medication(s) 
within the Platform. 
Use of this Platform will in no way supersede or replace the prescribed IMP protocol 
of the participants. Because the Platform does not change the IMP protocol for the 
participants, but rather encourages adherence to the predefined protocol, use of this 
Platform presents minimal risk to the participants. Use of the Platform will be 
required for all participants in the trial. 
The monitoring Platform requires that all participants take each dose of IMP whilst 
using a smartphone. The Platform will be provided to participants preloaded on a 
smartphone, or participants will download the Platform onto their own mobile device 
during the second visit to site. 
When at home, participants will receive an IMP reminder at a time within a 
predefined window. This notification reminds participants to take their IMP dose 
whilst using the Platform. Participants will follow a series of prescribed steps in front 
of the front-facing webcam to visually confirm their ingestion of the IMP. The 
application on the smartphone will make an automated determination of whether the 
participant has properly taken their IMP at the prescribed time. There is no need for a 
healthcare provider to review the administration, nor would a healthcare provider 
need to be available at the time the participant takes their IMP. The amount of 


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guidance that the Platform provides to the participant is automatically reduced as the 
participant becomes more proficient at using the application. 
After the Platform confirms correct IMP ingestion, video recordings will be encrypted 
and transmitted to a secure centralized location for further analysis, including testing 
for duplicate enrolment. The captured data and video are reviewable through a “roles 
and rules” restricted system ensuring privacy of the information in accordance with 
United States (US) and applicable European data privacy laws, including General 
Data Protection Regulation European Union (EU) 2016/679. 
Phone numbers of the participants may also be collected and stored in an encrypted 
manner. Storing the phone numbers will allow for direct communication with 
participants, including automated messaging from the Platform and contact by 
healthcare providers or other monitoring personnel. At no time is the phone number 
visible to healthcare providers or monitoring personnel. Individuals outside the 
clinical sites will not be provided with participant names, nor will they be given 
access to participant medical records. 
The Platform may provide significant benefits to trial participants as well as to the 
other stakeholders in the trial. Participants will benefit from rapid and tailored 
intervention in case of non-adherence (drug interruptions) without having to visit the 
clinic for unscheduled visits. Healthcare providers will have access to real-time and 
continuous adherence data without having to rely on self-reported data or frequent 
trial visits by participants. Participants who regularly fail to take IMP will be 
contacted by healthcare providers or other trial monitoring personnel for retraining. 
The Platform Provider will protect participants’ personal information to the full extent 
required by law. However, information from this trial, including de-identified video 
recording(s) of participant performance of various actions, may be submitted to the 
trial site, and potentially to regulatory authorities. Both information obtained by the 
application, and information in the participant ICF, may be examined by the trial site 
or the trial site’s representatives, and may also be reviewed by the FDA and other 
regulatory agencies, Institutional Review Board(s) and or Ethics Committee(s). All 
parties are bound to safeguard the rights, safety and well-being of all clinical trial 
participants, and to maintain all information in confidence, with special consideration 
given to trials that may include vulnerable participants. 
The results of this trial may be presented at meetings or in publications; however, 
participants will not be identified by name in these presentations and/or publications. 
Information from this trial may also be retained by the Platform Provider for the 
purpose of improving the Platform, to allow for future analysis of various facial and 


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other parameters, the reporting of high level statistical analysis of the Platform, to 
improve the internal workings of the system running on the smartphone device, or for 
regulatory filings by the Platform Provider to support future applications for the 
provider’s product. 


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6 
PARTICIPANT ELIGIBILITY 
Investigators are responsible for confirming participant eligibility and will be required 
to maintain a log that includes limited information about all screened participants 
(e.g., initials, age, sex; as allowed per local regulations) and outcome of screening. 
6.1 
Inclusion Criteria 
For inclusion in the trial the participant must fulfill ALL of the following criteria: 
6.1.1 Male or female 18 to 55 years of age at the time of signing the ICF. 
6.1.2 Willing and able to give informed consent for participation in the trial. 
6.1.3 BMI of 18 to 40 kg/m2 inclusive and a body weight ≥ 50 kg at screening. 
6.1.4 Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis 
of schizophrenia, confirmed by the Mini-International Neuropsychiatric 
Interview (MINI) for Psychotic Disorders Studies. 
6.1.5 Clinically stable outpatient, based on the investigator’s judgment and 
defined by no signs of exacerbation of schizophrenia (no hospital 
admissions or prison incarcerations), and no evidence of an increased level 
of psychiatric care (including cognitive behavior rehabilitation or 
individual psychotherapy) within 12 weeks prior to screening. 
6.1.6 PANSS-T score of ≥ 60 and < 110 at screening and baseline visits. 
6.1.7 Score of ≥ 4 for at least 2 of the following PANSS items: delusions (P1), 
conceptual disorganization (P2), hallucinatory behavior (P3), 
suspiciousness (P6), somatic concern (G1), or unusual thought content 
(G9) at screening visit. 
6.1.8 Score ≥ 4 (at least moderately ill) on the CGI-S at screening visit. 
6.1.9 Undergoing treatment with at least 1 antipsychotic medication with no 
change in dosing, supported by documentation (including pharmacy 
records), for at least 8 weeks prior to screening and no change in 
antipsychotic medication dosing planned throughout the trial. 
6.1.10 Taking a maximum of 2 antipsychotic medications. For participants taking 
oral antipsychotic medications only, the sum of primary and secondary 
antipsychotic medications is ≤ 30 mg/day of oral olanzapine equivalents. 
For participants taking long-acting injectable antipsychotic medications, 
the dose is within the range approved and any secondary oral antipsychotic 
medications is ≤ 5 mg/day of oral olanzapine equivalents. 


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6.1.11 Documented response (at least partially) to treatment with current 
antipsychotic medications (e.g., treatment of recent exacerbation of 
psychotic symptoms) as assessed by the investigator or treating physician. 
Documentation can include medical records, pharmacy records, or 
corroboration in writing by the clinician(s) currently responsible for the 
participant’s psychiatric treatment. 
6.1.12 On a stable dose if taking concomitant psychotropic medications and 
within allowed limits, including antidepressants, anxiolytics, 
anticholinergics and/or antiepileptics for at least 4 weeks prior to screening 
(dose reductions ≤ 25% of total dose are permitted) with no plans to 
change dosing during the trial (i.e., from screening onwards). Valproic 
acid or any prescribed valproate product (valproate semisodium or 
valproate sodium) is disallowed within 4 weeks (i.e., more than 
5 half-lives) prior to the baseline visit. 
6.1.13 Willing to allow the responsible authorities to be notified of participation 
in the trial, if mandated by local law. 
6.2 
Exclusion Criteria 
The participant may not enter the trial if ANY of the following apply: 
Diagnosis and Psychiatric History 
6.2.1 Recent (within the last 3 months prior to screening) diagnosis of panic 
disorder, depressive episode, or other comorbid psychiatric conditions 
based on the MINI for Psychotic Disorders Studies (or DSM-5) OR has 
PANSS item G6 score of ≥ 5 (depression) at screening. 
6.2.2 Any psychiatric disorder that may interfere with the conduct of this trial, 
including but not limited to attention deficit hyperactivity disorder, 
pervasive developmental disorder, intellectual disability, personality 
disorder that might interfere with compliance or increase suicidal risk, 
manic or hypomanic episode, or any other psychotic disorder, as defined in 
the DSM-5. 
6.2.3 Current diagnosis or a history of substance use disorder according to 
DSM-5 criteria within 6 months prior to screening or prior chronic 
substance abuse judged likely to recur during the trial period by the 
investigator. Nicotine use or occasional cannabis use (≤ 3 days per week 
recreational cannabis use) is acceptable. Corroboration of the participant’s 
frequency of cannabis use by an adult informant (e.g., family member, 


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social worker, caseworker, residential facility staff, or nurse) should be 
obtained if the participant has a positive urine test for THC at screening. 
6.2.4 A positive drug screen for opiates, methadone, cocaine, amphetamines 
(including ecstasy), or barbiturates; a repeat drug screen may be done to 
verify the result. 
6.2.5 Any history of suicidal behavior or any suicidal ideation of type 4 or 5 on 
the adult C-SSRS within 1 month prior to screening. 
6.2.6 A ± ≥ 20% change in PANSS-T score during the placebo run-in period 
(Visit 2 to Visit 3). 
Treatment History 
6.2.7 Treatment-resistant schizophrenia as judged by the treating physician and 
as defined by having previously demonstrated no response to > 2 trials of 
antipsychotic trial medications at therapeutic doses or required clozapine 
therapy due to non-response to antipsychotic therapy within the previous 
6 months. 
6.2.8 Non-compliance, as assessed by antipsychotic medication and the IMP 
adherence monitoring Platform: 
 ≤ 75% compliance of current oral antipsychotic medication during the 
single-blind, placebo run-in periods (Visit 2 to Visit 3). 
 ≤ 75% compliance of current long-acting injectable antipsychotic 
medication as assessed by number of administrations falling more than 
1 week outside of the scheduled due date of administration, in the 
6 months prior to screening (Visit 1) and baseline (Visit 3). 
 ≤ 75% compliance of IMP during the single-blind, placebo run-in 
period (Visit 2 to Visit 3) for current IMP. 
6.2.9 Based on the investigator assessment; 
 current antipsychotic medication blood levels are below the therapeutic 
range if therapeutic drug monitoring is available for the 
antipsychotic(s) prescribed for the participant; or 
 there is no documentation confirming the administration of long-acting 
injectable antipsychotic medication within the approved dose range 
and as prescribed by the treating physician. 
Past and Current Medical History 


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6.2.10 History of moderate or severe head trauma (for example, loss of 
consciousness for more than 15 minutes) or other neurological disorders 
(including epilepsy), neurodegenerative disorder (Alzheimer’s disease, 
Parkinson’s disease, multiple sclerosis, Huntington’s disease, etc.) or 
systemic medical diseases that are, in the opinion of the investigator, likely 
to interfere with the conduct of the trial or confound the trial assessments. 
6.2.11 Tardive dyskinesia (TD) that is moderate to severe (i.e., a score of > 21 on 
the dyskinesia subscale of the ESRS at screening) or requires treatment. 
6.2.12 Any other significant disease, disorder, pending court proceedings or 
social circumstances (e.g., homelessness) which, in the opinion of the 
investigator, may either put the participant, other participants, or site staff 
at risk because of participation in the trial, may influence the result of the 
trial, or may affect the participant’s ability to take part in the trial. 
Other 
6.2.13 Any known or suspected hypersensitivity to cannabinoids or any of the 
excipients of the IMP, such as sesame seed oil. 
6.2.14 One or more laboratory values outside the normal range, based on the 
blood or urine samples taken at the screening visit, that are considered by 
the investigator to be clinically significant; or the participant has impaired 
hepatic function at screening, defined as serum alanine aminotransferase 
(ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal 
(ULN) or total bilirubin (TBL) > 1.5 × ULN or international normalized 
ratio (INR) > 1.2 (TBL ULN parameter not applicable for participants 
diagnosed with Gilbert’s disease). Note: Out-of-range laboratory values 
should be confirmed on retest within the allowed screening window. 
6.2.15 Clinically relevant abnormalities in the ECG measured at screening or 
randomization (including QT interval with Fridericia correction [QTcF] 
> 450 msec for males and > 470 msec for females, average of 
3 measurements). 
6.2.16 Positive serology panel (including hepatitis B surface antigen [HBsAg] 
and/or confirmed current hepatitis C infection [positive hepatitis C virus 
{HCV} antibody confirmed with reflex HCV RNA test]) and/or positive 
human immunodeficiency virus (HIV) antibody/p24 antigen screens. 


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6.2.17 Male and fertile (i.e., after puberty unless permanently sterile by bilateral 
orchidectomy) and with a partner of childbearing potential unless agree to 
ensure that they use male contraception (e.g., condom) or remain sexually 
abstinent during the trial and for 3 months after the last dose. 
6.2.18 Female of childbearing potential (i.e., following menarche until becoming 
postmenopausal for ≥ 12 consecutive months unless permanently sterile by 
hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) unless 
agree to use highly effective contraception (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 [provided partner is the sole 
sexual partner and has received medical assessment of the surgical 
success], true sexual abstinence) during the trial (i.e., from screening) and 
for 3 months after the last dose. 
6.2.19 Female who is pregnant (positive pregnancy test), lactating, or planning 
pregnancy during the trial or within 12 weeks after the last dose. 
6.2.20 Received an IMP within 12 weeks prior to the screening visit. 
6.2.21 Donated blood within 12 weeks prior to the screening visit and is 
unwilling to abstain from donation of blood during the trial. 
6.2.22 Previously randomized into the placebo run-in period of this trial. 
6.2.23 Travel outside the country of residence planned during the trial, unless the 
participant has confirmation that the IMP is permitted in the destination 
country. 
6.2.24 Currently using or within 3 months of screening has used CBD oil or 
purified CBD preparations and is unwilling to abstain for the duration of 
the trial. 


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7 
PARTICIPANT ENROLMENT 
Before participants enter the trial, GW requires a copy of the relevant site’s 
institutional review board (IRB) or independent ethics committee (IEC) written 
approval of the protocol, ICF, and other participant information material. Participants 
will be considered enrolled in the trial from the time of providing written informed 
consent. All participants must personally sign and date the consent form prior to any 
procedures being performed (refer to Section 15.2). 
7.1 
Treatment Assignment 
At the start of Visit 1, enrolled participants will be allocated a unique participant 
number. After completion of assessments and confirmation of eligibility at Visit 2, 
participants will be assigned a unique treatment number and will be randomized 1:1 to 
receive 150 mg b.i.d. or 500 mg b.i.d. dose matched volumes of placebo in a 
single-blind manner for the placebo run-in period. At Visit 3 (Day 1) participants who 
continue to meet the required eligibility criteria will be randomized 2:1 to receive 
GWP42003-P or placebo of equivalent volume to their placebo run-in allocation 
(Table 7.1-1) in a double-blind manner for the treatment period. GW will provide all 
IMP in a packed and labelled state and the RTSM system will identify the pack 
number to be dispensed to the participant at each relevant visit, according to the 
treatment assigned in the randomization schedule. 
Table 7.1-1 
Participant Treatment Assignment 
Single-blind Allocation (Run-in Period) 
Double-blind Allocation (Treatment Period) 
150 mg b.i.d. placebo 
150 mg b.i.d. GWP42003-P 
150 mg b.i.d. placebo 
500 mg b.i.d. placebo 
500 mg b.i.d. GWP42003-P 
500 mg b.i.d. placebo 
b.i.d. = twice daily. 
7.2 
Randomization 
The allocation of IMP to treatment number will be done according to a randomization 
schedule produced by an independent statistician. The assignment during the placebo 
run-in period will be single-blinded and assignment during the treatment period will 
be double-blinded. The randomization schedule will be held centrally and not 
divulged to any other person involved in the trial until the database has been locked 
and unblinding authorized by the relevant GW personnel. For access to blinded 
treatment assignment, see Section 8.5. 


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8 
TREATMENT PROCEDURES 
8.1 
Investigational Medicinal Product Dosage, Administration, and 
Schedule 
The IMP will be presented as an oral solution containing 100 mg/mL GWP42003-P or 
only excipients (in the case of placebo). For details regarding IMP formulations, see 
Section 5. 
8.1.1 
Dose Administration 
IMP will be self-administered orally (swallowed) b.i.d. (e.g., morning and evening) 
preferably within 30 minutes of a meal using the syringe(s) provided. The IMP may 
be taken with other concomitant medications, as directed by the investigator. During 
the PK visits, the participants’ morning dose of IMP will be administered at the trial 
site following predose PK blood draws, with a standardized meal of at least 300 kcal 
under the supervision of site staff. Staff should observe dosing and provide feedback 
on correct dosing methods if necessary. 
8.2 
Concomitant Therapy 
Participants will be taking at least 1 antipsychotic medication, or a maximum of 
2 antipsychotic medications. For participants taking oral antipsychotic medications 
only, the sum of primary and secondary antipsychotic medication is ≤ 30 mg/day of 
oral olanzapine equivalents. For participants taking long-acting injectable 
antipsychotic medications, the dose is within the range approved and any and 
secondary oral antipsychotic medications is ≤ 5 mg/day of oral olanzapine 
equivalents. 
Concomitant psychotropic medications including antidepressants, anxiolytics, 
anticholinergics, and/or antiepileptics are allowed provided that the current dose has 
been unchanged for the 4 weeks prior to screening (dose reductions permitted) with 
no plans to change dosing during the trial (i.e., from screening onwards). 
Any medication, other than the IMP, taken during the trial must be recorded in the 
electronic case report form (eCRF). 
8.3 
Prohibited Therapy During Trial Period 
The following medications are prohibited for the duration of the trial beginning from 
the date of the screening visit. If applicable, the possible effects of these medications 
on the efficacy endpoints will be considered during the assessment of the evaluable 
period. 
x Cannabis or THC-based products within 24 hours prior to Visits 1, 3, and 7. 


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x Valproic acid or any prescribed valproate product (valproate semisodium or 
valproate sodium) and psychostimulants taken within 4 weeks (i.e., more than 
5 half-lives) prior to the baseline visit. 
x Clozapine taken within 6 months prior to screening. 
The following medications are restricted for the duration of the trial beginning from 
the date of the screening visit until the completion of assessments at Visit 7 or the 
discontinuation visit: 
x Daily doses of anticholinergic drugs for the treatment of extrapyramidal side 
effects will be limited to 1 mg/day or less of benztropine or biperiden or 
2 mg/day or less of trihexyphenidyl or equivalents. 
x Daily doses of benzodiazepine receptor agonists will be limited to 2 mg/day or 
less of lorazepam or equivalents. Benzodiazepines will be prohibited within 
24 hours prior to Visits 1, 3, and 7. 
x Daily doses of hypnotics will be limited to 10 mg/day of zolpidem or 
zopiclone or 3 mg/day of eszopiclone. Hypnotics will be prohibited within 
24 hours prior to Visits 1, 3, and 7. 
x Daily doses of tricyclic antidepressants will be limited to 100 mg/day or less 
of amitriptyline or equivalents. 
x Lithium, tricyclics, and other psychotropic medications that may affect 
cognition should be discussed with sponsor prior to enrolling the participant. 
8.4 
Compliance in Investigational Medicinal Product Administration 
Refer to Appendix 1 for when IMP will be dispensed. Further guidance on IMP 
dispensing will be provided in a separate pharmacy manual. 
Please see Section 5.3.5 for details on the IMP adherence and reminder system. 
Participants should return all IMP (used and unused) at each relevant visit 
(Appendix 1), and participants must return placebo IMP from the placebo run-in 
period before randomization to the treatment period. The IMP will be checked, and 
any discrepancies discussed with the participant at the time of the visit and 
documented accordingly within the participant’s source documents. 
The investigator must inform GW promptly of all missing or unaccountable IMP. 
Records of IMP accountability will be maintained according to Section 5.3.4. 


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In cases where participants are not able to attend trial visits due to special 
circumstances (e.g., Coronavirus disease 2019 [COVID-19] pandemic), the 
investigator will discuss with the sponsor potential mitigation approaches for IMP 
dispensing, secure delivery, and collection. 
8.5 
Access to Blinded Treatment Assignment 
The identity of IMP assigned to participants will be held by the RTSM system. The 
principal investigator (PI) at each site, or his/her designee, is responsible for ensuring 
that information on how to access the RTSM system for an individual participant is 
available to the relevant staff in case of an emergency and unblinding is required. A 
participant’s treatment assignment should only be unblinded when knowledge of the 
treatment is essential to decide on the medical management of the participant. 
Unblinding for any other reason will be considered a protocol deviation. 
The investigator is encouraged to contact GW to discuss the rationale for unblinding 
prior to doing so. However, to prevent delays to the investigator or medical personnel 
responding to a potentially emergent situation, unblinding of IMP will not be 
dependent upon the investigator receiving approval from GW (i.e., the investigator 
will be able to obtain the code break information independent of contacting GW). 
If the investigator does unblind, they must contact GW within 1 working day of the 
event and must document the time, date, and reason(s) for unblinding in the 
participant’s medical notes and on the eCRF. 


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9 
TRIAL PROCEDURES 
A list of the required trial procedures is provided in the schedule of assessments 
(Appendix 1). Assessments or tests that are not completed and examinations that were 
not conducted must be reported on the electronic eCRF. 
Participants will be issued with the participant information and ICF. Following 
adequate time to discuss the trial with the investigator, nurse or relatives, participants 
who provide written informed consent will be screened for entry into the trial. 
The location of the source data for the trial procedures (Appendix 1) will be 
documented, per site, in a signed source data verification plan; for further details see 
Section 16.2. 
9.1 
Trial Procedures 
9.1.1 
Informed Consent 
All participants with an adequate level of understanding must personally sign and date 
the IRB/IEC-approved ICF before any trial-specific procedures are performed or any 
participant-related data are recorded for the trial. For participants with an insufficient 
level of understanding of what is proposed, only parent(s)/legal representative consent 
will be sought. If an adult participant is unable to read (illiterate or visually impaired), 
or is physically unable to speak or write, an impartial witness should be present 
during the entire informed consent discussion. After the ICF is read and explained to 
the participant and after the participant has orally consented to participation in the 
trial and has signed and dated the ICF (if capable of doing so), the witness should also 
sign and personally date the ICF. By signing the ICF, the witness attests that the 
information in the ICF was accurately explained to and apparently understood by the 
participant and that informed consent was freely given by the participant. 
If the participant cannot write, they can give consent by “making their mark” on the 
consent form (e.g., writing an “X”). 
Informed consent should be taken in accordance with the guidance provided in 
ICH E6 by an appropriately trained and delegated site staff member. A physician 
should be available to answer any questions from the participant. The original signed 
ICF should be retained and a copy provided to the participant. Participants will be 
given the option of being informed about the summary outcome and results of the trial 
as part of the ICF. For further details, see Section 15.2. 


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9.1.2 
Rescreening 
If an individual has not met all eligibility criteria at the end of the screening period, 
they will be registered as a screen fail. Screen fail participants may be eligible for 
rescreening once. However, participants may not be rescreened if they did not meet 
PANSS-T or CGI-S eligibility criteria on the first screening. 
Rescreened participants must first be registered as screen failures and subsequently 
registered as rescreens. Once the participant is registered as rescreened, a new 
screening window will begin. For all rescreens, all screening procedures, including 
ICF, must be repeated. Sites should discuss planned rescreens with the medical 
monitor prior to rescreening. 
9.1.3 
Contraception Requirements 
Contraception requirements must be assessed by the investigator on a case by case 
basis. Where applicable, the participant or their partner must use highly effective 
contraception for the duration of the trial and for 3 months thereafter. 
To be eligible for the trial, male participants who are fertile (i.e., after puberty unless 
permanently sterile by bilateral orchidectomy) must agree that they are willing to use 
male contraception (condom) or remain sexually abstinent during the trial and for 
3 months thereafter. 
To be eligible for the trial, female participants of childbearing potential (i.e., fertile, 
following menarche and until becoming postmenopausal for ≥ 12 consecutive months 
unless permanently sterile by hysterectomy, bilateral salpingectomy, or bilateral 
oophorectomy, as per the definition of woman of childbearing potential) must agree to 
use highly effective birth control methods for the duration of the trial and for 
3 months thereafter. Highly effective methods of birth control are defined as those, 
alone or in combination, that result in a low failure rate (i.e., less than 1% per year) 
when used consistently and correctly. Such methods include36: 
x Combined (estrogen and progestogen containing) hormonal contraception 
associated with the inhibition of ovulation: 
 Oral. 
 Intravaginal. 
 Transdermal. 


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x Progestogen-only hormonal contraception associated with inhibition of 
ovulation: 
 Oral. 
 Injectable. 
 Implantable. 
x Intrauterine devices. 
x Intrauterine hormone-releasing systems. 
x Bilateral tubal occlusion. 
x Vasectomized partner, provided that partner is the sole sexual partner of the 
participant of childbearing potential and that the vasectomized partner has 
received medical assessment of the surgical success. 
x Sexual abstinence, only if defined as refraining from heterosexual intercourse 
during the entire period of risk associated with the trial treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration 
of the clinical trial and the preferred and usual lifestyle of the participant. 
Abstinence, as referenced above, is only acceptable as true abstinence: when 
this is in line with the preferred and usual lifestyle of the participant; periodic 
abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) 
and withdrawal (coitus interruptus), spermicides only, and lactational 
amenorrhea method are not acceptable methods of contraception36. 
9.1.4 
Demographics 
The following information will be obtained for each participant: date of birth, sex, 
race (as allowed per local regulations), and ethnic origin. 
9.1.5 
Medical History 
Relevant, significant medical history will be obtained at screening (Visit 1) and is 
defined as any condition or disease that meets any of the following criteria: 
x May affect the condition under study in this trial. 
x Is ongoing on entry into the trial. 
x Suspected or confirmed COVID-19 infection (or other significant infectious 
diseases) within 1 year prior to screening. 


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9.1.6 
Psychiatric History 
The following information will be obtained for each participant: 
x Date of first diagnosis of schizophrenia. 
x Details of comorbid psychiatric disorders, including dates of onset and 
remission. 
x Date of most recent relapse or acute exacerbation of schizophrenia. 
x History of prior antipsychotic medication treatments for schizophrenia, 
including dose, start and end dates as well as clinically significant response to 
treatment (yes/no). 
9.1.7 
Concomitant Medication 
Details of all current and recent non-psychotropic medication (i.e., taken within the 
previous 2 weeks), will be recorded. Details of all current and recent psychotropic 
medication, including antipsychotic medication, antidepressants, anticholinergics, 
antiepileptics, and/or lithium taken within the previous 4 weeks will be recorded and 
reviewed at each subsequent visit. All antipsychotic medications should have been 
maintained at a stable dose over a period of 4 weeks prior to screening and 
participants must agree to maintain these at a stable dose throughout the duration of 
the trial; however concomitant medications may be changed if required in response to 
a safety concern. Any changes in concomitant medication during the trial must be 
recorded on the eCRF at trial visits. The time of antipsychotic medications will be 
collected at PK sampling visits. 
Any vaccination related to COVID-19 that was received within the last 12 months 
prior to screening should be recorded as a concomitant medication. The information 
recorded should include the vaccine manufacturer and the dates of administration, 
with differing start and end dates if more than 1 dose is received. 
The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
9.1.8 
Physical Examination 
A full physical examination or symptom-directed physical examination will be 
performed at the timepoints specified in the schedule of assessments (Appendix 1). 
9.1.9 
Vital Signs 
Vital signs will include systolic/diastolic blood pressure, heart rate, respiratory rate, 
and temperature. Blood pressure should be taken after the participant has been in a 


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supine position in a rested and calm state for at least 5 minutes. Blood pressure must 
be recorded using the same arm throughout the trial, where possible. 
Vital signs should be collected prior to clinical laboratory assessments and PK 
sampling if possible. 
Body weight, BMI, waist circumference, and height (collected at Visit 1 only) will 
also be collected. The method for measuring waist circumference will be detailed in a 
separate manual. 
9.1.10 
12-lead Electrocardiogram 
An ECG will be performed after 5 minutes in a supine position, if possible. A 
physician must review the ECG and any abnormal findings considered to indicate 
significant medical history or AEs must be recorded appropriately in the eCRF. 
Additional ECG measurements can be taken at any time during the trial, if clinically 
indicated. ECG collection requirements and processing procedures will be detailed in 
a separate manual. 
ECG should be collected prior to clinical laboratory assessments and PK sampling if 
possible. 
9.1.11 
Clinical Laboratory Sampling 
The investigator should use their judgment and knowledge of the participant to 
determine when best to collect the blood and urine samples in order to mitigate the 
risk that invasive procedures may cause the participant to become stressed, thereby 
affecting the results of other assessments. 
Laboratory tests will include hematology, biochemistry, urinalysis, a drug screen, and 
a urine/serum pregnancy test (for women of childbearing potential [WOCBP]). 
Analysis of all clinical blood samples and serum pregnancy tests (for WOCBP), will 
be conducted at a central clinical laboratory. Blood sample volume requirements and 
processing procedures will be detailed in a separate laboratory manual. 
Urine samples for biochemistry will be analyzed at the trial site by use of a dipstick 
with any relevant findings being sent for further urinalysis at the central laboratory 
(urinalysis, microscopy, culture and sensitivity, as applicable). In cases where urine 
samples cannot be analyzed at the site due to local regulations, a full set of urine 
samples should be sent to the central laboratory for analysis. Urine sample volume 
requirements and processing procedures will be detailed in a separate laboratory 
manual. 


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The investigator and trial monitor will be provided with a list of the normal ranges 
used by the testing laboratory for all variables assayed during the trial and a statement 
of accreditation (or similar) for the laboratory. Clinical laboratory sample parameters 
are detailed in Table 9.1.11-1. 
Table 9.1.11-1 
Biochemistry, Biomarkers, Hematology, Urinalysis, and 
Drug Screen 
Biochemistry 
(Serum)a  
Biomarkers 
Hematology 
(Whole 
Blood)a  
Urinalysis 
(Urine)b 
Pregnancy 
Test  
Drug Screen 
(Urinea) 
Alanine 
aminotransferase 
LPI 
Hematocrit 
Blood 
Seruma 
Alcohol 
Albumin 
Phospholipase 
A2  
Hemoglobin Glucose 
Urineb 
Amphetamines 
(including 
ecstasy) 
Alkaline 
phosphatase 
Complement C4 
Mean cell 
volume 
Nitrites 
 
Barbiturates 
Aspartate 
aminotransferase 
Interleukin-6 
Mean 
corpuscular 
hemoglobin 
pH 
 
Benzodiazepines 
Calcium 
Genomic DNAd 
Platelets 
Protein 
 
Cocaine 
Creatinine 
Genomic RNAd 
Red blood 
cell count 
White blood 
cells 
 
Methadone 
Creatinine 
clearance 
 
White blood 
cell count 
with 
automated 
differential 
 
 
Opiates 
GGT 
 
 
 
 
THC  
HBsAg 
 
 
 
 
 
HCV antibodyc 
 
 
 
 
 
HIV antibody 
 
 
 
 
 
INR 
 
 
 
 
 
Potassium 
 
 
 
 
 
Prothrombin time 
(plasma) 
 
 
 
 
 
Sodium 
 
 
 
 
 
Total bilirubin 
 
 
 
 
 
Total protein 
 
 
 
 
 
Urea (blood urea 
nitrogen) 
 
 
 
 
 
GGT = gamma-glutamyl-transferase; HBsAG = hepatitis B surface antigen; HCV = hepatitis C 
virus; HIV = human immunodeficiency virus; INR = international normalized ratio; 
LPI =  lysophosphatidylinositol. 
a Analyzed at a central laboratory. 
b Analyzed at the trial site by use of a dipstick (if allowed per local regulations). 
c Positive HCV antibody to be confirmed with reflex HCV RNA test. 
d Genetic analysis component of the study is optional. 


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Investigators at trial sites will be notified of safety laboratory test results. All 
laboratory results will be reviewed, and the reports signed and dated by an 
investigator. Any results considered to be of clinical significance must be addressed 
and followed up as clinically appropriate. The results of drug screening will be 
reported back to the trial site for confirmation of eligibility. All laboratory results 
considered to represent an AE must be documented on the eCRF. For reporting and 
follow-up of potential cases of drug-induced liver injury, see Section 12.8. Repeat 
samples will be taken, if required, for clinical follow-up or if the sample is lost or 
damaged. Any abnormal EOT clinical laboratory result of clinical significance must 
be repeated at regular intervals until it returns to normal, or until an investigator is 
satisfied that the abnormality is not related to the IMP and needs no further 
investigation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PI
PI
PI
PI
PI
PI


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9.1.12 
Randomization and Trial Management System 
The RTSM system will be used to assign participants to treatment arms, manage IMP 
supply, and to provide treatment allocation information in the event of participant 
unblinding. The RTSM system information can be accessed via the eCRF. A member 
of the trial team must register in the eCRF at each clinic visit in order to: 
x Obtain a participant number. 
x Randomize a participant. 
x Obtain dispensing information. 
x Provide completion/ET information. 
Training will be given to all sites prior to the start of the trial. 
9.1.13 
Investigational Medicinal Product Adherence and Reminder 
System 
The site staff will assist the participant with downloading the IMP adherence and 
reminder system application on their personal smartphone, or 1 will be provided to the 
participant. 
The site staff will guide the participant through the automated registration and training 
steps in the application. 
PI


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Throughout the trial, the site staff will regularly check IMP adherence and reminder 
system dashboard and monitor the communications from AiCure, the company 
providing the service, to identify participants who are not adherent with taking IMP. 
The site staff will follow-up with participants to reinforce the importance of taking the 
IMP as directed and work with trial participants to improve their adherence as and 
when necessary. 
Prior to receiving IMP during Visits 2 and 3 participants will watch a training video. 
The aim of the training is to shape proper understanding of the clinical trial 
characteristics, its goals and means, in order to clarify expectations and reduce risk of 
placebo response in participants. 
9.1.14 
Questionnaires and Assessments Completed at Scheduled 
Visits 
Investigators or his/her qualified designee must have completed the sponsor specified 
training for each questionnaire (where appropriate), before any questionnaires are 
completed, and some additional training certification may be required prior to site 
activation. To ensure consistency, the same staff member (where possible) should 
complete the questionnaires for each participant throughout the trial. 
The investigator/trained delegates will complete the ESRS, adult C-SSRS, MINI for 
Psychotic Disorders Studies, PANSS, CGI-I, CGI-S, and CDSS. Every effort should 
be made to include informant information in the PANSS assessment through 
administration of the Informant Questionnaire (IQ)-PANSS. Informants may be 
contacted by phone if not able to attend every trial visit. If contact with a participant’s 
informant cannot be made within 3-day window from the date of the study visit, either 
by phone or in person, then the informant interview should not be considered a barrier 
to visit progression. Participants’ responses to the structured clinical interview 
(SCI)-PANSS will be audiotaped and both the PANSS assessment and recorded 
interview and audiotapes will be reviewed by a third party at certain visits to assess 
accuracy of scoring and provide feedback to investigators throughout the trial. Scores 
will need to be uploaded to the third-party vendor’s Platform for this review to occur 
in a timely manner. Investigators/trained delegates who are unable to score 
participants in a reliable manner may have their ability to rate participants in the trial 
revoked by the sponsor. 
Participants will complete the BACS, SQLS, PGIC, Basic Personal Traits Module of 
Multidimensional Psychological Questionnaire (BAS-MPsQ), Expectation Module of 
Multidimensional Psychological Questionnaire (EXP-MPsQ), Perception Module of 


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Multidimensional Psychological Questionnaire (PER-MPsQ), and the cannabis use 
survey. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.1.14.2 
Columbia-Suicide Severity Rating Scale 
The definitions of behavioral suicidal events used in this scale are based on those used 
in the Columbia-Suicide History Form. Questions are asked on suicidal behavior, 
suicidal ideation, and intensity of ideation. At screening (Visit 1), questions will be in 
relation to lifetime experiences. Questioning at all subsequent visits (see Appendix 1) 
will be in relation to the last assessment (since last visit). The adult C-SSRS will be 
used for all participants. 
9.1.14.3 
Mini-International Neuropsychiatric Interview for Psychotic 
Disorders Studies 
The MINI for Psychotic Disorders Studies38 is a short structured diagnostic interview, 
developed jointly by psychiatrists and clinicians in the US and Europe, for among 
others DSM-5 psychiatric disorders. With an administration time of approximately 
15 minutes, it meets the need for a short but accurate structured psychiatric interview 
for multisite clinical trials. In order to keep it short it focuses on the existence of 
current disorders. For each disorder, 1 or 2 screening questions rule out the diagnosis 
PI


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when answered negatively. Probes for severity, disability or medically explained 
symptoms are not explored symptom-by-symptom. 
9.1.14.4 
Positive and Negative Symptom Scale 
The PANSS assessment is a medical scale used for measuring symptom severity of 
participants with schizophrenia or related psychotic disorder. The name denotes to the 
2 types of symptoms in schizophrenia, as defined by the American Psychiatric 
Association: positive symptoms, which refer to an excess or distortion of normal 
functions (e.g., hallucinations and delusions), and negative symptoms, which 
represent a diminution or loss of normal functions. It is a 30-item rating instrument 
that assesses the positive and negative symptoms of schizophrenia as well as 
symptoms of general psychopathology. A PANSS-T score is derived from the sum of 
the 30 items and the PANSS items are also grouped into 3 subscales: positive, 
negative, and general. Individual items are rated on a 7-point scale, where 1 = absent 
and 7 = extreme. 
9.1.14.4.1 
Structured Clinical Interview Positive and Negative 
Symptom Scale 
To optimize the instrument's objectivity, the SCI-PANSS was developed to secure 
reliable information. The SCI-PANSS interview is used to gather information 
objectively prior to completing the PANSS assessment. 
9.1.14.4.2 
Informant Questionnaire Positive and Negative Symptom 
Scale 
The IQ-PANSS questionnaire evaluates phenomenological presentation in a reliable 
and valid manner. Through item definitions, statements, and questions, the 
questionnaire ensures that all information related to behavioral presence, frequency, 
and the participant's responsiveness is obtained during interviews with family 
members, healthcare providers, or other informants. 
9.1.14.5 
Clinical Global Impressions Questionnaire 
The CGI is split into 2 scales. The CGI-S and the CGI-I. 
The CGI-S is a 7-point scale used to rate the severity of participants’ illness at the 
time of assessment. Considering total clinical experience, a participant will be 
assessed on severity of mental illness at the time of rating 1 = normal, not at all ill; 
2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 
6 = severely ill; or 7 = extremely ill. 


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The CGI-I, is a 7-point scale that requires the clinician to assess how much the 
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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.1.14.7 
Brief Assessment of Cognition for Schizophrenia 
The BACS is an instrument used to assess the aspects of cognition found to be the 
most impaired and the most strongly correlated with outcome in participants with 
schizophrenia or related psychotic disorder. The BACS will take about 35 minutes to 
complete and comprises 6 domains: verbal memory; working memory; motor speed; 
verbal fluency; attention and speed information processing, and executive functions. 
A score is obtained for each domain and a composite summary score is also calculated 
as the average of the scores from the 6 domains. An increase in score is indicative of 
an improvement in cognition. 
9.1.14.8 
Schizophrenia Quality of Life Scale 
The SQLS was developed to measure health-related quality of life in people with 
schizophrenia41. It comprises 30 items incorporated in 3 domains: psychosocial 
(15 items), motivation and energy (7 items), and symptoms and side effects (8 items). 
All except 4 items are scored on a 5-point Likert-type scale (0 = never, 1 = rarely, 
2 = sometimes, 3 = often, 4 = always), with the exceptional 4 items being reverse 
coded (0 = always, 1 = often, 2 = sometimes, 3 = rarely, 4 = never). Individual 
domain and total scores are standardized by a scoring algorithm with higher scores 
indicating comparatively lower quality of life. The SQLS is estimated to take 
approximately 5 to 10 minutes to complete. 
PI


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9.1.14.12 
Patient Global Impression of Change 
The PGIC comprises a question to be rated on a 7-point scale. The markers are: very 
much improved, much improved, slightly improved, no change, slightly worse, much 
worse, and very much worse. 
9.1.14.13 
Cannabis Use Survey 
The cannabis use survey will provide the following information, at screening only: 
x Age of first use. 
x Duration since first regular use (years). 
x Currently using/used cannabis within the last month (yes, no). 
x Regularly using cannabis once per week or more (yes, no). 
x Most common route of current administration (smoked, vaped, oral). 
PI


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All time points thereafter: 
x The number of days used in last 7 days will be collected weekly via electronic 
participant reported outcome (ePRO) using the IMP adherence monitoring 
Platform. 
x Average grams per occasion will be collected weekly via ePRO using the IMP 
adherence monitoring Platform. 
9.1.15 
Investigational Medicinal Product Accountability 
Records of IMP accountability will be maintained according to Section 5.3.4. 
Refer to Appendix 1 for further details on when IMP will be dispensed. 
Participants will be asked to return all IMP (e.g., used and unused) at relevant visits 
(Appendix 1). The site will check the returned IMP against the expected usage. Any 
discrepancies will be discussed with the participant and documented accordingly 
within the participant’s source documents. 
9.1.16 
Adverse Events 
All AEs will be recorded on the eCRF. All AEs occurring during the trial, whether 
attributed to the IMP or not, observed by the investigator or reported by the 
participant will be recorded in the eCRF, questioning the participant further if 
necessary. 
Serious adverse events (SAEs) must be reported to GW Pharmacovigilance 
Department (PVD) within 24 hours of discovery or notification of the event via 
recording in the eCRF. 
Refer to Section 12 for definitions, procedures and further information on AE 
reporting. 
9.2 
Special Circumstances 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. In cases where participants are not able to 
perform all protocol-defined assessments due to special circumstances, the 
investigator must discuss with the medical monitor potential mitigation approaches. 
For the duration of such special circumstances, the following measures may be 
implemented for enrolled participants: 


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x Participant and/or clinician-rated outcomes assessments may be done by 
videoconference, telephone call, or other means of virtual contact, if possible. 
x Visits may take place in a different location than defined in the protocol. If 
this is not feasible, then the visit may take place virtually with documentation 
of the means of communication (e.g., phone call or videoconference). 
x Biological samples may be collected and analyzed at a different location than 
defined in the protocol. Biological samples should not be collected if they 
cannot be processed in a timely manner or appropriately stored until 
shipping/processing. 
x If despite best efforts it is not possible to collect the biological samples or 
safety assessments (e.g., ECG or vital signs) within the interval predefined in 
the protocol (see Appendix 1), then the interval may be extended up to a 
maximum length of 14 days. 
x If despite best efforts safety assessment cannot be performed, the investigator 
must review the benefit-risk for participant continuation in the trial and record 
this in the medical records. 
The rationale (e.g., the specific limitation imposed by the special circumstances that 
led to the inability to perform the protocol-specified assessment) and outcome of the 
discussion with the medical monitor will be documented in the medical record. 
Information on how each visit was performed will be recorded in the eCRF. 
 


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10 
INVESTIGATIONAL MEDICINAL PRODUCT 
DISCONTINUATION AND WITHDRAWAL 
In accordance with the Declaration of Helsinki, the International Council for 
Harmonisation (ICH) Harmonised Guideline: Integrated Addendum to ICH E6(R1): 
Guideline for Good Clinical Practice (GCP) E6(R2), the FDA regulations relating to 
GCP and clinical trials, the EU Clinical Trials Directive, the EU GCP Directive 
and/or other applicable regulations, a participant has the right to withdraw from the 
trial at any time and for any reason, with no obligation to provide a reason, and 
without prejudice to his or her future medical care by the physician or at the 
institution. 
The participant must be permanently discontinued from IMP if any of the following 
apply: 
x Administrative decision by the investigator, GW, or a regulatory authority. 
x Withdrawal of participant consent. 
x Lost to follow-up. 
x Pregnancy. 
x QTcF ≥ 500 msec (average of 3 measurements). 
x Suicidal ideation or behavior of type 4 or 5 during the treatment period, as 
evaluated with the adult C-SSRS or based on investigator assessment. 
x Protocol deviation that is considered to potentially compromise the safety of 
the participant or validity of data collected. 
x ALT or AST > 3 u ULN with the appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(> 5%). 
x ALT or AST > 8 u ULN. 
x ALT or AST > 5 u ULN for more than 2 weeks. 
x ALT or AST > 3 u ULN and (TBL > 2 u ULN or INR > 1.5). 
Note: Prior to treatment discontinuation for the transaminase elevations noted 
above, the investigator may choose to confirm the transaminase elevations by 
repeating the following laboratory tests within 24 to 48 hours: ALT, AST, TBL, 
INR, % eosinophils, gamma-glutamyl transferase (GGT), and alkaline 
phosphatase. Should the above transaminase elevation criteria be confirmed, 
the participant must permanently discontinue IMP. In cases where 


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transaminase elevation IMP discontinuation criteria are not met or 
confirmed, the dose of a concomitant medication with known hepatotoxicity 
may be reduced. 
Should a participant request or decide to withdraw from the trial, all efforts must be 
made to complete and report the observations as thoroughly as possible up to the date 
of withdrawal. Participants withdrawing due to an AE should be followed up 
according to Section 12.7. All information should be reported on the applicable eCRF 
pages. A safety follow-up visit should take place 2 weeks after last dose of IMP. If 
withdrawing participants decline to give a reason for withdrawal of consent, the 
investigator must respect the participant’s wishes. 
 


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11 
URGENT SAFETY MEASURES 
The sponsor and investigator may take appropriate urgent safety measures in order to 
protect the participants of a clinical trial against any immediate hazard to their health 
or safety. If such measures are taken by the investigator, they must notify GW 
immediately or at least within 24 hours of awareness. GW will report urgent safety 
measures to regulatory authorities by telephone within 24 hours of awareness, 
wherever possible, and will provide a written report to the regulatory authorities and 
IRB/IEC within 3 days. 


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12 
ADVERSE EVENT REPORTING 
12.1 
Definitions 
12.1.1 
Adverse Event 
For the purposes of this trial an AE is defined as: 
Any new unfavorable/unintended signs/symptoms (including abnormal laboratory 
findings when relevant), or diagnosis or worsening of a pre-existing condition, which 
occurs following screening (Visit 1) and at any point up to the post-treatment, safety 
follow-up visit (Visit 8), which may or may not be considered to be related to the 
IMP. Any event that is the result of a trial procedure must be recorded as an AE. 
Surgical/investigational procedures are not AEs. The medical reason for the procedure 
is the AE. Elective hospitalizations for pre-trial existing conditions or elective 
procedures are not AEs. The exception may be if the participant has an AE during 
hospitalization that prolongs their scheduled hospital stay in which case it would be 
considered a SAE (refer Section 12.2). 
If reporting a fatal event, the SAE term should be the underlying cause of the death 
(e.g., disease or medical condition leading to death). 
12.1.2 
Investigator 
The term investigator refers to the trial PI or a formally delegated trial physician. 
12.2 
Serious Adverse Events 
During clinical investigations, AEs may occur which, if suspected to be IMP-related, 
might be significant enough to lead to important changes in the way the IMP is 
developed (e.g., change in dose, population, monitoring need, consent forms). This is 
particularly true for events that threaten life or function. Such SAEs will be reported 
promptly to regulatory authorities, applicable IRBs/IECs and investigators (expedited 
reporting) by GW. 
An AE must only be classed as serious, i.e., an SAE, when the event falls into 1 of the 
following criteria: 
x Results in death. 
x Is life-threatening. (The term “life-threatening” in the definition of “serious” 
refers to an event in which the participant was at risk of death at the time of 
the event; it does not refer to an event which, hypothetically, might have 
caused death if it were more severe.) 


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x Requires inpatient hospitalization or prolongation of existing hospitalization. 
(AEs requiring hospitalization should be considered serious. In general, 
hospitalization signifies that the participant has been detained [usually 
involving an overnight stay] at a hospital or emergency ward for observation 
and/or treatment which would not have been appropriate at the trial site. When 
in doubt as to whether hospitalization occurred or was necessary, the AE 
should be considered as serious.) 
x Results in persistent or significant disability/incapacity (disability is defined as 
a substantial disruption of a person’s ability to conduct normal life functions). 
x Is a congenital anomaly/birth defect. 
x Is medically significant. (Medical and scientific judgment should be exercised 
in deciding whether SAE reporting is appropriate in other situations. Important 
medical events may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require intervention 
to prevent one of the other outcomes listed in the definition above. These 
should also usually be considered serious. Examples of such events are 
intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in 
hospitalization, development of drug dependency or use of drugs of abuse, or 
positive COVID-19 test.) 
12.3 
Reporting Procedures for Serious Adverse Events 
All SAEs occurring during the trial must be reported to GW with any other supporting 
information and recorded in the AE section of the eCRF. Any ongoing SAEs should 
be followed up until resolution wherever possible. For all deaths, the working 
diagnosis or cause of death as stated on a death certificate, available autopsy reports 
and relevant medical reports should be sent to GW promptly. 
All SAEs must be recorded in the eCRF within 24 hours of discovery or 
notification of the event. GW PVD will be automatically notified that an SAE has 
been recorded. Any additional information required for a case (follow-up or 
corrections to the original case) will be requested by GW PVD through eCRF queries. 
The investigator should continue to document all AEs which occur up to the last 
formal follow-up observational period (Visit 8). If the investigator subsequently 
becomes aware of any deaths or a new IMP-related SAE after the last formal 
follow-up period of the trial, these should still be reported to the GW PVD. 


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Any other problem discovered after Visit 8 that is deemed to be an unexpected safety 
issue and is likely to have an impact on participants who have taken part in the trial 
must be treated as an SAE and reported to the GW PVD. Such post-trial SAEs do not 
need to be recorded on the participant’s eCRF if editing rights to the eCRF have been 
removed due to final trial data lock. GW PVD may request safety follow-up 
information after the final trial visit in order to investigate a potential safety issue. 
Contact details for the GW PVD are provided at the front of the site files for all trial 
sites. 
12.4 
Pregnancy 
Any participant, or participant’s partner, who has become pregnant whilst receiving 
IMP, or within 90 days of last dose of IMP, must be reported to the GW PVD. Where 
possible the investigator should provide the outcome of the pregnancy. 
All pregnancies must be recorded in the eCRF within 24 hours of becoming aware. 
GW PVD will be automatically notified that a pregnancy has been recorded. Any 
additional information required for a case (follow-up or corrections to the original 
case) will be requested by GW PVD through eCRF queries. 
The investigator is not obliged to actively monitor for any pregnancies that commence 
more than 90 days after the final dose of IMP. However, if the investigator becomes 
aware of a new pregnancy outside this time limit then they should report it as above. 
The GW PVD will follow-up for all pregnancy outcomes. 
12.5 
Causality Assessment 
Causality assessment is required for all AEs and SAEs. Causality assessment must 
only be assigned by the investigator. All cases judged as having a reasonable 
suspected causal relationship to the IMP must be reported as such. The expression 
“reasonable causal relationship” is meant to convey in general that there are facts 
(evidence) or arguments to suggest a causal relationship. 
The following question which must be answered by the investigator for all AEs is 
used to capture the reasonable causal relationship of an event to the IMP: 
“In your opinion is there a plausible relationship to the IMP?” The answer is either 
“yes” or “no”. 
Events that start before the first dose of IMP (pre-treatment) should be considered as 
not causally related. Where a pre-treatment event worsens in severity following the 
first dose of IMP, a new event record should be entered into the eCRF. 


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Considering the explanation given above, investigators are strongly encouraged to 
express their opinion on what the cause of an AE might be. For individual 
participants, the investigator is usually in the best position to assess the underlying 
suspected cause of an AE. For all AEs and especially SAEs, it is important that the 
investigator assess not only the possible role of the IMP but also other potential 
contributing factors. Factors for consideration of the underlying cause may include: 
x Medical history. 
x Lack of efficacy/worsening of treated condition. 
x Concomitant or previous treatment. 
x Withdrawal of IMP. 
x Protocol-related procedure. 
12.6 
Reporting Procedures for All Adverse Events 
All AEs (including SAEs) occurring during the trial will be reported on the running 
logs in the AE section of the eCRF. This includes all events from the time following 
screening (Visit 1) up to and including the post-trial follow-up visit (Visit 8), whether 
attributed to IMP or not and observed by the investigator or participant. 
The following information will need to be provided for all AEs: 
A) Adverse Event (Diagnosis or Syndrome if Known, or Signs and Symptoms) 
Where the investigator cannot determine a diagnosis, signs or symptoms should be 
recorded in the AE section of the eCRF. Once a diagnosis has been determined the 
AE section of eCRF must be updated to reflect the diagnosis in replacement of the 
original symptoms. In circumstances where only a provisional diagnosis is possible 
(working diagnosis), the eCRF must be updated to reflect the provisional diagnosis in 
replacement of the original symptoms. In some circumstances it may be relevant for 
the investigator to include the symptoms alongside the diagnosis in the verbatim event 
description. However, the diagnosis (full or provisional) should be clearly stated, e.g., 
fever and malaise due to respiratory tract infection. 
B) Adverse Event Start Date and Stop Date 
The start and stop dates of the event must be provided. All AEs require these fields to 
be completed in full. Partial dates or missing dates are not normally acceptable and 
significant effort must be undertaken to obtain any unknown information. If a precise 
date is not known an estimated date should be provided instead. When a complete 
date cannot be given, record as much information as possible (i.e., month and year or, 


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in exceptional circumstances, just year). When the actual start date becomes known 
the eCRF must be updated to replace the previously recorded date. 
C) Outcome 
The outcome of the event must be recorded accurately and classified as either: 
x Fatal. 
x Not recovered/Not resolved. 
x Recovered/Resolved. 
x Recovered/Resolved with sequelae. 
x Recovering/Resolving. 
x Unknown. 
D) Severity 
When describing the severity of an AE the terms mild, moderate, or severe should be 
used (see below). Clinical judgment should be used when determining which severity 
applies to any AE. 
If the severity of an AE fluctuates day-to-day, for example., a headache or 
constipation, the change in severity should not be recorded each time. Instead, only 
the worst observed severity should be recorded with AE start and stop dates relating 
to the overall event duration, regardless of severity. 
A severe AE is not the same as an SAE. For example, a participant may have severe 
vomiting, but the event does not result in any of the SAE criteria above. Therefore, it 
should not be classed as serious. The severity of an AE will be recorded as 1 of the 
following: 
x Mild: easily tolerated, does not interfere with normal daily activities, does not 
require intervention. 
x Moderate: causes some interference with daily activities; minimal, local or 
non-invasive intervention indicated. 
x Severe: daily activities limited or completely halted; intervention indicated. 
E) Causality 
Refer to Section 12.5 above. 


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F) Action Taken with Investigational Medicinal Product 
This question refers to the action taken with the IMP due to an AE. The action with 
the IMP must be classed as: 
x Dose increased. 
x Dose not changed. 
x Dose rate reduced. 
x Dose reduced. 
x Drug interrupted. 
x Drug withdrawn. 
x Not applicable. 
x Unknown. 
12.7 
Follow-up Procedures for Adverse Events 
The investigator may be asked to provide follow-up information to the GW PVD for 
any AEs reported or during the investigation of potential safety issues. Such requests 
for additional safety information may occur post Visit 8, after the trial. 
AEs considered related to the IMP by the investigator or the sponsor should be 
followed up until resolution or the event is considered stable. 
It will be left to the investigator’s clinical judgment if an AE is of sufficient severity 
to require the participant’s removal from treatment. A participant may also voluntarily 
withdraw from treatment due to what he or she perceives as an intolerable AE. 
Further details of withdrawal are presented in Section 10. If either of these occurs, the 
participant must undergo an EOT assessment and be given appropriate care under 
medical supervision until symptoms cease or the condition becomes stable. If a safety 
concern is identified following withdrawal of a participant, GW may contact the 
investigator for additional follow-up information. 
12.8 
Potential Cases of Drug-induced Liver Injury 
All investigational sites are required to submit to the GW PVD the laboratory results 
for any participant after randomization that meets the criteria for the selected 
laboratory parameters as follows: 


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x Serum ALT or AST > 3 u ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (> 5%). 
x ALT or AST > 8 u ULN. 
x ALT or AST > 5 u ULN for more than 2 weeks. 
x ALT or AST > 3 u ULN and (TBL > 2 u ULN or INR > 1.5). 
These reports must be sent to the GW PVD via email (see Appendix 2) within 
24 hours of becoming aware of the results. In addition, please send a copy of the 
participant’s baseline laboratory results with all reports to the GW PVD. 
Abnormal values in AST and/or ALT concurrent with abnormal elevations in TBL 
that meet the criteria outlined above are considered potential cases of drug-induced 
liver injury and will be considered as protocol-defined criteria for treatment 
discontinuation and important medical events. The investigator will arrange for the 
participant to return to the investigational site as soon as possible (within 
24 to 48 hours of notice of abnormal results) for repeat assessment of ALT, AST, 
TBL, alkaline phosphatase, and GGT, detailed history and physical examination. 
Participants should be followed in this way until all abnormalities have normalized (in 
the investigator’s opinion) or returned to the baseline state. However, if the above 
transaminase elevation criteria are confirmed by the first set of follow-up laboratory 
tests, the participant must be withdrawn from the trial. 
Elevations in ALT or AST > 3 × ULN or TBL > 2 × ULN alone are not considered 
potential cases of drug-induced liver injury, but will be followed as detailed above, 
within 72 hours’ notice of abnormal results. If the participant cannot return to the 
investigational site, repeat assessments may be done at a local laboratory and the 
results sent to GW PVD. 
12.9 
Notification of Safety Information to Investigators, Regulatory 
Authorities and Institutional Review Board or Independent 
Ethics Committee 
In accordance with the EU Clinical Trials Directive, relevant parts of the FDA Code 
of Federal Regulations and any national regulations, GW will inform investigators, 
regulatory authorities and relevant IRBs/IECs of all relevant safety information. This 
will include the reporting of relevant SAEs and all suspected unexpected serious 
adverse reactions (SUSARs). This information will be provided through 2 sources: 


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1. Investigator’s Brochure (IB)42: a compilation of the clinical and non-clinical 
safety data available on the IMP that is relevant to the trial. The IB is updated 
annually or when important new safety information becomes available. 
2. Council for International Organizations of Medical Sciences (CIOMS) reports: 
these reports are issued every time a SUSAR is reported to GW. They provide 
information on individual case reports and are sent to all the regulatory 
authorities, the relevant central ECs which have approved the trial and 
investigators. As required, the investigator should notify their regional 
IRBs/IECs of SAEs or SUSARs occurring at their site and other AE reports, 
i.e., CIOMS reports and any additional safety documentation received from 
GW, in accordance with local procedures. 
In the US, investigators are normally required to report promptly to their IRBs all 
unanticipated problems involving risks to participants, or others, including AEs that 
should be considered unanticipated problems. Based on current FDA guidance the 
following clarification is provided in determining what constitutes an unanticipated 
problem: 
In general, an AE observed during the conduct of a trial should be considered an 
unanticipated problem involving risk to participants and reported to the IRB, only if it 
were unexpected, serious, and would have implications for the conduct of the trial 
(e.g., requiring a significant, and usually safety-related, change in the protocol such as 
revising inclusion/exclusion criteria or including a new monitoring requirement, 
informed consent, or IB). An individual AE occurrence ordinarily does not meet these 
criteria because, as an isolated event, its implications for the trial cannot be 
understood. 
The FDA guidance states that, accordingly, to satisfy the investigator’s obligation to 
notify the IRB of unanticipated problems, any investigators participating in a multisite 
trial may rely on the sponsor’s assessment and provide to the IRB a report of the 
unanticipated problem prepared by the sponsor. 
GW will inform investigators, regulatory authorities and relevant IRBs/IECs of any 
safety issues or case reports that are considered to be unanticipated and provide such 
reports as mentioned above. It should be noted that a single SUSAR report notified to 
investigators in the trial does not necessarily constitute an unanticipated problem 
unless identified by GW in the submission cover letter. 
As a minimum, the recipient will be sent all of the above and relevant updates 
between the period from ethical approval and final database lock. 


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13 
STATISTICAL CONSIDERATIONS 
Further details of the proposed statistical analysis will be documented in a SAP, 
which will be finalized prior to unblinding of the trial. Any deviations from the 
original SAP will be described in the final clinical study report. 
13.1 
Sample Size, Power, and Significance Levels 
Approximately 366 participants will be randomized following the placebo run-in 
period to receive 1 of 2 dose levels of GWP42003-P (150 mg b.i.d. or 500 mg b.i.d.) 
or dose matching volume of placebo (150 mg b.i.d. and 500 mg b.i.d.) on a 
2:2:1:1 basis. The placebo groups will be pooled for the analyses of efficacy. 
Assuming a common standard deviation of 11.0 and using a 2-sided hypothesis test at 
a 0.05 α-level, a total sample size of 366 participants (122 participants per active dose 
group and 61 participants per placebo group) will provide 80% power to detect a 
significant result assuming a true treatment difference of −4.32 points on the 
PANSS-T score in change from baseline to EOT between 500 mg b.i.d. of 
GWP42003-P and placebo. This allows for a 15% drop-out rate, with a minimum of 
309 participants needed to complete the trial. Depending on the drop-out rate, during 
the trial, the number of randomized participants may be increased to ensure a 
minimum of 309 evaluable participants at Week 12. 
At least 366 participants will be randomized to receive dose matching volume of 
placebo during the placebo run-in period (150 mg b.i.d. and 500 mg b.i.d. in a 
1:1 ratio), thereafter randomized to receive GWP42003-P (150 mg b.i.d. or 
500 mg b.i.d.) or dose matching volumes of placebo at a 2:1 ratio within each dose 
level. 
13.2 
Interim Analysis 
Unblinded interim evaluations, including sample size reassessment, may be 
performed as part of an internal Data Monitoring Committee (DMC) review (see 
Section 14). 
Bayesian analysis of the key variables of interest may be performed to evaluate the 
probability that GWP42003-P is different than placebo. Details of the evaluation 
criteria will be provided in a separate SAP or simulation plan. 
13.3 
Analysis Sets 
 
 
 
PI


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The following analysis sets will be used for the statistical analysis: 
Full Analysis Set 
x All participants who are randomized and receive at least 1 dose of IMP in the 
trial will be included and analyzed according to their randomized treatment 
arm. 
x The full analysis set (FAS) is the primary analysis set for all efficacy 
endpoints. 
Safety Analysis Set 
x All participants who receive at least 1 dose of IMP in the trial will be included 
and analyzed according to the treatment received. Only participants for whom 
it has been confirmed that they did not take any IMP will be excluded from 
this safety analysis set. This analysis set will be used to report the safety data. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PI
PI


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Analysis sets will be identified prior to the unblinding of the trial data. 
13.3.1 
Protocol Deviations 
Protocol deviations will be listed and reasons for exclusion from the analysis sets 
(for major protocol deviations) will be summarized. 
13.4 
General Considerations 
Unless stated otherwise, continuous variables will be summarized showing the 
number of non-missing values (n), mean, SD, median, minimum, and maximum, and 
categorical variables will be summarized showing the number and percentage of 
participants falling in each category. Unless otherwise specified, tables will be 
summarized by randomized treatment group. 
For clinic visit-based endpoints (unless otherwise specified), baseline is defined as the 
last record or measure collected prior to the first dose of IMP in the treatment period. 
13.5 
Accountability and Background Characteristics 
13.5.1 
Enrolment and Disposition 
All participants (screened, randomized, withdrawn, etc.,) will be accounted for in the 
enrolment and disposition summary tables. 
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13.5.2 
Baseline and Demographic Characteristics 
Age, sex, race (as per local data protection laws in each specific country), ethnic 
origin, and any other demographic or baseline characteristics including the age of first 
use of cannabis, duration since first regular use (years), currently using/used cannabis 
within the last month (yes, no), regularly using cannabis once per week or more (yes, 
no), and most common route of current administration (smoked, vaped, oral) will be 
summarized by treatment arm, using appropriate summary statistics. 
There will be no formal comparison of baseline data; that is, no statistical hypothesis 
testing. 
13.5.3 
Medical History 
Previous and current medical conditions (including details of schizophrenia and other 
comorbid psychiatric disorders) will be summarized by system organ class (SOC) by 
treatment arm. 
13.5.4 
Concomitant Medication 
Concomitant medications (including antipsychotic medication treatments for 
schizophrenia) taken prior to and during the trial will be summarized separately by 
treatment arm, medication class, and active ingredients. 
13.6 
Endpoints and Statistical Methods 
Statistical hypothesis testing will be performed on the efficacy and exploratory 
endpoints as appropriate. Each endpoint will have 2 comparisons against placebo 
(150 mg b.i.d. GWP42003-P and 500 mg b.i.d. GWP42003-P versus placebo). 
All safety data will be summarized using appropriate statistical methods. 
13.6.1 
Efficacy Analysis 
The change from baseline to Week 12 in PANSS-T, PANSS-P, PANSS-N, and 
PANSS-G scores will be summarized separately by treatment arm for each visit. 
Associated baseline scores will be taken as the last corresponding measurement prior 
to the first dose of IMP in the treatment period (e.g., Visit 3). 
The change from baseline in each score will be analyzed separately using a 
mixed-effects repeated measures (MMRM) model. The corresponding model will 
include stratification factors, associated baseline, visit, treatment arm, visit by 
treatment arm interaction and visit by associated baseline interaction as fixed effects, 
and visit repeated within each participant as a repeated effect. An unstructured 
covariance matrix will be used to estimate the variance-covariance structure within 


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participants across time points. If convergence is not obtained, then other covariance 
structures to be used will be specified in the SAP. Objective criteria for assessing 
normality assumptions and proposed alternative analyses will be specified in the SAP. 
From this analysis the least squares (LS) mean estimates for each treatment arm at 
each visit, along with the standard error and 95% confidence intervals (CIs) will be 
presented separately for each endpoint. In addition, estimates of the treatment 
difference at each visit will be presented along with standard errors of the difference 
and 95% CIs. The primary comparison for each endpoint is the estimate of the 
treatment difference at Week 12. 
For participants who complete the trial, regardless of whether IMP is discontinued or 
not, the visit effect used in the analysis will correspond to the associated score at each 
trial visit (e.g., Visits 4, 5, 6, and 7). However, participants who withdraw from the 
trial are required to complete the procedures at Visit 7 at the time of withdrawal. For 
these participants, Visit 7 data will be assigned to the nearest post-baseline visit (for 
which the assessment is scheduled to be performed), based on the trial day of the visit. 
Further details will be specified in the SAP. 
The numeric values of CGI-S and CGI-I assessments will be analyzed separately 
using similar model approaches as for PANSS-T. For CGI-S, baseline score will be 
included as a covariate. Both values for the original categorical scale and the 
converted numerical scale at each visit (including change from baseline for the CGI-S 
numerical scale) will be summarized using standard summary statistics. 
Full details of the efficacy analyses and any further analyses deemed appropriate will 
be provided in the SAP. 
No formal adjustment of statistical significance for multiple testing on multiple 
endpoints will be performed, although such multiplicity should be allowed for when 
interpreting the results. 
 
 
 
 
 
 
 
 
 
 
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13.6.4 
Safety 
The following safety endpoints are used to support the safety objective and will be 
evaluated based on Statistical Analysis System (SAS®). Each endpoint will be 
compared with placebo at each dose level as described in the following sections: 
x AEs. 
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x Clinical laboratory parameters. 
x Vital signs. 
x Physical examination procedures. 
x ECG. 
x Suicidality. 
x Extrapyramidal symptoms as assessed by ESRS. 
x CDSS. 
All safety endpoints will be summarized by treatment received using appropriate 
statistical methods. 
13.6.4.1 
Treatment Compliance and Extent of Treatment Exposure 
Treatment compliance and exposure to treatment will be summarized. 
13.6.4.2 
Adverse Events 
Adverse events will be coded according to the Medical Dictionary for Regulatory 
Activities dictionary. 
A treatment-emergent adverse event (TEAE) is one that started, or worsened in 
severity or seriousness, following the first dose of IMP. 
Descriptive presentations of TEAEs will be given by preferred term and SOC for the 
safety analysis set. The number of participants reporting at least 1 TEAE will be 
provided. AEs will be summarized in terms of the number of participants with at least 
1 event (N) and the percentage of participants with at least 1 event (%). 
The following summaries will be produced as a minimum: 
x All-causality TEAEs. 
x Treatment-related AEs. 
x All-causality TEAEs by maximal severity. 
x All-causality serious TEAEs. 
x Treatment-related serious TEAEs. 
x TEAEs reported as leading to permanent cessation of IMP. 
x Fatal TEAEs. 


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In the presentation of safety data, data from the GWP42003-P dose groups will be 
presented separately and compared with placebo. This will allow the possibility to 
explore any effects of the dose of IMP on safety endpoints. 
Supportive summaries of ADRs will be presented. 
13.6.4.3 
Vital Signs, 12-lead Electrocardiogram, Physical 
Examination, and Other Safety Data 
Vital signs, ECG, physical examination, CDSS, and extrapyramidal symptoms as 
assessed by the ESRS 45-item total score will be summarized at each time point using 
appropriate summary statistics. Changes in body weight, BMI, waist circumference, 
vital signs, ECG parameters, and the ESRS 45-item total score from baseline will be 
summarized by visit. 
13.6.4.4 
Clinical Laboratory Data 
Clinical laboratory data will be summarized at screening, baseline, and at each time 
point during the treatment period using appropriate summary statistics. Categorical 
shift tables will be presented, showing the numbers of participants with values outside 
the normal range. Change from baseline will also be summarized by visit. 
13.6.4.5 
Suicidality 
C-SSRS data will be summarized and listed as appropriate. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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14 
DATA MONITORING COMMITTEE 
An internal DMC will be setup for unblinded data review. The DMC will not include 
any members of the study team. Operations and constitution of the DMC will be 
detailed in a separate charter. 


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15 
REGULATORY AND ETHICAL OBLIGATIONS 
15.1 
Declaration of Helsinki 
The investigator will ensure that this trial is conducted in full conformity with the 
current version and subsequent amendments of the Declaration of Helsinki, the ICH 
Harmonised Guideline: Integrated Addendum to ICH E6(R1): Guideline for GCP 
E6(R2), the EU Clinical Trials Directive, the EU GCP Directive, and the clinical trial 
regulations adopting European Commission Directives into national legislation. 
15.2 
Informed Consent 
An initial master ICF will be prepared by GW and provided to the investigator, who 
will tailor this for their site by adding the site’s contact details and by using headed 
paper. The GW clinical manager will communicate updates to the template by letter. 
The written informed consent document should be prepared in the language(s) of the 
potential participant population. 
Before a participant’s involvement in the trial, the investigator or authorized delegate 
is responsible for obtaining written informed consent from the participant after 
adequate explanation of the aims, methods, anticipated benefits and potential hazards 
of the trial and before any trial-specific procedures are performed or any 
participant-related data are recorded for the trial. The participant must have ample 
time to consider the information provided before giving written consent. More 
specific definitions of ‘ample time’ may be in force if required by IRBs/IECs or local 
regulations. 
The acquisition of informed consent must be documented in the participant’s medical 
records and the ICF must be signed and personally dated by the participant and by the 
person who conducted the informed consent discussion. Informed consent should be 
taken in accordance with the guidance provided in ICH E6 by an appropriately trained 
and delegated site staff member. A physician should be available to answer any 
questions from the participant should they arise. The original signed ICF should be 
retained and a copy provided to the participant. 
15.3 
Institutional Review Board/Independent Ethics Committee 
A copy of the protocol, proposed ICF, master ICF, other participant information 
material, any proposed advertising material and any further documentation requested 
must be submitted to the IRB/IEC for written approval. GW must receive a copy of 
the written approval of the appropriate version of the protocol and ICF before 
recruitment of participants into the trial and shipment of IMP. 


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The investigator must submit and, where necessary, obtain approval from the 
IRB/IEC for all subsequent protocol amendments and changes to the informed 
consent document. The investigator must notify the IRB/IEC of deviations from the 
protocol, SAEs occurring at the site and other AE reports received from GW, in 
accordance with local procedures. 
The investigator will be responsible for obtaining ongoing IRB/IEC approval/renewal 
throughout the duration of the trial. Copies of the investigator’s reports and the 
IRB/IEC continuance of approval must be sent to GW. 
15.4 
Pre-trial Documentation Requirements 
The investigator is responsible for forwarding the following documents to GW for 
review before allowing any participants to consent for entry into the trial: 
x Signed and dated protocol signature page. 
x Copy of the IRB/IEC approval of the protocol, ICF (including version number 
and date) and other participant information material. 
x Up to date curricula vitae and medical licenses (as per local regulations) of the 
PI and all sub-investigators. 
x The IRB/IEC composition and/or written statement of the IRB/IEC in 
compliance with the FDA regulations relating to GCP and clinical trials, the 
EU Clinical Trials Directive, the EU GCP Directive, or the ICH Harmonised 
Guideline: Integrated Addendum to ICH E6(R1): Guideline for GCP E6(R2) 
where the EU Clinical Trials and GCP Directives do not apply. 
x Signed and dated laboratory normal ranges and documentation of laboratory 
certification (or equivalent) unless using central laboratory arranged by GW. 
x Signed and dated clinical trial agreement (including participant/investigator 
indemnity insurance and financial agreement). 
x Form FDA 1572, if required. 
x Completed financial disclosure statements for the PI and all sub-investigators, 
if relevant. 
GW will ensure that the site is informed of when screening of participants can 
commence. 


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15.5 
Participant Confidentiality 
The investigator must ensure that the participant’s anonymity is maintained. In the 
eCRFs or other documents submitted to GW, participants should be identified by their 
initials and race (if allowed per local regulations) and their trial screening number 
only. Documents that are not for submission to GW, e.g., signed ICFs, should be kept 
in strict confidence by the investigator. 
In compliance with the FDA regulations relating to GCP and clinical trials, and the 
EU Clinical Trials Directive/ICH Harmonised Guideline: Integrated Addendum to 
ICH E6(R1): Guideline for GCP E6(R2), it is required that the investigator and 
institution permit authorized representatives of the company, the regulatory 
authorities and the IRB/IEC have direct access to review the participant’s original 
medical records for verification of trial-related procedures and data. Direct access 
includes examining, analyzing, verifying, and reproducing any records and reports 
that are important to the evaluation of the trial. The investigator is obligated to inform 
the participant that his/her trial-related records will be reviewed by the above-named 
representatives without violating the confidentiality of the participant. 
All information concerning the IMP and operations of GW such as patent 
applications, formulae, manufacturing processes, basic scientific data or formulation 
information supplied to the investigator by the company and not previously published 
is considered confidential by the company and shall remain the sole property of the 
company. The investigator will agree to use this information only in accomplishing 
the trial and will not use it for any other purposes without the written consent of the 
company. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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16 
ADMINISTRATIVE AND LEGAL OBLIGATIONS 
16.1 
Protocol Amendments and End of Trial or Termination 
Protocol amendments must be made only with the prior approval of GW. Agreement 
from the investigator must be obtained for all protocol amendments and amendments 
to the informed consent document. The IRB/IEC and regulatory authorities must be 
informed of all amendments and give approval for any substantial amendments. 
Amendments for administrational changes can be submitted to the IRB/IEC for 
information only. The investigator must send a copy of the approval letter from the 
IRB/IEC to GW. 
Both GW and the investigator reserve the right to terminate the trial, according to the 
clinical trial agreement. The investigator must notify the IRB/IEC in writing of the 
trial’s completion or ET and send a copy of the notification to GW. 
16.2 
Trial Documentation and Storage 
The investigator must maintain a list of appropriately qualified persons to whom 
he/she has delegated trial duties. All persons authorized to make entries in and/or 
corrections to eCRFs will be included on the GW Delegation of Authority and 
Signature form. 
Source documents are original documents, data and records containing all 
protocol-specified information from which the participant’s eCRF data are obtained. 
These include, but are not limited to, hospital records, clinical and office charts, 
laboratory and pharmacy records, diaries, microfiches, radiographs, and 
correspondence. A source data verification plan, identifying the source for each data 
point at each site, will be agreed with each site prior to participant recruitment. In the 
rare situations of data being recorded directly into the eCRF in error, then the source 
data from the eCRF should be transcribed into the participant’s notes with appropriate 
signature and date to provide a full audit trail. 
The investigator and trial staff are responsible for maintaining a comprehensive and 
centralized filing system of all trial-related, essential documentation (as outlined in 
ICH Harmonised Guideline: Integrated Addendum to ICH E6(R1): Guideline for GCP 
E6[R2], Section 8.2), suitable for inspection at any time by representatives from GW 
and/or applicable regulatory authorities. Elements should include: 


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x Participant files containing completed eCRFs, ICFs, and supporting copies of 
source documentation. 
x Trial files containing the protocol with all amendments, IB, copies of pre-trial 
documentation (see Section 15.4) and all correspondence to and from the 
IRB/IEC and GW. 
x Enrolment log of all participants who consented to take part in the trial. 
x Screening and recruitment log of all participants screened and whether they 
were recruited into the trial or not (i.e., randomized and/or dosed with IMP). 
x Proof of receipt, IMP accountability record, return of IMP for destruction, 
final IMP reconciliation statement and all drug-related correspondence. 
In addition, all original source documents supporting entries in the eCRFs must be 
maintained and be readily available. 
Following completion or termination of a clinical trial, GW will initiate proper 
archive of clinical trial-related documentation and electronic records generated by the 
investigator and/or GW. All clinical trial-related documents and electronic records 
will be retained within an archiving system for a period dependent upon need and for 
a minimum of 25 years. Essential documents must be retained until at least 2 years 
after the last approval of a marketing application in an ICH region and until there are 
no pending or contemplated marketing applications in an ICH region, or until at least 
2 years have elapsed since the formal discontinuation of clinical development of the 
IMP. These documents must be retained for a longer period, however, if required by 
the applicable regulatory requirements or if needed by GW. 
GW will inform the investigators for each site in writing of the need for record 
retention. No trial document may be destroyed without prior written agreement 
between GW and the investigator. Should the investigator wish to assign the trial 
records to another party or move them to another location, he/she must notify GW in 
writing of the new responsible person and/or the new location. 
16.3 
Trial Monitoring and Data Collection 
The GW representative and regulatory authority inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting (on-site or 
remotely) the facilities and, upon request, inspecting the various records of the trial, 
e.g., eCRFs and other pertinent data, provided participant confidentiality is respected. 
The GW trial monitor, or designee, is responsible for inspecting the eCRFs at regular 
intervals throughout the trial to verify adherence to the protocol, completeness, 


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accuracy and consistency of the data, and adherence to local regulations on the 
conduct of clinical research. The trial monitor must have (direct or remote) access to 
participant medical records and other trial-related records needed to verify the entries 
on the eCRFs. 
The investigator agrees to cooperate with the trial monitor to ensure that any problems 
detected in the course of these monitoring visits are resolved. 
To ensure the quality of clinical data across all participants and sites, a clinical data 
management review will be performed on participant data received at GW or a 
contract research organization (CRO). During this review, participant data will be 
checked for consistency, omissions, and any apparent discrepancies. In addition, the 
data will be reviewed for adherence to the protocol and FDA regulations, ICH 
Harmonised Guideline: Integrated Addendum to ICH E6(R1): Guideline for GCP 
E6(R2), and all other applicable regulatory requirements. To resolve any questions 
arising from the clinical data management review process, data queries and/or site 
notifications will be sent to the site for completion and then returned to GW or the 
CRO, as applicable. 
16.4 
Quality Assurance 
In accordance with the FDA regulations, EU Clinical Trials Directive/ICH 
Harmonised Guideline: Integrated Addendum to ICH E6(R1): Guideline for GCP 
E6(R2) and the sponsor’s audit plans, representatives from GW’s Clinical Quality 
Assurance Department may select this trial for audit. Inspection of site facilities, e.g., 
pharmacy, drug storage areas, laboratories, and review of trial-related records will 
occur to evaluate the trial conduct and compliance with the protocol, the EU Clinical 
Trials Directive/ICH Harmonised Guideline: Integrated Addendum to ICH E6(R1): 
Guideline for GCP E6(R2) and applicable regulatory requirements. 
16.5 
Compensation 
GW will indemnify the investigator and the trial site in the event of any claim in 
respect of personal injury arising due to a participant’s involvement in the trial, 
providing that the trial protocol has been adhered to. This would include claims 
arising out of or relating to the administration of the IMP or any clinical intervention 
or procedure provided for or required by the protocol to which the clinical trial 
participant would not otherwise have been exposed, providing there is no evidence of 
negligence on behalf of the investigator or their team. GW will not be liable for any 
claims arising from negligence on the part of the investigator or their team. 


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16.6 
Publication Policy 
GW recognizes that there is a responsibility under the regulatory guidelines to ensure 
that results of scientific interest arising from this clinical trial are appropriately 
published and disseminated. They will coordinate this dissemination and may solicit 
input and assistance from the chief/PIs. A summary of the results of this trial will be 
made available on http://www.clinicaltrials.gov and 
http://www.clinicaltrialsregister.eu/ (as applicable), as required by US and EU Law. 
The raw data from this trial may be obtained by the PIs or by their steering committee 
representatives on request. Should they wish, PIs are allowed to conduct their own 
analyses and are permitted to present such information along with methods and results 
of the clinical trial at symposia, national or regional professional meetings and to 
publish it in theses or dissertations. 
All publications, e.g., manuscripts, abstracts, oral/slide presentations or book chapters 
based on this trial, must be submitted to the GW Medical Writing Department and, as 
applicable, GW Publication Committee for corporate review before release. To ensure 
adequate time for GW to make comments and suggestions where pertinent, all such 
material should be submitted to them at least 60 days prior to the date for submission 
for publication, public dissemination, or review by a publication committee. The PIs 
must then incorporate all reasonable comments made by GW into the publication. 
GW also reserves the right to delay the submission of such information by a period of 
up to 6 months from the date of first submission to them in order to allow them to take 
steps to protect proprietary information where applicable. 
16.7 
Intellectual Property Rights 
All intellectual property rights owned by or licensed to either GW or the PIs, other 
than those arising from the clinical trial, will remain their property. All intellectual 
property rights arising out of the clinical trial will vest in or be exclusively licensed to 
GW and, as such, the PI must promptly disclose all knowledge to GW and refrain 
from using such knowledge without the prior written consent of GW. 
16.8 
Confidential Information 
GW and the PI must ensure that only personnel directly concerned with the trial are 
party to confidential information and that any information coming to either party 
about the other during the course of the trial must be kept strictly confidential and 
must not be disclosed to any third party or made use of without the prior written 
consent of the other. 


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14 Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs 
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15 Verma S, Subramaniam M, Abdin E, Poon LY, Chong SA. Symptomatic and 
functional remission in patients with first-episode psychosis. Acta Psychiatr 
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schizophrenia: effects of second generation antipsychotics. CNS Drugs. 
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17 Fusar-Poli P, Papanastasiou E, Stahl D, et al. Treatments of Negative Symptoms 
in Schizophrenia: Meta-Analysis of 168 Randomized Placebo-Controlled Trials. 
Schizophr Bull. 2015;41(4):892–9. 
18 Lang UE, Puls I, Muller DJ, Strutz-Seebohm N, Gallinat J. Molecular mechanisms 
of schizophrenia. Cell Physiol Biochem. 2007;20(6):687–702. 
19 Lisman JE, Coyle JT, Green RW, et al. Circuit-based framework for 
understanding neurotransmitter and risk gene interactions in schizophrenia. 
Trends Neurosci. 2008;31(5):234–42. 
20 GWOR10133 Study Report. Evaluation of Effects of Pure Cannabidiol (CBD 
Pure) on D-Amphetamine-induced Hyperlocomotion. Mar 2011. 
21 GWOR10151 Study Report. Evaluation of Effects of Pure Cannabidiol (CBD 
Pure) on D-Amphetamine-induced Hyperlocomotion. Mar 2011. 
22 Neill JC, Barnes S, Cook S, et al. Animal models of cognitive dysfunction and 
negative symptoms of schizophrenia: focus on NMDA receptor antagonism. 
Pharmacol Ther. 2010;128(3):419–32.  
23 GWOR1027 Study Report. Adjunctive Effect of Cannabidiol and 
Tetrahydrocannabivarin on Cataleptogenic Potential of Aripiprazole in Rats. Feb 
2009. 
24 Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide 
signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 
2012; 20;2:e94. 
25 McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an Adjunctive 
Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J 
Psychiatry. 2018;175(3):225–231. 
26 GWTX1562 Study Report: In Vitro Pharmacology Study of Several Compounds. 
December 2015. 
27 Turner SE, Williams CM, Iversen L, Whalley BJ. Molecular Pharmacology of 
Phytocannabinoids. Prog Chem Org Nat Prod. 2017;103:61–101. 
28 GWOR0873 Study Report. An in vitro evaluation of the effect of 
phytocannabinoids on NAAA. Jan 2013. 
29 GWOR0885 Study Report. An in vitro evaluation of the effect of 
phytocannabinoids on endocannabinoid uptake. Jan 2013. 
30 GWOR0861 Study Report. An in vitro evaluation of the effect of 
phytocannabinoids on FAAH. Jan 2013. 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
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31 GWOR0849 Study Report. An in vitro evaluation of the effect of 
phytocannabinoids on MAGL & DAGL. Jan 2013. 
32 Ibeas Bih C, Chen T, Nunn AV, Bazelot M, Dallas M, Whalley BJ. Molecular 
Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics. 
2015;12(4):699-730. 
33 Ryberg E, Larsson N, Sjögren S, et al. The orphan receptor GPR55 is a novel 
cannabinoid receptor. Br J Pharmacol. 2007;152(7):1092–101. 
34 Rosenberg E, Bazelot M, Salah A, et. al. Cannabidiol (CBD) exerts anti-epileptic 
properties by targeting the LPI-GPR55 signaling system potentiated by seizures. 
American Epilepsy Society (AES) 2018 Annual Meeting. New Orleans. 
35 Epidiolex Prescribing Information. Revised October 2020. 
https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Info
rmation.pdf (accessed 18 March 2021) 
36 Clinical Trial Facilitation Group: Recommendations related to contraception and 
pregnancy testing in clinical trials.  September 2014. 
37 Chouinard G, Margolese HC. Manual for the Extrapyramidal Symptom Rating 
Scale (ESRS). Schizophr Res. 2005;76(2-3):247–65. 
38 Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International 
Neuropsychiatric Interview (M.I.N.I.): the development and validation of a 
structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin 
Psychiatry. 1998;59 Suppl 20:22–33;quiz 34–57. 
39 Kim SW, Kim SJ, Yoon BH, et al. Diagnostic validity of assessment scales for 
depression in patients with schizophrenia. Psychiatry Res. 2006;144(1):57–63. 
40 Addington D, Addington J, Maticka-Tyndale E, Joyce J. Reliability and validity 
of a depression rating scale for schizophrenics. Schizophr Res. 1992;6(3):201–8. 
41 Wilkinson G, Hesdon B, Wild D, et al. Self-report quality of life measure for 
people with schizophrenia:the SQLS. Br J Psychiatry. 2000;177:42–6.  
42 Investigator's Brochure: CBD Medicine. GW Pharma Ltd. Edition 11. Sep 2018. 
 
 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
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Clinical Protocol Template (Phase 2–4) 
V1, 24Sep15 
Clinical Protocol Global V2 Based on Clinical Protocol V1 11Nov2019 
 APPENDIX 1 
SCHEDULE OF ASSESSMENTS 
Period 
Screening 
Period 
Placebo  
Run-in  
Period 
Treatment  
Period 
Safety Follow-up 
Period 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
EOT/ETa 
8 
Telephone call 
Week 
−6 
−2 
 
2 
4 
8 
12 
14 
Day 
−42 to −15  
−14  
1 (Baseline) 
15 
29 
57 
85 
99 
Visit Window (Days) 
 
 
+3 
±3 
±3 
±3 
±3 
±3 
Informed consent 
X 
 
 
 
 
 
 
 
Eligibility criteria 
Xp 
 
X 
 
 
 
 
 
Placebo-response training videob 
 
X 
X 
 
 
 
X 
 
Demographics 
X 
 
 
 
 
 
 
 
Cannabis use surveyc 
X 
X 
X 
X 
X 
X 
X 
 
Medical history 
X 
 
 
 
 
 
 
 
Psychiatric history 
X 
 
 
 
 
 
 
 
Physical examinationd 
X 
 
X 
 
 
 
X 
 
Body weight, BMI, waist circumference and heighte 
X 
 
X 
X 
X 
X 
X 
 
Vital signsf, g 
X 
X 
X 
X 
X 
X 
X 
 
ECGf, h 
X 
 
X 
 
 
 
X 
 
Chemistry 
X 
 
X 
 
X 
 
X 
 
Hematology 
X 
 
X 
 
X 
 
X 
 
Serologyi 
X 
 
 
 
 
 
 
 
PK blood samplingj 
X 
 
 
X 
 
 
Xq 
 
Biomarker sampling 
 
 
X 
 
 
 
X 
 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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Page 100 of 104 
Clinical Protocol Template (Phase 2–4) 
V1, 24Sep15 
Clinical Protocol Global V2 Based on Clinical Protocol V1 11Nov2019 
Period 
Screening 
Period 
Placebo  
Run-in  
Period 
Treatment  
Period 
Safety Follow-up 
Period 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
EOT/ETa 
8 
Telephone call 
Week 
−6 
−2 
 
2 
4 
8 
12 
14 
Day 
−42 to −15  
−14  
1 (Baseline) 
15 
29 
57 
85 
99 
Visit Window (Days) 
 
 
+3 
±3 
±3 
±3 
±3 
±3 
Pharmacogenomic DNA sampling 
 
 
X 
 
 
 
 
 
Pharmacogenomic RNA sampling 
 
 
X 
 
 
 
X 
 
Urinalysis 
X 
 
X 
X 
 
X 
X 
 
Drug screenk 
X 
 
X 
 
 
 
X 
 
Pregnancy test (for WOCBP) 
X 
 
X 
 
X 
X 
X 
 
ESRSl 
X 
 
X 
X 
X 
X 
X 
 
C-SSRS 
X 
X 
X 
X 
X 
X 
X 
 
MINI for Psychotic Disorders Studies 
X 
 
 
 
 
 
 
 
PANSSm 
X 
X 
X 
X 
X 
X 
X 
 
CGI-S 
X 
X 
X 
X 
X 
X 
X 
 
CGI-I 
 
 
 
X 
X 
X 
X 
 
PGIC 
 
 
X 
X 
X 
X 
X 
 
CDSS 
 
X 
X 
 
 
 
X 
 
BACS 
X 
 
X 
 
 
 
X 
 
SQLS 
 
X 
X 
 
 
 
X 
 
BAS-MPsQ 
 
X 
 
 
 
X 
 
 
EXP-MPsQ 
 
 
X 
 
 
 
 
 
PER-MPsQ 
 
X 
 
 
 
 
 
 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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Page 101 of 104 
Clinical Protocol Template (Phase 2–4) 
V1, 24Sep15 
Clinical Protocol Global V2 Based on Clinical Protocol V1 11Nov2019 
Period 
Screening 
Period 
Placebo  
Run-in  
Period 
Treatment  
Period 
Safety Follow-up 
Period 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
EOT/ETa 
8 
Telephone call 
Week 
−6 
−2 
 
2 
4 
8 
12 
14 
Day 
−42 to −15  
−14  
1 (Baseline) 
15 
29 
57 
85 
99 
Visit Window (Days) 
 
 
+3 
±3 
±3 
±3 
±3 
±3 
Randomization 
 
X 
X 
 
 
 
 
 
Dispense IMPn, o 
 
X 
X 
X 
X 
X 
 
 
Return IMP 
 
 
Xr 
X 
X 
X 
X 
 
IMP Adherence System and Compliance Checks 
 
X 
X 
X 
X 
X 
X 
 
AEs 
 
X 
X 
X 
X 
X 
X 
X 
Previous and concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BACS = Brief Assessment of Cognition for Schizophrenia; BAS-MPsQ = Basic Personal Traits Module of Multidimensional Psychological Questionnaire; 
CDSS = Calgary Depression Scale for Schizophrenia; CGI-S = Clinical Global Impression-Severity; CGI-I = Clinical Global Impression-Improvement; 
C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = 12-lead electrocardiogram; EOT = end of treatment; ESRS= Extrapyramidal Symptom Rating Scale; 
ET = early termination; EXP-MPsQ = Expectation Module of Multidimensional Psychological Questionnaire; MINI = Mini-International Neuropsychiatric Interview; 
PER-MPsQ = Perception Module of Multidimensional Psychological Questionnaire; PGIC = Patient Global Impression of Change; PK = pharmacokinetics; 
PANSS =  Positive and Negative Symptoms Scale; SQLS = Schizophrenia Quality of Life Scale; WOCBP = Women of childbearing potential. 
a. 
If a participant discontinues IMP prematurely (i.e., after Visit 3 but before the end of the treatment period) they are required to complete an EOT visit and 
complete the safety follow-up visit 2 weeks after their last dose. Participants who discontinue IMP prematurely should be encouraged to attend any outstanding 
trial visits. An ET visit should only be completed if the participant prematurely discontinues IMP and withdraws from the trial without continuing trial visits as 
per the trial schema. 
b. Video to be watched prior to administration of PANSS. 
c. 
Age of first use, duration since first regular use (years), current use within the last month, regular use once per week or more, and most common route of current 
administration (smoked, vaped, oral) will be recorded at screening. Number of days used in last 7 days and average grams used per day will be collected weekly 
via ePRO from Visit 2 using the IMP adherence monitoring Platform. 
d. A full physical examination at screening and a symptom-directed physical examination at Visit 3 and Visit 7. 
e. 
Height will be collected at screening only. 
f. 
To be collected prior to clinical laboratory assessments and PK sampling. 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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Page 102 of 104 
Clinical Protocol Template (Phase 2–4) 
V1, 24Sep15 
Clinical Protocol Global V2 Based on Clinical Protocol V1 11Nov2019 
g. Vital signs will include systolic/diastolic blood pressure, heart rate, respiratory rate, and temperature. Blood pressure should be taken after the participant has 
been in a supine position in a rested and calm state for at least 5 minutes. Blood pressure must be recorded using the same arm throughout the trial, where 
possible. 
h. An ECG will be performed after 5 minutes in a supine position, if possible. The ECGs should be done in triplicate at screening and baseline to ensure that QTcF 
< 450 msec (males)/ < 470 msec (females). Any subsequent ECG should be done once and should be repeated 2 times in cases where withdrawal criteria are met 
(QTcF ≥ 500 msec). 
i. 
To include HIV, hepatitis B, and hepatitis C. 
j. 
Plasma concentrations of the background antipsychotic medications will be assessed at Visit 1 and predose relative to the administration of IMP at Visit 4 and 
Visit 7.   
CBD and its major circulating metabolites will be assessed at Visit 1 and relative to the administration of IMP at Visits 4 and 7. A PK sample will be collected 
before the participant’s morning dose of IMP and within 12 hours (−3/+6 hours) since last IMP dose (Visit 4 and Visit 7). Following collection, the IMP will be 
administered with a meal of at least 300 kcal to be provided. At Visit 1, only a baseline PK sample will be collected. At Visit 4 and Visit 7, samples to determine 
concentrations of CBD and its major circulating metabolites will be collected pre- and postdose, relative to IMP, at a timepoint between 2 to 3 hours. Thereafter 
optional PK sampling may be collected at postdose time points between 4 to 6 hours and 8 to 10 hours. 
k. A drug screen test (urine) will include alcohol, amphetamines (including ecstasy), barbiturates, benzodiazepines, cocaine, methadone, opiates, and THC. THC 
will be blinded from Visit 3 to the end of the trial. 
l. 
Assessment to be conducted prior to dosing of any regular medication prescribed for the management of extrapyramidal side effects (e.g., anticholinergics, 
beta-blockers etc.). 
m. Every effort should be made to include informant information in the PANSS assessment through administration of the Informant Questionnaire PANSS. If 
contact with a participant’s informant cannot be made within 3-day window from the date of the study visit, either by phone or in person, then the informant 
interview should not be considered a barrier to visit progression. 
n. IMP is to be taken orally b.i.d., (e.g., morning and evening) preferably within 30 minutes of a meal using the syringe(s) provided. Participants will be asked to return 
all IMP (used and unused) at each relevant visit. The first dose of IMP at Visit 2 should be taken at the site. 
o. In cases where participants are not able to attend trial visits due special circumstances (e.g., COVID-19 pandemic), the investigator will discuss with the sponsor 
potential mitigation approaches for IMP dispensing, secure delivery, and collection. 
p. Eligibility review forms will be submitted for CST review once the diagnostic process and screening assessments are completed. 
q. If the participant discontinues IMP prematurely, PK assessment will not be collected. 
r. 
Participant must return placebo IMP prior to treatment period randomization. 
s. 
At Visit 2, the IMP Adherence smartphone application will be demonstrated to the participant. The first dose of IMP will be taken at site to demonstrate the use 
of the technology correctly. At following visits, IMP compliance will be checked through measuring the contents of the returned bottles. A participant who 
consistently fails to dose using the smartphone application should be followed up appropriately and re-trained by the site. 
.


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
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Page 103 of 104 
Clinical Protocol Template (Phase 2–4) 
V1, 24Sep15 
Clinical Protocol Global V2 Based on Clinical Protocol V1 11Nov2019 
 APPENDIX 2 
TRIAL PERSONNEL 
Appendix 2.1 
Investigator Details 
At the time of protocol production, the participating investigators have not been 
confirmed. A list of all investigators will be maintained within the GW master files 
(electronically and added to the trial master file at the end of the trial). 
Appendix 2.2 
Sponsor Contact Details 
Pharmacovigilance Department — SAE 
Reporting: 
Fax: +44 (0)1223 233 319 
(UK) 
USA Toll-free Fax: 
+1-866-234-1751 
Tel: +44 (0)1223 233 410 
Email: pvd@gwpharm.com 
Sponsor: 
GW Research Ltd 
Sovereign House 
Vision Park 
Chivers Way 
Histon 
Cambridge CB24 9BZ 
United Kingdom 
Tel: +44 (0) 1223 266 800 
Fax: +44 (0) 1223 235 667 
At the time of protocol production, the CROs, and the clinical and bioanalytical 
laboratories for the trial had not been confirmed. A corresponding list will be 
maintained within the GW master files (electronically and added to the trial master 
file at the end of the trial): 
Medical Advisor, 24-hour Emergency Contact 
Number, and Clinical Project Manager: 
Please refer to the Sponsor and 
Related Contact Details form 
in the trial site file. 
Clinical Trial Supplies: 
G-Pharm Ltd 
Tel: +44 (0) 1795 435 029 
Fax: +44 (0) 1795 475 439 
Trial Conduct 
Syneos Health 
1030 Sync Street 
Morrisville 
NC 27560 
United States 
 


SPONSOR: GW RESEARCH LIMITED 
Study Code: GWAP19030 
EudraCT Number: 2019-003369-16 
Clinical Protocol Global V3, 23Mar2021 
 
Confidential 
Page 104 of 104 
Clinical Protocol Template (Phase 2–4) 
V1, 24Sep15 
Clinical Protocol Global V2 Based on Clinical Protocol V1 11Nov2019 
Appendix 2.3 
Contract Research Organizations 
Syneos Health will monitor the trial. 
Syneos Health 
1030 Sync Street 
Morrisville 
NC 27560 
United States 
 

SAP_001.pdf: 
Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 1 of 36 
  
 
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GW Research Ltd. 
Study Code: GWAP19030 
 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-GROUP TRIAL TO 
INVESTIGATE THE SAFETY AND EFFICACY OF GWP42003-P 
VERSUS PLACEBO AS ADJUNCTIVE THERAPY IN PARTICIPANTS 
WITH SCHIZOPHRENIA EXPERIENCING INADEQUATE RESPONSE 
TO ONGOING ANTIPSYCHOTIC TREATMENT 
Statistical Analysis Plan 
 
08 April 2022 
 
 
 
 
 
P
I


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 2 of 36 
  
 
Confidential 
 
 
Approved by: 
 
 
 
Signatory 
Signature/date 
 Study Statistician 
GW Pharmaceuticals 
 
 
 
 
, Associate Director 
Biostatistics 
GW Pharmaceuticals 
 
 
 
 Clinical Science Lead 
GW Pharmaceuticals 
 
 
 
 
 
PI
PI
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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Page 3 of 36 
  
 
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CONTENTS 
1. 
INTRODUCTION 
7 
1.1 
Rationale 
7 
2. 
STUDY OBJECTIVES 
7 
2.1 
Efficacy 
7 
2.2 
Safety 
7 
2.3 
Exploratory 
7 
3. 
INVESTIGATIONAL PLAN 
8 
3.1 
Study Design 
8 
3.2 
Planned Sample Size 
8 
3.3 
Efficacy, Safety and Exploratory Endpoints 
9 
3.3.1 Efficacy Endpoints 
9 
3.3.2 Safety Endpoints 
9 
3.3.3 Exploratory Endpoints 
9 
4. 
BLINDED DATA REVIEW MEETING 
10 
5. 
STATISTICAL METHODS 
10 
5.1 
General Considerations 
10 
5.1.1 Missing Data 
11 
5.1.2 Day Numbering 
12 
5.1.3 Definitions 
12 
5.1.4 Covariates 
13 
5.2 
Analysis Sets and Protocol Deviations 
13 
5.2.1 Full Analysis Set 
13 
5.2.2 Safety Analysis Set 
13 
5.3 
Listings 
13 
5.4 
Demographic Data and Participant Characteristics 
13 
5.4.1 Participant Disposition 
13 
5.4.2 Analysis Sets 
14 
5.4.3 Demographic Data and Baseline Characteristics 
14 
5.4.4 Psychiatric History 
14 
5.4.5 Medical History 
15 
5.5 
Efficacy Analysis 
15 
5.5.1 General Approach 
15 
5.5.2 Efficacy Endpoints 
15 
5.6 
Exploratory Endpoints 
18 
5.7 
Safety Evaluation 
19 
5.7.1 Exposure and Compliance 
19 
5.7.2 Adverse Events 
20 
5.7.3 Clinical Laboratory Evaluation 
22 
5.7.4 Vital Signs, Other Physical Findings and Other Safety Data 
23 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
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5.8 
Other Measures 
25 
5.8.1 Concomitant Medication 
25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. 
REFERENCES 
27 
7. 
AMENDMENTS 
28 
8. 
ATTACHMENTS AND APPENDICES 
28 
APPENDIX 1 RANGES FOR CLINICALLY SIGNIFICANT CHANGES AND OTHER 
DEFINED FLAGGED VALUES IN VITAL SIGNS 
28 
APPENDIX 2 
DEFINED FLAGGED VALUES IN ECG PARAMETERS 
29 
APPENDIX 3 
TOXICITY CRITERIA FOR LABORATORY PARAMETERS 
30 
APPENDIX 4 
LIST OF TABLES, LISTINGS AND FIGURES 
32 
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
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ABBREVIATION 
ADR 
- 
Adverse drug reaction 
AE 
- 
Adverse event 
ALQ 
- 
Above limit of quantification 
ALT 
- 
Alanine aminotransferase 
ANCOVA 
- 
Analysis of covariance 
AST 
- 
Aspartate aminotransferase 
ATC 
- 
Anatomical therapeutic chemical 
BACS 
- 
Brief Assessment of Cognition for Schizophrenia 
BDRM 
- 
Blinded data review meeting 
b.i.d. 
- 
Twice daily 
BLQ 
- 
Below limit of quantification 
BMI 
- 
Body mass index 
BP 
- 
Blood pressure 
BSA 
- 
Body surface area 
 
 
 
CGI-I 
- 
Clinical Global Impression of Improvement 
CGI-S 
- 
Clinical Global Impression of Severity 
CI 
- 
Confidence interval 
CrCl 
- 
Creatinine Clearance 
CRF 
- 
Case report form 
C-SSRS 
- 
Columbia-Suicide Severity Rating Scale 
ECG 
- 
12-lead electrocardiogram 
 
 
 
Exp-MPsQ 
- 
Expectation-Multidimensional Psychological Questionnaire 
FAS 
- 
Full analysis set 
GW 
- 
GW Research Ltd 
IMP 
- 
Investigational medicinal product 
INR 
- 
International normalized ratio 
ITT 
- 
Intention to treat 
LOCF 
- 
Last observation carried forward 
LS 
- 
Least squares 
MedDRA 
- 
Medical Dictionary for Regulatory Activities 
MMRM 
- 
Mixed-effects model repeated measures 
 
 
 
PI
PI
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
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PANSS-G 
- 
Positive and Negative Symptom Scale-General 
PANSS-N 
- 
Positive and Negative Symptom Scale-Negative 
PANSS-P 
- 
Positive and Negative Symptom Scale-Positive 
PANSS-T 
- 
Positive and Negative Symptom Scale total 
 
 
 
PK 
- 
Pharmacokinetics 
 
 
 
QTc 
- 
QT interval corrected for heart rate 
SAP 
- 
Statistical analysis plan 
SAS 
- 
Statistical analysis software 
SCI-PANSS 
- 
Structured Clinical Interview Positive and Negative 
Symptoms Scale 
SOC 
- 
System organ class 
 
 
 
TEAE 
- 
Treatment-emergent adverse event 
ULN 
- 
Upper limit of normal 
US 
- 
United States 
PI
PI
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
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1. 
INTRODUCTION 
This statistical analysis plan (SAP) documents the statistical reporting to be performed for 
Study GWAP19030.   
This SAP has been prepared based on the following study documents:   
• 
Clinical Protocol Global (Version 3, dated 23 Mar 2021). 
• 
Case Report Form (CRF) GWAP19030, (Version 4.0, dated 29 June 2021). 
1.1 
Rationale 
Schizophrenia, a complex neurodevelopmental syndrome, results from gradual alterations 
in brain connectivity which may begin in utero, and symptoms (distorted thinking that affects 
language, perception, and sense of self) present and can persist for years before psychosis 
emerges.  
Symptoms are categorized into positive (e.g., hallucinations, delusions, and speech 
disturbance), negative (e.g., social withdrawal, apathy, and loss of emotional response), 
and cognitive domains. 
Antipsychotic medications, effective in the treatment of psychosis in most cases, act via 
antagonism of central dopamine receptor D2 however, numerous longitudinal studies have 
consistently noted significant heterogeneity and a high frequency of unfavorable outcomes 
in schizophrenia. Relapse rates reach 80% to 85% during the first 5 years of illness with 
three quarters of individuals discontinuing antipsychotic treatment in 18 months. A chronic 
course characterized by residual symptoms and/or relapses occurs in 34% to 57% of 
individuals. Treatment response is a key determinant of subsequent outcome, as it is an 
essential precondition for remission and recovery. Sub-optimally controlled psychotic 
symptoms are associated with a significant reduction in quality of life and functioning. There 
is therefore a substantial unmet need for new and effective therapies to treat schizophrenia. 
In this study the active Investigational Medicinal Product (IMP) is GWP42003-P oral 
solution. 
2. 
STUDY OBJECTIVES 
2.1 
Efficacy 
• 
To evaluate the efficacy of GWP42003-P versus placebo after 12 weeks of treatment. 
2.2 
Safety 
• 
To evaluate the safety and tolerability of GWP42003-P. 
 
 
 
 
 
 
 
 
PI
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
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3. 
INVESTIGATIONAL PLAN 
3.1 
Study Design 
This is a randomized, double-blind, placebo-controlled, parallel-group, outpatient trial. The 
trial will compare the efficacy and safety of 2 dose levels of GWP42003-P (150 mg twice 
daily [b.i.d.] and 500 mg b.i.d.) versus placebo in participants with schizophrenia who are 
experiencing an inadequate response to ongoing antipsychotic treatment. 
The duration of the trial will be approximately 20 weeks, which includes a screening period 
(up to 4 weeks), a single-blind placebo run-in period (2 weeks), a double-blind treatment 
period (12 weeks), and a safety follow-up period (2 weeks).  
After signing the informed consent form (ICF), participants will enter the screening period 
(Visit 1). The investigator will submit participants’ eligibility forms for clinical surveillance and 
training (CST) review. The CST will evaluate the eligibility of participants and provide the 
outcome of the evaluation to the site. Participants cannot be enrolled until site personnel 
have received the final CST notification. Additional details for CST will be described in the 
study manual. At Visit 2 screened participants who continue to meet eligibility criteria will be 
randomized 1:1 to receive 150 mg b.i.d. or 500 mg b.i.d. dose matched volumes of placebo 
in a single-blind manner for the placebo run-in period. At Visit 3 (Day 1) participants who 
continue to meet eligibility criteria will be randomized 2:1 to receive GWP42003-P or 
placebo of equivalent volume to their placebo run-in allocation in a double-blind manner for 
the treatment period.  
Randomization will be stratified by region (North America, Europe) and by sex (male, 
female).  
A safety follow-up visit will be conducted 2 weeks after the last dose of investigational 
medicinal product (IMP). If a participant discontinues IMP prematurely (i.e., before the end 
of the treatment period) they are required to attend an end of treatment (EOT) visit (±3 
days) and complete the safety follow-up visit 2 weeks after their last dose. Participants are 
encouraged to attend any outstanding visits per the trial schema. If a participant 
prematurely discontinues IMP and withdraws from the trial without continuing trial visits as 
per the trial schema, they are required to attend an early termination (ET) visit upon 
withdrawal and complete the safety follow-up visit 2 weeks after their last dose.  
Approximately 55 sites are expected to participate in this trial. The number of sites may be 
reduced or increased depending on recruitment performance. 
The study will aim to determine the efficacy, safety and tolerability of 2 dose levels of 
GWP42003-P compared with placebo. 
3.2 
Planned Sample Size 
Approximately 366 participants were to be randomized following the placebo run-in period 
to receive 1 of 2 dose levels of GWP42003-P (150 mg b.i.d. or 500 mg b.i.d.) or dose 
matching volume of placebo (150 mg b.i.d. and 500 mg b.i.d.) on a 2:2:1:1 basis. The 
placebo groups will be pooled for the analyses of efficacy.  
Assuming a common standard deviation of 11.0 and using a 2-sided hypothesis test at a 
0.05 α-level, a total sample size of 366 participants (122 participants per active dose group 
and 61 participants per placebo group) will provide 80% power to detect a significant result 
assuming a true treatment difference of −4.32 points on the PANSS-T score in change from 
baseline to end of treatment between 500 mg b.i.d., of GWP42003-P and placebo. This 
allows for a 15% drop-out rate, with a minimum of 309 participants needed to complete the 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
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trial. Depending on the drop-out rate during the trial, this number may be increased to 
ensure a minimum of 309 evaluable participants at Week 12.  
At least 366 participants were to be randomized to receive dose matching volume of 
placebo during the placebo run-in period (150 mg b.i.d. and 500 mg b.i.d. in a 1:1 ratio), 
thereafter randomized to receive GWP42003-P (150 mg b.i.d. or 500 mg b.i.d.) or dose 
matching volumes of placebo at a 2:1 ratio within each dose level. 
However, due to early termination of the study only 80 (22%) subjects were randomized. 
 
3.3 
Efficacy, Safety and Exploratory Endpoints 
3.3.1 
Efficacy Endpoints 
The efficacy of GWP42003-P versus placebo after 12 weeks of treatment is jointly 
measured by the following efficacy endpoints which will be compared between treatment 
groups: 
• 
Mean change from baseline to Week 12 in the following:  
o Structured Clinical Interview Positive and Negative Symptoms Scale (SCI-
PANSS) total (PANSS-T) score (30-210) 
o PANSS positive subscale (PANSS-P) score (7-49) 
o PANSS negative subscale (PANSS-N) score (7-49) 
o PANSS general subscale (PANSS-G) score (16-112) 
o Clinical Global Impression of Severity (CGI-S) score 
• 
Score at Week 12 in the Clinical Global Impression of Improvement (CGI-I) 
3.3.2 
Safety Endpoints 
The safety profile of GWP42003-P compared with placebo will be assessed at each dose 
level by measuring: 
• 
Changes in body weight, body mass index (BMI), and waist circumference 
• 
Changes in vital sign measurements 
• 
Adverse events (AEs) and adverse drug reactions (ADRs) 
 
 
 
• 
Clinical laboratory test results 
• 
12-lead electrocardiogram (ECG) parameters 
 
 
• 
Suicidality as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) 
 
 
 
 
PI
PI
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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4. 
BLINDED DATA REVIEW MEETING 
Prior to breaking the blind, it is anticipated that at least 1 Blinded Data Review Meeting 
(BDRM) will take place. The objectives of the meeting will include the identification and 
agreement on major and critical protocol deviations.  
The minutes of the BDRM will be documented separately. 
 
5. 
STATISTICAL METHODS 
5.1 
General Considerations 
In all tables, listings and figures, the treatment arms will be referred to and labelled as per 
Table 1. 
Table 1 
Study Treatments 
 
 
 
 
 
For safety tables where placebo is split by dose, an additional Pooled Placebo column will 
be included. 
In all tables, listings and figures, the study visits will be referred to and labelled as per 
Table 2. 
Endpoint 
Actual Treatment 
Treatment Label 
Efficacy and 
Exploratory 
Pooled Placebo 
Placebo 
Safety 
150 mg b.i.d Placebo 
Placebo 300 mg 
500 mg b.i.d Placebo 
Placebo 1000 mg 
Pooled Placebo 
Pooled Placebo 
All 
150 mg b.i.d GWP42003-P 
300 mg 
All 
500 mg b.i.d GWP42003-P 
1000 mg 
PI
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
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Table 2 
Study Visits 
Actual Visit 
Visit Label 
Visit 1: Screening 
Screening 
Visit 2: Placebo Run-in  
Day -14 
Visit 3: Day 1, baseline visit 
Day 1 
Visit 4: Day 15 
Day 15 
Visit 5: Day 29 
Day 29 
Visit 6: Day 57 
Day 57 
Visit 7 / Early Termination / End of 
Treatment*: Day 85 
Day 85 
Visit 8 Telephone call: Day 99 
Safety Follow-Up  
*If a participant discontinues IMP prematurely (i.e., after Visit 3 but before Visit 7) they are required to attend an 
End of Treatment visit and complete the safety follow-up visit 2 weeks after their last dose. The End of 
Treatment visit will be assigned to the nearest post-baseline visit (for which the assessment is scheduled to be 
performed), based on the trial day of the visit.  
 
Unless stated otherwise, continuous variables will be summarized showing the number of 
non-missing values (n), mean, standard deviation, median, minimum and maximum and 
categorical variables will be summarized showing the number and percentage of 
participants falling into each category. 
Minimum and maximum values will be presented to the same decimal precision as the raw 
data.  Mean and median will be presented to 1 more decimal place than the raw data, and 
standard deviation to 2 more decimal places than the raw data.  Percentages will be 
presented to 1 decimal place. 
All analyses and summaries will be produced using SAS Version 9.4 or higher. 
5.1.1 
Missing Data 
Every effort has been made to minimize missing data for this trial. All questionnaires will be 
completed on electronic devices. These assessments have been set up in such a way that 
the participant cannot proceed to the next question if they have not entered a response for 
the current question. The Cannabis Use Survey is the only exception, where a response to 
all questions is not required. 
 
 
5.1.1.1 Handling of Missing Data for the Efficacy Endpoints 
Efficacy endpoints will be based on all participants included in the analysis set using all 
available longitudinal data, either complete or partial. If a participant prematurely 
discontinues IMP during the treatment period but continues in the study, the data collected 
after their discontinuation of IMP will be used in the analysis of the efficacy endpoints.  
For CGI-S and CGI-I, the score 0 (= not assessed) will be set to missing.  
 
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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5.1.1.2 Adverse Events 
Missing and/or incomplete dates/times for AEs will be imputed in a manner resulting in the 
earliest onset or the longest duration during the treatment period, taking into account that 
the start date/time should not be after the stop date/time i.e. missing start dates will be 
imputed as the first day of the month/first month of the year and missing stop dates will be 
imputed as the last day of the month/last day of the year, while ensuring that the start 
date/time is not after the stop date/time. Stop dates/times will not be imputed if the AE is 
ongoing. 
The imputation method will only be used to determine treatment emergence, and imputed 
dates/times will not be presented in AE outputs. 
A worst-case approach will be followed in the event of missing severity or causality data.  If 
the severity is missing, ‘Severe’ will be imputed.  If causality data is missing, ‘Yes’ will be 
imputed for the question ‘Related to Study Drug?’. 
 
5.1.1.3 Concomitant Medication 
Missing concomitant medication dates will be handled in a similar fashion as described 
for AEs in Section 5.1.1.2. 
5.1.2 
Day Numbering 
The first day of treatment in the treatment period (Day 1) will be taken from ‘Date of first 
dose of IMP in Treatment Period’ on the Randomization CRF.  
Any days prior to Day 1 will be numbered relative to this day and calculated as: 
 
Date − (Date of Day 1) 
to give Day −1, −2, −3 etc. 
Any days post Day 1 will be calculated as:  
Date - (Date of Day 1) + 1 
5.1.3 
Definitions 
5.1.3.1 Baseline 
For clinic visit-based endpoints, baseline is defined as the last non-missing record or 
measure collected prior to the first dose of IMP in the treatment period.  
 
5.1.3.2 Last Visit 
Last visit for LOCF based analyses of efficacy endpoints assessed at clinic visits is defined 
as the last scheduled visit (not including the safety follow-up visit) at which a participant’s 
last evaluation is performed. 
 
5.1.3.3 Placebo Run-in Period 
The placebo run-in period is defined as Day -14 to Day -1 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
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5.1.3.4 Treatment Period 
The treatment period is defined as Day 1 to Day 85 
5.1.4 
Covariates 
Region strata will be defined as follows:  
• 
North America: Participants who participate in the United States of America will be 
pooled together; 
• 
Europe: All participants who participate in European countries (Poland, Serbia and 
Spain) will be pooled together. 
Sex strata will be defined as Stratum 1: Male; Stratum 2: Female.  
These covariates will be applied to the efficacy analyses and a number of exploratory 
analyses as outlined in Sections 5.5.2 and 5.6 respectively. 
5.2 
Analysis Sets and Protocol Deviations 
5.2.1 
Full Analysis Set 
All participants who were randomized at Visit 3 and received at least 1 dose of IMP in the 
treatment period will be included and analyzed according to their randomized treatment 
arm. This analysis set will be the primary analysis set for all efficacy endpoints. 
5.2.2 
Safety Analysis Set 
All participants who received at least one dose of IMP in the treatment period will be 
included and analyzed according to the treatment received.  Only participants for whom it 
has been confirmed that they did not take any IMP in the treatment period will be excluded 
from this safety analysis set. This analysis set will be used to report the safety data. 
5.3 
Listings 
All data will be listed and ordered by site, treatment, participant number and, where 
appropriate, chronological order of assessment.  Listings will be created for each of the 
subsequent sections of the SAP.  
Visit date need not be included on all of the listings, but day numbers will be included, 
where appropriate.  
Other derived variables (e.g. changes from baseline values) that are calculated for analysis 
purposes or to aid interpretation of the data will be added to the listings as appropriate. 
5.4 
Demographic Data and Participant Characteristics 
5.4.1 
Participant Disposition 
Participant disposition will be summarized using standard summary statistics for all 
screened participants.  The number screened, number of screen failures, reasons for 
failures, number randomized to the placebo run-in period, number of placebo run-in failures, 
reasons for failure and number randomized to the treatment period, withdrawals and 
reasons for withdrawals will be included.  


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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5.4.2 
Analysis Sets 
Participants included in the safety and full analysis sets and participants excluded together 
with reasons for exclusion will be summarized by absolute counts (n) and percentages (%). 
5.4.3 
Demographic Data and Baseline Characteristics 
The following demographic data will be summarized by treatment group and overall for the 
full analysis sets: 
• 
Age (years); 
• 
Sex; 
• 
Race; 
• 
Ethnic origin 
• 
Country; 
• 
Region (United States, Europe); 
• 
Weight at baseline (kg); 
• 
Height at baseline (cm); 
• 
Waist circumference (cm); 
• 
Body mass index at baseline (kg/m2). 
Age will be calculated as: 
(Date of screening – date of birth+1) ÷ 365.25. 
The following baseline cannabis use data taken from the ‘Cannabis Use Survey’ CRF page 
will be summarized by treatment group and overall for the safety analysis sets: 
• 
Age of first use (years). 
• 
Duration since first regular use (years). 
• 
Currently using cannabis (yes/no). 
• 
Regularly using cannabis (yes/no). 
• 
Most common route of current use (smoked, vaped, oral). 
5.4.4 
Psychiatric History 
The following psychiatric history data will be listed only: 
• 
Date of first diagnosis of schizophrenia. 
• 
Date of most recent relapse or acute exacerbation of schizophrenia. 
All recorded comorbid psychiatric disorder history will be coded using Version 24.1 of the 
Medical Dictionary for Regulatory Activities (MedDRA). 
The number of participants with comorbid psychiatric disorder history by system organ 
class, and preferred term, will be summarized by absolute counts (n) and percentages (%) 
for the safety analysis sets.  Percentages will be calculated based on the number of 
participants in the specific treatment arm. Two tables will be produced, one including any 
events classified as resolved at screening, and the other including all current conditions.  


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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5.4.5 
Medical History  
All recorded relevant or significant medical history or current conditions reported other than 
psychiatric disorders on the ‘medical history’ CRF page will be coded and summarized 
using the same method outlined in Section 5.4.4. 
5.5 
Efficacy Analysis 
5.5.1 
General Approach 
The efficacy analyses will use the FAS. No formal hypothesis test will be performed due to 
early termination of the study (see Section 3.2). Instead, the point estimates and 95% CI for 
the effects will be presented for efficacy parameters of interest.  However, p-values will be 
presented for flagging purposes and not to be used for results interpretation. 
5.5.2 
Efficacy Endpoints 
The efficacy of GWP42003-P versus placebo after 12 weeks of treatment is measured by 
the following efficacy endpoints which will be compared between treatment groups: 
• 
Mean change from baseline to Week 12 in the following:  
o Structured Clinical Interview Positive and Negative Symptoms Scale (SCI-
PANSS) total (PANSS-T) score  
o PANSS positive subscale (PANSS-P) score  
o PANSS negative subscale (PANSS-N) score  
o PANSS general subscale (PANSS-G) score  
o Clinical Global Impression of Severity (CGI-S) score  
• 
Score at Week 12 in the Clinical Global Impression of Improvement (CGI-I) 
 
5.5.2.1 PANSS-T 
The SCI-PANSS is a medical scale used for measuring symptom severity of participants 
with schizophrenia or related psychotic disorder. The name refers to the 2 types of 
symptoms in schizophrenia, as defined by the American Psychiatric Association: positive 
symptoms, which refer to an excess or distortion of normal functions (e.g., hallucinations 
and delusions), and negative symptoms, which represent a diminution or loss of normal 
functions.  
It is a 30-item rating instrument that assesses the positive and negative symptoms of 
schizophrenia as well as symptoms of general psychopathology. Individual items are rated 
on a 7-point scale, where 1 = absent and 7 = extreme. A PANSS-T score is derived from 
the sum of the 30 items and the total score ranges from 30 to 210.  Missing data will be 
handled as specified in Section 5.1.1.1.  This scale will be measured at each assessment 
visit, with the primary time point of interest being Day 85.   
The change from baseline in PANSS-T score will be analyzed using a mixed-effects 
repeated measures (MMRM) model. An MMRM model will be fitted to the change in 
PANSS-T score at each visit and will include stratification factors (sex [male or female] and 
region [North America or Europe]), associated baseline, visit, treatment arm, visit by 
treatment arm interaction and visit by associated baseline interaction as fixed effects and 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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visit repeated within each participant as a repeated effect. For the analysis of the PANSS-T 
score; baseline PANSS-P, baseline PANSS-N and PANSS-G will be included in the model 
as fixed effects for the associated baseline instead of baseline PANSS-T. 
The PROC MIXED procedure in SAS will be utilized to perform the analysis.  An 
unstructured covariance matrix will be used to estimate the variance-covariance structure 
within participants across time points. If convergence is not obtained, or model fit is not 
adequate then other covariance structures will be explored in the following order until the 
model converges: 
• 
Toeplitz 
• 
First-order autoregressive 
• 
Compound Symmetry 
This order is specified according to a decreasing number of covariance parameters in the 
structure. The primary analysis will use the first covariance structure converging to the best 
fit. If a structured covariance is used, the sandwich estimator for the covariance estimation 
will be used by specifying the EMPIRICAL options in the PROC MIXED procedure in SAS 
with the aim to deal with model misspecification of the covariance matrix.  
The least squares (LS) mean estimates for each treatment arm at each visit, along with the 
standard error and 95% confidence intervals (CIs) will be presented.  In addition, the 
estimate of the treatment difference at each visit will be presented along with standard 
errors of the difference and associated 95% CIs. The primary comparison is the estimate of 
the difference at Day 85. 
For participants who complete the trial, regardless of whether IMP is prematurely 
discontinued or not, the visit effect used in the analysis will correspond to the associated 
score at each trial visit. However, participants who withdraw from the trial are required to 
complete the procedures for End of Treatment at the time of withdrawal. For these 
participants, their End of Treatment data will be assigned to the nearest post-baseline visit 
(for which the assessment is scheduled to be performed), based on the trial day of the visit.  
The values including change from baseline for PANSS-T will be summarized using standard 
summary statistics for the full analysis set.  
5.5.2.2 PANSS-P 
The PANSS ‘P’ Scale will be calculated as the sum of the items prefixed with an P, 7 items 
in total, i.e. delusions, conceptual disorganization, hallucinatory behavior, excitement, 
grandiosity, suspiciousness/persecution and hostility. The primary time point of interest will 
be Day 85. 
The change from baseline in PANSS-P score will be analyzed using the same MMRM 
approach as specified in Section 5.5.2.1. Baseline PANSS-P will be included in the model 
as a fixed effect for the associated baseline.  
The values including change from baseline for PANSS-P will be summarized using standard 
summary statistics for the full analysis set.  
5.5.2.3 PANSS-N 
The PANSS ‘N’ Scale will be calculated as the sum of the items prefixed with an N, 7 items 
in total, i.e. blunted affect, emotional withdrawal, poor rapport, passive/apathetic social 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
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withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and 
stereotyped thinking. The primary time point of interest will be Day 85.  
The change from baseline in PANSS-N score will be analyzed using the same MMRM 
approach as specified in Section 5.5.2.1. Baseline PANSS-N will be included in the model 
as a fixed effect for the associated baseline. 
The values including change from baseline for PANSS-N will be summarized using 
standard summary statistics for the full analysis set.  
5.5.2.4 PANSS-G 
The PANSS ‘G’ Scale will be calculated as the sum of the items prefixed with a G, 16 items 
in total, i.e. somatic concerns, anxiety, guilt feelings, tension, mannerisms and posturing, 
depression, motor retardation, uncooperativeness, unusual thought content, disorientation, 
poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, 
preoccupation and active social avoidance. The primary time point of interest will be Day 
85.   
The change from baseline in PANSS-G score will be analyzed using the same MMRM 
approach as specified in Section 5.5.2.1. Baseline PANSS-G will be included in the model 
as a fixed effect for the associated baseline. 
The values including change from baseline for PANSS-G will be summarized using 
standard summary statistics for the full analysis set. 
5.5.2.5 CGI-S 
The CGI-S is a 7-point scale used to rate the severity of participants’ illness at the time of 
assessment. Considering total clinical experience, a participant will be assessed on severity 
of mental illness at the time of rating 0 = not assessed; 1 = normal, not at all ill; 2 = 
borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = 
among the most extremely ill participants. The CGI-S will be assessed at Visits 1, 2, 3, 4, 5, 
6 and 7. 
The numeric values of CGI-S assessments will be analyzed separately using the same 
MMRM approach as specified in Section 5.5.2.1. Baseline CGI-S score will be included as a 
covariate. Both values for the original categorical scale and the converted numerical scale 
at each visit including change from baseline for the CGI-S numerical scale will be 
summarized using standard summary statistics for the full analysis set.  
5.5.2.6 CGI-I 
The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's 
illness has improved or worsened relative to a baseline state at the beginning of the 
intervention. This is rated as: 0 = not assessed; 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 CGI-I will be measured at Visits 4, 5, 6 and 7.  
The numeric values of CGI-I assessments will be analyzed separately using the same 
MMRM approach as specified in Section 5.5.2.1. Baseline CGI-S will be included as a 
covariate. Both values for the original categorical scale and the converted numerical scale 
at each visit will be summarized using standard summary statistics for the full analysis set. 
 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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5.7.2 
Adverse Events 
All reported AEs will be classified by system organ class (SOC), preferred term and lower 
level term using Version 24.1 of MedDRA. 
Summaries will be presented by treatment group as well as SOC and preferred term. 
A treatment period treatment emergent AE (TEAE) is defined as an AE with a start date on 
or after the first dose of IMP during the treatment period (Day 1), or an AE that was present 
prior to the first dose of IMP during the treatment period but has increased its intensity 
during the treatment period.  
If an AE has a partial start date and it is unclear from the partial date (or the stop date) 
whether the AE started prior to or post first dose of IMP then the AE will be considered 
treatment emergent and if it is unclear which period the event started, it will be assigned to 
both periods.   
An AE will be considered treatment-related if the plausibility relationship to IMP is recorded 
on the CRF as ‘yes’.  If the data on plausibility relationship to IMP is missing then the AE will 
be considered treatment-related. 
An AE will be considered leading to permanent discontinuation of IMP if the action taken 
with IMP is recorded on the CRF as ‘trial medication stopped’ or the outcome is recorded on 
the CRF as ‘patient died’. 
An AE will be considered leading to IMP dose reduction excluding permanent 
discontinuation if the action taken with IMP is recorded on the CRF as ‘dose reduced’, ‘dose 
reduced temporarily’ or ‘trial medication interrupted’. 
An AE will be considered leading to temporary IMP dose reduction if the action taken with 
IMP is recorded on the CRF as ‘dose reduced temporarily’. 
An AE will be considered leading to permanent IMP dose reduction excluding permanent 
discontinuation if the action taken with IMP is recorded on the CRF as ‘dose reduced’. 
An AE will be considered fatal if the outcome is recorded on the CRF as ‘patient died’. 
For the summary of TEAEs by maximal severity, for each participant, the worst severity 
recorded by preferred term, SOC and overall will be used for summary purposes.  If severity 
is missing, the worst case (severe) will be assumed. 
PI


Trial Code: GWAP19030 
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For summaries by resolution, AEs with an outcome of ‘recovered’ or ‘recovered with 
sequelae’ will be summarized as ‘Resolved’ and AEs with an outcome of ‘continuing’, 
‘patient died’ or those with a missing outcome will be summarized as ‘Not resolved’. 
For the summary of TEAEs by time of first onset of AE, data will be summarized for the 
treatment period separately under the following categories: 
• 
Weeks 1–2 (Day 1 to 14). 
• 
Weeks 3–4 (Day 15 to 28). 
• 
Weeks 5–8 (Day 29 to 56). 
• 
Weeks 9–12 (Day 57 to 84). 
• 
>12 weeks (> Day 84).  
The time to first onset of AE in treatment period will be calculated for TEAEs as: 
Start date of AE – Date of first dose of IMP in treatment period + 1 
If participants have multiple occurrences of an AE then the AE will be counted once for the 
first occurrence only.  Percentages will be based on the number of participants in the safety 
analysis set who have a visit or follow-up call within each time period above. 
For the summary of TEAEs by time to AE resolution, data will be summarized under the 
following categories: 
• 
1 week (≤7 days). 
• 
2 weeks (8–14 days). 
• 
3 weeks (15–21 days). 
• 
4 weeks (22–28 days). 
• 
>4 weeks (>28 days). 
• 
Ongoing (for AEs not resolved). 
The time to AE resolution will be calculated for TEAEs as: 
Stop date of AE – Start date of AE + 1 
If participants have multiple occurrences of an AE then the AE will be counted once for the 
occurrence with the longest time to AE resolution.  However, if any of the AEs are not 
resolved then the AE will be counted once within the ‘Ongoing’ category. 
The start and stop day of the AE relative to the first dose of IMP will be calculated as per 
Section 5.1.2.  For partial dates, if it is clear from the partial date that the start/stop day was 
prior to the first dose of IMP, then ‘pre’ will be listed, similarly if it is clear that the event was 
post the first dose of IMP then ‘post’ will be listed as the start/stop day as appropriate. 
Listings will include the start and stop day of the AE, a flag for treatment emergence, and 
limited demographic information about the participant (age, sex, race and weight at 
screening).   
 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
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5.7.3 
Clinical Laboratory Evaluation 
5.7.3.1 Hematology and Chemistry 
Hematology and chemistry safety parameters are measured at Visits 1, 3, 5 and 7. 
Summaries will be presented by treatment group for each laboratory parameter at each visit 
for the safety analysis set. Change from baseline and percent change from baseline to each 
post-baseline visit will also be presented. 
If values for any of the parameters are below or above the limit of quantification of the assay 
(BLQ or ALQ), then they will be included in the summary tables at the BLQ or ALQ 
thresholds.  However, for estimated creatinine clearance, results >60 are reported only as 
‘>60’.  Hence, estimated creatinine clearance (CrCl) will be calculated using the Cockcroft-
Gault equation: 
CrCl (mL/min) = [(140 - age) × weight × k] / serum creatinine 
where age is measured in years, weight is measured in kg, k = 1.23 if male, k = 1.04 if 
female and serum creatinine is measured in µmol/L.  
CrCl will be indexed to body surface area (BSA) using the following formula: 
Corrected CrCl (mL/min/1.73m2) = CrCl (mL/min) × 1.73/BSA 
where BSA is based on the Du Bois and Du Bois formula: 
weight 0.425 × height 0.725 × 0.007184 
where weight is measured in kg and height is measured in cm. 
When available, enzymatic serum creatinine will be used.  Otherwise, the Jaffe serum 
creatinine will be used.  If height or weight is missing at the collection date, then the closest 
value to the sample date will be used.  If there is more than one height or weight value on 
the same day or 2 height or weight values equally distant from the collection date, then the 
mean will be used.  
Where laboratory samples are repeated, the baseline value is defined as the final recorded 
value prior to the first dose of IMP.  
Shift tables for hematology and biochemistry parameters will be constructed, based upon 
normal ranges and GW toxicity limits (See Section 8), to determine the categorical shifts 
from baseline to each post-baseline visit in the treatment period.  Values will be categorized 
as ‘Normal’, ‘Low’ or ‘High’ based on normal ranges and ‘Toxically Low’, ‘Toxically Normal’ 
or ‘Toxically High’ based on GW toxicity limits. 
For CrCl, results will be assigned to the following grades: 
• 
Normal: >60 ml/min/1.73 m2 
• 
Grade 1: 60 ml/min/1.73 m2 
• 
Grade 2: ≥30 and <60 ml/min/1.73 m2 
• 
Grade 3: ≥15 and <30 ml/min/1.73 m2 
• 
Grade 4:  <15 ml/min/1.73 m2 
A separate shift table will be produced for CrCl based upon the above grades to determine 
the categorical shifts from baseline to each post-baseline visit. 
Table will be produced summarizing the number of participants meeting the following 
criteria:  


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 23 of 36 
  
 
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• 
Alanine aminotransferase (ALT) > 1×ULN at baseline 
• 
Aspartate aminotransferase (AST) > 1×ULN at baseline 
• 
AT > 1×ULN at baseline 
• 
Treatment emergent ALT > 3×ULN, > 5×ULN and > 8×ULN 
• 
Treatment emergent AST > 3×ULN, > 5×ULN and > 8×ULN 
• 
Treatment emergent AT > 3×ULN, > 5×ULN and > 8×ULN 
• 
Treatment emergent AT > 3×ULN and either bilirubin > 2×ULN or INR > 1.5  
where AT is AST or ALT, and treatment emergent is defined as criteria not met at baseline 
but met at any time post-baseline.  The above will be summarized overall and for sex (male, 
female). 
All laboratory data will be listed; listings will include limited demographic information about 
the participant (age, sex, race and weight at baseline).  Abnormal laboratory values will be 
listed separately.  A further listing will be created for the laboratory reference ranges and 
toxicity limits. A listing of liver parameters (ALT, AST, bilirubin and INR) will be produced 
that includes the baseline result, result at the particular visit, change from baseline, upper 
limit of normal (ULN) value, ratio of result to baseline and ratio of result to ULN. 
5.7.3.2 Serology 
Serology is assessed at Visit 1 and will be listed only. 
5.7.3.3 Urinalysis 
Urinalysis is assessed at Visits 1, 3, 4, 6 and 7 and will be listed only. 
5.7.3.4 Drug Screen 
A drug screen is performed at Visits 1, 3 and 7. Results will be summarized by treatment 
group for each parameter and visit for the safety analysis set.  
5.7.3.5 Pregnancy Test  
Pregnancy test results will be summarized by treatment group and visit for the safety 
analysis set.  
5.7.4 
Vital Signs, Other Physical Findings and Other Safety Data 
5.7.4.1 Vital Signs 
Summaries will be presented by treatment group for each vital sign parameter at each visit 
for the treatment period. Change from baseline to each post-baseline visit will also be 
presented for the treatment period. 
Based on the criteria presented in Section 8, clinically significant changes from baseline in 
vital signs measurements (except waist circumference) and other defined flagged values 
will be identified at each visit.  The number of participants with a clinically significant change 
from baseline will be summarized for the treatment period by parameter, visit and treatment 
group. The number of participants with at least one post-baseline flagged vital sign 
parameter value will be summarized by parameter, flagged criteria and treatment group. 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 24 of 36 
  
 
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5.7.4.2 Electrocardiogram 
An ECG will be performed at Visits 1, 3, and 7. Summaries will be presented for ventricular 
rate, PR interval, QRS duration, QT interval and QTcF by treatment group at each visit.  
Change from baseline to Day 85 will also be presented. 
Based on the criteria presented in Section 8, defined flagged values will be identified at 
each visit.  The number of participants with at least one post-baseline flagged ECG 
parameter value will be summarized for the treatment period by parameter, flagged criteria 
and treatment group.  
5.7.4.3 Physical Examination 
A physical examination will be performed at Visits 1, 3, and 7 and will be listed only. 
Any relevant findings at screening are included as part of the participant’s medical history.  
Any changes seen after screening that are indicative of an AE are to be recorded as such 
on the AE form and included as part of the AE summaries. 
Additionally, body weight, BMI, waist circumference, and height (collected at Visit 1 only) 
are recorded as part of the physical examination.  Body weight, BMI, waist circumference, 
and height will be summarized and listed together with the vital signs parameters. 
5.7.4.4 Columbia-Suicide Severity Rating Scale (Adult’s) 
The C-SSRS is completed at Visits 1, 2, 3, 4, 5, 6 and 7, for all participants.  Questions are 
asked on suicidal behavior, suicidal ideation and intensity of ideation.  At the screening visit, 
questions are in relation to lifetime experiences and all subsequent questioning in relation to 
the last assessment (since last visit). 
The following C-SSRS data will be summarized for the treatment period by treatment group 
at each visit for participants in the safety analysis sets: 
• 
Incidence of the following suicidal ideation: 
o Wish to be dead. 
o Non-specific active suicidal thoughts. 
o Active suicidal ideation with any methods (not plan) without intent to act. 
o Active suicidal ideation with some intent to act, without specific plan. 
o Active suicidal ideation with specific plan and intent. 
• 
Incidence of the following suicidal behavior: 
o Actual attempt. 
o Interrupted attempt. 
o Aborted attempt. 
o Preparatory acts or behavior. 
o Suicidal behavior. 
o Completed suicide.  
 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 25 of 36 
  
 
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5.8 
Other Measures 
5.8.1 
Concomitant Medication 
Medications will be coded using the World Health Organization Drug Dictionary, Version 
WHODrug-Global-B3\\202109. A medication will be considered concomitant for each period 
if it has a start date on or after the first dose of IMP for the corresponding period or if it was 
started prior to the first dose of IMP and was ongoing.  If a medication has a partial or 
missing start/stop date and it is unclear from the date whether the medication was taken 
after the first dose of IMP then it will be considered concomitant. 
For summaries and listings of medications the following approach will be used to determine 
the Anatomical Therapeutic Chemical (ATC) term to be presented: 
• 
If coded to level 4 then the level 4 coded term will be presented. 
• 
If coding is not performed at level 4 but level 3 coding is present then level 3 coded 
term will be presented. 
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 26 of 36 
  
 
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• 
If coding is not performed at level 3 but level 2 coding is present then the level 2 
coded term will be presented. 
• 
If coding is not performed at level 2 but level 1 coding is present then the level 1 
coded term will be presented. 
Summaries of each of the following by ATC term and preferred term will be summarized by 
absolute counts (n) and percentages (%) for treatment period (unless stated otherwise): 
• 
History of antipsychotic medications (placebo run-in period only); 
• 
Concomitant antipsychotic medications; and 
• 
Other concomitant medications. 
The ATC term, preferred term, reported generic name and reported brand name will be 
listed. 
The start day and stop day will be included in the listing according to Section 5.1.2.  If the 
date is partial and the exact day is unknown then the text ‘pre’ or ‘post’ will replace the start 
or stop day if it is clear from the partial date that the medication started or stopped prior to 
or after the first dose of IMP. 
 
 
 
 
 
 
 
 
 
  
 
  
 
  
 
  
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 27 of 36 
  
 
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PI


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 28 of 36 
  
 
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6. 
REFERENCES 
 
7. 
AMENDMENTS 
Notable changes to the SAP that were completed prior to unblinding, are given below.  
Minor changes, clarifications and corrections are not listed. 
Date 
Section 
Description of Change 
 
 
 
8. 
ATTACHMENTS AND APPENDICES 
Appendix 1 Ranges for Clinically Significant Changes and Other Defined Flagged 
Values in Vital Signs 
The range of values that will be used to identify clinically significant changes in vital signs 
parameters (See Section 5.7.4.1) are presented in Table 4. 
 
Table 4 
Ranges for Clinically Significant Changes in Vital Signs  
Vital Sign 
Range 
Sitting Systolic BP 
Change: < -20, > 20 
Sitting Diastolic BP 
Change: < -10, > 10 
Heart Rate 
Change: < -20, > 20 
Weight 
Percent Change: ≤ -7, ≥ 7 
 
Defined flagged values that will be used to identify low or high vital signs parameters (See 
Section 5.7.4.1) are presented in Table 5. 
 
Table 5 
Other Defined Flagged Values for Vital Signs 
Vital Sign 
Flag 
Sitting Systolic BP 
< 90, > 140, > 160 
Sitting Diastolic BP 
< 50, > 90, > 100 
Heart Rate 
< 60, > 100 
Temperature 
> 38, < 36 
Respiratory Rate 
< 12, > 20 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 29 of 36 
  
 
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Appendix 2 
Defined Flagged Values in ECG Parameters 
Defined flagged values that will be used to identify low or high ECG parameters (See 
Section 5.7.4.2) are presented in Table 6. 
 
Table 6 
Defined Flagged Values for ECG Parameters 
ECG Parameter 
Flag 
QTc  
> 450, > 480, > 500 
 
 
 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 30 of 36 
  
 
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Appendix 3 
Toxicity Criteria for Laboratory Parameters 
The toxicity criteria that will be used to identify abnormal laboratory parameters are 
presented in Table 7 and Table 8. 
Table 7 
Toxicity Criteria for Biochemistry Parameters 
Parameter 
Toxicity Decrease 
Toxicity Increase 
Chloride 
0.96xLL 
1.04xUL 
Calcium 
0.89xLL 
1.16xUL 
Sodium 
0.96xLL 
1.04xUL 
Potassium 
0.90xLL 
1.10xUL 
Glucose (mmol/L) 
3.2 
11 
Phosphate 
0.79xLL 
 
Cholesterol 
0.85xLL 
1.6xUL 
AST 
 
3xUL 
ALT 
 
3xUL 
Lactate Dehydrogenase 
 
2.6xUL 
Alkaline phosphatase 
 
2xUL 
Gamma GT 
 
3xUL 
Bilirubin 
 
>2xUL 
Albumin 
0.84xLL 
 
Total protein 
0.84xLL 
1.16xUL 
Urea 
 
2.6xUL 
Blood urea nitrogen 
 
2.6xUL 
Creatinine 
 
1.5xUL 
Uric acid 
 
1.16xUL 
         UL = upper limit of reference range 
 
LL = lower limit of reference range 
 
 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 31 of 36 
  
 
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Table 8 
Toxicity Criteria for Hematology Parameters 
Parameter 
Toxicity 
Decrease 
Toxicity Increase 
Hemoglobin (g/dL) 
9.4 
 
Hematocrit (%) 
28 
 
Red cell count 
0.84xLL 
 
Mean corpuscular volume 
0.84xLL 
1.11xUL 
Mean corpuscular hemoglobin 
0.84xLL 
 
Mean corpuscular hemoglobin 
concentration 
0.84xLL 
 
Platelets (x10^9/L) 
74 
 
Prothrombin time 
 
>1.5xUL 
Prothrombin international normalized ratio 
 
>1.5 
Total white blood cell count (x10^9/L) 
2.9 
21 
Total neutrophil count (x10^9/L) 
1.36 
14.7 
Segmented neutrophil count (x10^9/L) 
0.75 
12.3 
Eosinophils (x10^9/L) 
 
1.5 
Basophils (x10^9/L) 
 
0.31 
Monocytes (x10^9/L) 
 
2.1 
Lymphocytes (x10^9/L) for participants 
<18 years (auto hematology) 
1.0 
 
Lymphocytes (x10^9/L) for participants 
<18 years (manual hematology) 
0.2 
 
Lymphocytes (x10^9/L) for participants 
≥18 years 
£0.2 
 
               UL = upper limit of reference range  
LL = lower limit of reference range 
 
 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 32 of 36 
  
 
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Appendix 4 
List of Tables, Listings and Figures 
Lists of the tables, listings and figures to be provided are given below in Table 9, Table 10 
and Error! Reference source not found., respectively. 
Table 9 
List of Tables 
Table Number 
Title 
Analysis Set 
Table 14.1.1 
Summary of Participant Disposition 
All Screened subjects 
Table 14.1.2 
Summary of Demographic Data 
Full Analysis Set 
Table 14.1.3 
Summary of Baseline Characteristics 
Full Analysis Set 
Table 14.1.4 
Summary of Psychiatric History Now Resolved 
Safety Analysis Set 
Table 14.1.5 
Summary of Psychiatric History – Current Conditions  
Safety Analysis Set 
Table 14.1.6 
Summary of Previous Significant Non-Psychiatric 
History Now Resolved 
Safety Analysis Set 
Table 14.1.7 
Summary of Significant Non-Psychiatric History – 
Current Conditions 
Safety Analysis Set 
Table 14.1.8 
Summary of Concomitant Antipsychotic Medications 
Safety Analysis Set 
Table 14.1.9 
Summary of Other Concomitant Medications 
Safety Analysis Set 
Table 14.1.10 
Summary of Treatment Compliance 
Safety Analysis Set 
Table 14.2.1.1 
Summary of PANSS-T 
Full Analysis Set 
Table 14.2.1.2 
Analysis of Change from Baseline in PANSS-T During 
Treatment Period – MMRM 
Full Analysis Set 
Table 14.2.2.1 
Summary of PANSS-P 
Full Analysis Set 
Table 14.2.2.2 
Analysis of Change from Baseline in PANSS-P During 
Treatment Period – MMRM 
Full Analysis Set 
Table 14.2.3.1 
Summary of PANSS-N 
Full Analysis Set 
Table 14.2.3.2 
Analysis of Change from Baseline in PANSS-N During 
Treatment Period – MMRM 
Full Analysis Set 
Table 14.2.4.1 
Summary of PANSS-G 
Full Analysis Set 
Table 14.2.4.2 
Analysis of Change from Baseline in PANSS-G During 
Treatment Period – MMRM 
Full Analysis Set 
Table 14.2.5.1 
Summary of the Caregiver Global Impression of 
Severity 
Full Analysis Set 
Table 14.2.5.2 
Analysis of the Caregiver Global Impression of Severity 
Full Analysis Set 
Table 14.2.6.1 
Summary of the Caregiver Global Impression of 
Improvement 
Full Analysis Set 
Table 14.2.6.2 
Analysis of the Caregiver Global Impression of 
Improvement (MMRM) 
Full Analysis Set 
Table 14.2.7.1 
Summary of PANSS Marders Factors  
Full Analysis Set 
Table 14.2.7.2 
Analysis of Change from Baseline in PANSS Marders 
Factors During Treatment Period - MMRM 
Full Analysis Set 
Table 14.2.8 
Summary of BACS 
Full Analysis Set 
Table 14.2.9 
Analysis of the Response of Caregiver Global 
Impression of Improvement  
Full Analysis Set 
Table 14.3.1 
Summary of Exposure 
Safety Analysis Set 
Table 14.3.2.1 
Overall Summary of Treatment Emergent Adverse 
Events 
Safety Analysis Set 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 33 of 36 
  
 
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Table Number 
Title 
Analysis Set 
Table 14.3.2.2 
Summary of Treatment Emergent Adverse Events 
Safety Analysis Set 
Table 14.3.2.3 
Summary of Treatment-Related Treatment Emergent 
Adverse Events 
Safety Analysis Set 
Table 14.3.2.4 
Summary of Treatment Emergent Adverse Events by 
Maximal Severity 
Safety Analysis Set 
Table 14.3.2.5 
Summary of Treatment Emergent Adverse Events by 
Sex 
Safety Analysis Set 
Table 14.3.2.6 
Summary of TEAEs by Time of First Onset of AE 
Safety Analysis Set 
Table 14.3.2.7 
Summary of TEAEs by Time to AE Resolution 
Safety Analysis Set 
Table 14.3.2.8 
Summary of TEAEs Reported in >=2% of Participants in 
the GWP42003-P Treatment Groups 
Safety Analysis Set 
Table 14.3.2.9 
Summary of Non-Serious Treatment Emergent Adverse 
Events 
Safety Analysis Set 
Table 14.3.2.10 
Summary of Treatment Emergent Adverse Events by 
Event 
Safety Analysis Set 
Table 14.3.2.11 
Summary of Treatment-Related Treatment Emergent 
Adverse Events by Event 
Safety Analysis Set 
Table 14.3.2.12 
Summary of Non-Serious Treatment Emergent Adverse 
Events by Event 
Safety Analysis Set 
Table 14.3.3.1 
Summary of Fatal Treatment Emergent Adverse Events 
Safety Analysis Set 
Table 14.3.4.1 
Summary of Serious Treatment Emergent Adverse 
Events 
Safety Analysis Set 
Table 14.3.3.1 
Summary of Serious Treatment Emergent Adverse 
Events by Event 
Safety Analysis Set 
Table 14.3.4.2 
Summary of Treatment-Related Serious Treatment 
Emergent Adverse Events 
Safety Analysis Set 
Table 14.3.4.1 
Summary of Treatment-Related Serious Treatment 
Emergent Adverse Events by Event 
Safety Analysis Set 
Table 14.3.5.1 
Summary of Treatment Emergent Adverse Events 
Leading to Permanent Discontinuation of IMP 
Safety Analysis Set 
Table 14.3.5.2 
Summary of Treatment-Related Treatment Emergent 
Adverse Events Leading to Permanent Discontinuation 
of IMP 
Safety Analysis Set 
Table 14.3.5.3 
Summary of Treatment Emergent Adverse Events 
Leading to IMP Dose Reduction Excluding Permanent 
Discontinuation and by Resolution and Overall 
Safety Analysis Set 
Table 14.3.5.4 
Summary of Treatment-Related Treatment Emergent 
Adverse Events Leading to IMP Dose Reduction 
Excluding Permanent Discontinuation and by 
Resolution and Overall 
Safety Analysis Set 
Table 14.3.5.5 
Summary of Treatment Emergent Adverse Events 
Leading to Temporary IMP Dose Reduction by 
Resolution and Overall 
Safety Analysis Set 
Table 14.3.5.6 
Summary of Treatment-Related Treatment Emergent 
Adverse Events Leading to Temporary IMP Dose 
Reduction by Resolution and Overall 
Safety Analysis Set 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 34 of 36 
  
 
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Table Number 
Title 
Analysis Set 
Table 14.3.5.7 
Summary of Treatment Emergent Adverse Events 
Leading to Permanent IMP Dose Reduction Excluding 
Permanent Discontinuation and by Resolution and 
Overall 
Safety Analysis Set 
Table 14.3.5.8 
Summary of Treatment-Related Treatment Emergent 
Adverse Events Leading to Permanent IMP Dose 
Reduction Excluding Permanent Discontinuation and 
by Resolution and Overall 
Safety Analysis Set 
Table 14.3.6.1 
Summary of Columbia-Suicide Severity Rating Scale by 
Type 
Safety Analysis Set 
Table 14.3.7.1 
Summary of Laboratory Safety Parameters – 
Hematology 
Safety Analysis Set 
Table 14.3.7.2 
Shift Table for Hematology Laboratory Parameters – 
Based on Reference Ranges 
Safety Analysis Set 
Table 14.3.7.3 
Shift Table for Hematology Laboratory Parameters – 
Based on Toxicity Limits  
Safety Analysis Set 
Table 14.3.7.4 
Summary of Laboratory Safety Parameters – 
Biochemistry 
Safety Analysis Set 
Table 14.3.7.5 
Shift Table for Biochemistry Laboratory Parameters – 
Based on Reference Ranges  
Safety Analysis Set 
Table 14.3.7.6 
Shift Table for Biochemistry Laboratory Parameters – 
Based on Toxicity Limits 
Safety Analysis Set 
Table 14.3.7.7 
Shift Table for CrCl – Based on Derived Grades 
Safety Analysis Set 
Table 14.3.7.8 
Summary of Liver Parameter Flags 
Safety Analysis Set 
Table 14.3.7.9 
Summary of Drug Screen 
Safety Analysis Set 
Table 14.3.7.10 
Summary of Pregnancy Test  
Safety Analysis Set 
Table 14.3.8.1 
Summary of Vital Signs  
Safety Analysis Set  
Table 14.3.8.2 
Incidence of Clinically Significant Changes from 
Baseline for Vital Signs 
Safety Analysis Set 
Table 14.3.8.3 
Incidence of Defined Flagged Vital Signs 
Safety Analysis Set 
Table 14.3.8.4 
Summary of ECG Parameters 
Safety Analysis Set 
Table 14.3.8.5 
Incidence of Defined Flagged ECG Parameter Values 
Safety Analysis Set 
 
 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 35 of 36 
  
 
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Table 10 
List of Listings 
Listing Number 
Title 
Analysis Set 
Listing 16.2.1.1 
Screen Failures 
All Screen Failure Participants 
Listing 16.2.1.2 
Participant Disposition – End of Treatment Period 
Safety Analysis Set 
Listing 16.2.1.3 
Inclusion/Exclusion Criteria Not Met 
Safety Analysis Set  
Listing 16.2.1.4 
Visit Dates 
Safety Analysis Set 
Listing 16.2.2.1 
Major and Critical Protocol Deviations 
Randomized Participants 
Listing 16.2.2.2 
All Protocol Deviations 
Randomized Participants 
Listing 16.2.4.1 
Demography 
Safety Analysis Set 
Listing 16.2.4.2 
Baseline Characteristics 
Safety Analysis Set 
Listing 16.2.4.3 
Psychiatric History 
Safety Analysis Set 
Listing 16.2.4.4 
Significant Non-Psychiatric Medical or Surgical History 
Safety Analysis Set 
Listing 16.2.4.5 
Concomitant Antipsychotic Medications 
Safety Analysis Set 
Listing 16.2.4.6 
Other Concomitant Medications 
Safety Analysis Set 
Listing 16.2.5.1 
Treatment Compliance 
Safety Analysis Set  
Listing 16.2.6.1 
PANSS Syndromes 
Full Analysis Set 
Listing 16.2.6.2 
PANSS Individual Syndrome Responses 
Full Analysis Set 
Listing 16.2.6.3 
PANSS Total Score and Subscale Scores 
Full Analysis Set 
Listing 16.2.6.4 
CGI-S and CGI-I 
Full Analysis Set 
Listing 16.2.6.5 
PANSS Marder Factors Scores 
Full Analysis Set 
Listing 16.2.6.6 
BACS Verbal Memory and Verbal Fluency 
Full Analysis Set 
Listing 16.2.6.7 
BACS Composite and Domain Scores 
Full Analysis Set 
Listing 16.2.6.8 
Multidimensional Psychological Questionnaires 
Safety Analysis Set 
Listing 16.2.6.9 
Plasma Concentrations 
Safety Analysis Set 
Listing 16.2.6.10 
Plasma Concentrations of Concomitant Antipsychotic 
Medications 
Safety Analysis Set 
Listing 16.2.7.1 
Treatment Emergent Adverse Events 
Safety Analysis Set 
Listing 16.2.7.2 
Pre-Treatment Adverse Events 
Safety Analysis Set 
Listing 16.2.7.3 
Participants Experiencing Treatment Emergent Adverse 
Events by System Organ Class and Preferred term 
Safety Analysis Set 
Listing 16.2.7.4 
Serious Adverse Events 
Safety Analysis Set 
Listing 16.2.8.1 
Laboratory Parameters 
Safety Analysis Set 
Listing 16.2.8.2 
Abnormal Laboratory Parameters by Participant 
Safety Analysis Set 
Listing 16.2.8.3 
Abnormal Laboratory Parameters by Parameter 
Safety Analysis Set 


Trial Code: GWAP19030 
EudraCT Number:  2019-003369-16 
ClinicalTrials.gov Identifier: NCT04421456 
SAP, Final v1.0 Date: 08 April 2022 
 
 
 
 
 
GWAP19030 
 
Page 36 of 36 
  
 
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Listing Number 
Title 
Analysis Set 
Listing 16.2.8.4 
Laboratory Comments 
Safety Analysis Set 
Listing 16.2.8.5 
Laboratory Liver Parameters 
Safety Analysis Set 
Listing 16.2.8.6 
Laboratory Reference Ranges and Toxicity Limits 
Safety Analysis Set 
Listing 16.2.9.1 
Vital Signs – Blood Pressures  
Safety Analysis Set 
Listing 16.2.9.2 
Vital Signs – Heart Rate, Respiratory Rate and 
Temperature 
Safety Analysis Set 
Listing 16.2.9.3 
Vital Signs – Height, Weight, Waist Circumference and 
BMI 
Safety Analysis Set 
Listing 16.2.9.4 
Potentially Clinically Significant Changes from Baseline 
for Vital Signs 
Safety Analysis Set 
Listing 16.2.10.1 
ECG Data – Part 1 
Safety Analysis Set 
Listing 16.2.10.2 
ECG Data – Part 2 
Safety Analysis Set 
Listing 16.2.10.3 
 
Mealtimes 
Safety Analysis Set 
Listing 16.2.10.4 
Physical Examination 
Safety Analysis Set