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 Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: GWP42003-P
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 to 55 years of age at the time of signing the Informed Consent Form (ICF) Willing and able to give informed consent for participation in the trial Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of schizophrenia, confirmed by the Mini International Neuropsychiatric Interview (MINI) Clinically stable outpatient Positive and Negative Symptoms Scale (PANSS) Total (PANSS-T) score of ≥ 60 and < 110 at screening and baseline visits 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 Score ≥ 4 (at least moderately ill) on the Clinical Global Impression of Severity (CGI-S) at screening visit. Undergoing treatment with at least 1 antipsychotic medication with no change in dosing, supported by documentation, for at least 8 weeks prior to screening and no change in antipsychotic medication dosing planned throughout the trial Taking a maximum of 2 antipsychotic medications. For participants taking oral antipsychotic medications only, the sum of primary and secondary antipsychotic medications is ≤ 30 milligrams (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. Documented response (at least partially) to treatment with current antipsychotic medications (e.g., treatment of recent exacerbation of psychotic symptoms) 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. Exclusion Criteria: Diagnosis and Psychiatric History 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. 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 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. A positive drug screen for opiates, methadone, cocaine, amphetamines (including ecstasy), or barbiturates; a repeat drug screen may be done to verify the result. 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 Treatment History 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. 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 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 Tardive dyskinesia (TD) that is moderate to severe (i.e., a score of > 21 on the dyskinesia subscale of the Extrapyramidal Symptom Rating Scale [ESRS] at screening) or requires treatment Any other significant disease, disorder, pending court proceedings or social circumstances which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, may influence the result of the trial, or may affect the participant's ability to take part in the trial. Other Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal product, such as sesame seed oil 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) Currently using or within 3 months of screening has used cannabidiol (CBD) oil or purified CBD preparations and is unwilling to abstain for the duration of the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GWP42003-P 300 mg<br>GWP42003-P 300 milligrams (mg) per day | Drug: GWP42003-P<br>* 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<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* oral solution containing the excipients sesame oil and anhydrous ethanol, with added β-carotene, sweetener (sucralose), and strawberry flavoring<br>|
| Experimental: GWP42003-P 1000 mg<br>GWP42003-P 1000 mg per day | Drug: GWP42003-P<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Least Square Mean Change From Baseline in the Positive and Negative Symptoms Scale (PANSS) Total (PANSS-T) Score | The PANSS-T is a medical scale used for measuring symptom severity of participants with schizophrenia or related psychotic disorder. 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, where higher scores represent worse outcome. The least square mean change from baseline is being reported and negative values indicate an improvement in outcome. | Baseline up to Week 12 | 
| Least Square Mean Change From Baseline in the PANSS Positive Subscale (PANSS-P) Score | The PANSS 'P' Scale was 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. Individual items are rated on a 7-point scale, where 1 = absent and 7 = extreme. The least square mean change from baseline is being reported and negative values indicate an improvement in outcome. | Baseline up to Week 12 | 
| Least Square Mean Change From Baseline in the PANSS Negative Subscale (PANSS-N) Score | 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 withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. Individual items are rated on a 7-point scale, where 1 = absent and 7 = extreme. The least square mean change from baseline is being reported and negative values indicate an improvement in outcome. | Baseline up to Week 12 | 
| Least Square Mean Change From Baseline in the PANSS General Subscale (PANSS-G) Score | 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. Individual items are rated on a 7-point scale, where 1 = absent and 7 = extreme. The least square mean change from baseline is being reported and negative values indicate an improvement in outcome. | Baseline up to Week 12 | 
| Least Square Mean Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Score | 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 least square mean change from baseline is being reported and negative values indicate an improvement in outcome. | Baseline up to Week 12 | 
| Number of Participants With Minimally or Better Clinical Global Impression of Improvement (CGI-I) Score at Week 12 | The CGI-I is a 7-point scale used to rate the improvement of participants' condition at the time of assessment. Compared to the patient's condition at baseline, the participants' condition was rated as 1 = very much improved since initiation of treatment; 2 = much improved; 3 = minimally improved; 4 = no change from baseline; 5 = minimally worse; 6 = much worse; 7 = very much worse since the initiation of treatment. Higher scores indicate a worse outcome. The number of participants with minimally or better improvements (score of 3 or better) are being reported. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Body Weight |  | Baseline up to Week 12 | 
| Mean Change From Baseline in Body Mass Index (BMI) |  | Baseline up to Week 12 | 
| Mean Change From Baseline in Waist Circumference |  | Baseline up to Week 12 | 
| Mean Change From Baseline in Blood Pressure |  | Baseline up to Week 12 | 
| Mean Change From Baseline in Heart Rate |  | Baseline up to Week 12 | 
| Mean Change From Baseline in Respiratory Rate |  | Baseline up to Week 12 | 
| Mean Change From Baseline in Temperature |  | Baseline up to Week 12 | 
| Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Test Results |  | Day 85 | 
| Number of Participants With Defined Flagged Electrocardiogram (ECG) Parameter Values |  | Day 85 | 
| Number of Participants With Suicidal Ideation or Behavior Based on The Columbia Suicide Severity Rating Scale (C-SSRS) | The C-SSRS is a short questionnaire that is used to assess suicidal ideation (5 questions) and behavior (5 questions) since last patient visit. The questionnaire is completed by participants answering yes or no to each question. | Baseline (screening) up to Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GWP42003-P, adjunctive therapy, inadequate response to ongoing antipsychotic treatment