A Phase IIb Study of the Safety and Efficacy of Nabiximols in Subjects With Spasticity Due to Neuromyelitis Optica Spectrum Disorders: A Double-blind, Randomized, Placebo-Controlled, Crossover Study

Exclusion criteria

• Consumption of cannabis herb or other cannabinoid-based drugs within 30 days prior to study entry.
• Unwillingness to abstain from consumption of cannabis herb or other cannabinoid-based drugs for the duration of the study.
• Known or suspected hypersensitivity or adverse reaction (including psychiatric adverse reactions) to cannabinoids or cannabinoid products, ethanol, peppermint oil or propylene glycol.
• Currently receiving a prohibited medication and unwilling or unable to stop for the duration of the study. Prohibited medications include: CYP3A4 inhibitors: clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, etc.; CYP3A4 inducers: rifampicin, phenobarbital, phenytoin, St. John's Wort. Of note, the CYP3A4 inducer carbamazepine is permitted, but a stable dosage must be maintained throughout the study (no as needed dosing permitted). Other prohibited medications: regular levodopa (Sinemet, Sinemet Plus, Levodopa, L-dopa, Madopar, Benserazide), sildenafil (Viagra), fentanyl, or antiarrhythmic medications.
• Receipt of an investigational medicinal product or participation in a therapeutic clinical trial within 30 days prior to the initial visit
• Received a Botulinum Toxin injection within four months prior to the screening visit or unwillingness to stop receiving Botulinum Toxin injections for the relief of spasticity for the duration of the study.
• Personal medical history of schizophrenia, severe personality disorders, other major psychotic disorders, or other major psychiatric disorders other than depression and anxiety.
• Family history in 1st degree relatives of schizophrenia or other psychotic disorders.
• Hospitalization for depression or anxiety within the 2 years prior to the screening visit.
• A documented history of attempted suicide or suicidal ideation of category 4 or 5 according to the Columbia Suicide Severity Rating Scale (C-SSRS) screening, OR if in the Investigator's judgment, the participant is at risk for a suicide attempt.
• Known or suspected history of a substance use disorder or heavy alcohol consumption excluding tobacco use disorder or cannabis use not meeting criteria for cannabis use disorder.
• History of myocardial infarction or clinically significant ischemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure. .
• Significant renal or hepatic impairment, either in the opinion of the investigator, or by the following laboratory screening values: AST or ALT \> 2 × upper limit of normal (ULN); Total bilirubin \> 2 × ULN (unless due to Gilbert's syndrome); BUN \> 2 × upper limit of normal (ULN)
• History of epilepsy or recurrent seizures.