Clinical trial NCT04421456: 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
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: GWP42003-P
adjunctive therapy
inadequate response to ongoing antipsychotic treatment
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-06-09
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Least Square Mean Change From Baseline in the Positive and Negative Symptoms Scale (PANSS) Total (PANSS-T) Score
timeFrame: Baseline up to Week 12
measure: Least Square Mean Change From Baseline in the PANSS Positive Subscale (PANSS-P) Score
timeFrame: Baseline up to Week 12
measure: Least Square Mean Change From Baseline in the PANSS Negative Subscale (PANSS-N) Score
timeFrame: Baseline up to Week 12
measure: Least Square Mean Change From Baseline in the PANSS General Subscale (PANSS-G) Score
timeFrame: Baseline up to Week 12
measure: Least Square Mean Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Score
timeFrame: Baseline up to Week 12
measure: Number of Participants With Minimally or Better Clinical Global Impression of Improvement (CGI-I) Score at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Mean Change From Baseline in Body Weight
timeFrame: Baseline up to Week 12
measure: Mean Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline up to Week 12
measure: Mean Change From Baseline in Waist Circumference
timeFrame: Baseline up to Week 12
measure: Mean Change From Baseline in Blood Pressure
timeFrame: Baseline up to Week 12
measure: Mean Change From Baseline in Heart Rate
timeFrame: Baseline up to Week 12
measure: Mean Change From Baseline in Respiratory Rate
timeFrame: Baseline up to Week 12
measure: Mean Change From Baseline in Temperature
timeFrame: Baseline up to Week 12
measure: Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Test Results
timeFrame: Day 85
measure: Number of Participants With Defined Flagged Electrocardiogram (ECG) Parameter Values
timeFrame: Day 85
measure: Number of Participants With Suicidal Ideation or Behavior Based on The Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline (screening) up to Day 85
Other outcomes:
Locations:
city: Bentonville
country: United States
facility: Clinical Trial Site
state: Arkansas
city: Little Rock
country: United States
facility: Clinical Trial Site
state: Arkansas
city: Garden Grove
country: United States
facility: Clinical Trial Site
state: California
city: Lemon Grove
country: United States
facility: Clinical Trial Site
state: California
city: Oakland
country: United States
facility: Clinical Trial Site
state: California
city: Pico Rivera
country: United States
facility: Clinical Trial Site
state: California
city: Largo
country: United States
facility: Clinical Trial Site
state: Florida
city: Lauderhill
country: United States
facility: Clinical Trial Site
state: Florida
city: Tampa
country: United States
facility: Clinical Trial Site
state: Florida
city: Lincolnwood
country: United States
facility: Clinical Trial Site
state: Illinois
city: Shreveport
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Trial Site
state: Nevada
city: Berlin
country: United States
facility: Clinical Trial Site
state: New Jersey
city: Cedarhurst
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Rochester
country: United States
facility: Clinical Trial Site
state: New York
city: Beachwood
country: United States
facility: Clinical Trial Site
state: Ohio
city: Richardson
country: United States
facility: Clinical Trial Site
state: Texas
city: Belchatow
country: Poland
facility: Clinical Trial Site
city: Gdansk
country: Poland
facility: Clinical Trial Site
city: Kielce
country: Poland
facility: Clinical Trial Site
city: Kobierzyce
country: Poland
facility: Clinical Trial Site
city: Poznan
country: Poland
facility: Clinical Trial Site
city: Torun
country: Poland
facility: Clinical Trial Site
city: Wroclaw
country: Poland
facility: Clinical Trial Site
city: Wroclaw
country: Poland
facility: Clinical Trial Site
city: Belgrade
country: Serbia
facility: Clinical Trial Site#1
city: Belgrade
country: Serbia
facility: Clinical Trial Site#2
city: Kovin
country: Serbia
facility: Clinical Trial Site#1
city: Kovin
country: Serbia
facility: Clinical Trial Site#2
city: Kragujevac
country: Serbia
facility: Clinical Trial Site#1
city: Kragujevac
country: Serbia
facility: Clinical Trial Site#2
city: Kragujevac
country: Serbia
facility: Clinical Trial Site#3
city: Nis
country: Serbia
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Oviedo
country: Spain
facility: Clinical Trial Site
city: Salamanca
country: Spain
facility: Clinical Trial Site
city: Valladolid
country: Spain
facility: Clinical Trial Site
Study officials:
References: