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
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: GWP42003-P; Placebo
Intervention description: 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; oral solution containing the excipients sesame oil and anhydrous ethanol, with added β-carotene, sweetener (sucralose), and strawberry flavoring
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 95.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: GWP42003-P; adjunctive therapy; inadequate response to ongoing antipsychotic treatment

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.
    

Eligibility criteria:

        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