Study of the Safety and Efficacy of Nabiximols Oromucosal Spray Versus Placebo in Patients With Post-traumatic Stress Disorder

Inclusion Criteria:

• Meets Diagnostic and Statistical Manual of Mental Disorders, Volume 5 (DSM-5) criteriafor post-traumatic stress disorder (PTSD), confirmed on the basis of the MiniInternational Neuropsychiatric Interview (MINI)
• If currently taking a selective serotonin reuptake inhibitor (SSRI) orserotonin-norepinephrine reuptake inhibitor (SNRI) for the treatment of PTSD,SSRI/SNRI doses should be consistent with approved labelling and have been stable forat least 6 weeks prior to Visit 1 with no more than 1 SSRI/SNRI.
• If not currently taking a SSRI or SNRI, should not have received treatment with eithera SSRI or SNRI for at least 6 weeks prior to Visit 1 and is not planning to startadditional pharmacotherapy during the study
• Exhibits significant PTSD symptoms and associated impairment (as reflected byClinician Administered PTSD Scale [CAPS-5] ≥ 27 and Clinical Global ImpressionsSeverity [CGI-S] ≥ 4 at Visit 1), which should have persisted over a period of atleast 3 months prior to Visit 1
• Willing to allow the responsible authorities to be notified of participation in thetrial, if mandated by local law
• Willing to allow his or her primary care practitioner (if they have one) andconsultant (if they have one) to be notified of participation in the trial, if theprimary care practitioner/consultant is different to the investigator

Exclusion Criteria:

• Is at risk of suicide as evidenced by a history of suicide attempt(s) in the 2 yearsprior to Visit 1 or answering yes on item 4 or 5 of the Columbia-Suicide SeverityRating Scale (C-SSRS) in the month prior to Visit 1
• Is currently involved in any legal action that relates to the diagnosis of PTSD or thetraumatic events that gave rise to the disease
• Has cognitive impairment that in the opinion of the investigator may interfere withparticipation in the study or ability to complete assessments or report treatmenteffects
• Has any history of psychosis (including schizophrenia, schizophreniform disorder,schizoaffective disorder, or substance-induced psychosis), or bipolar disorder basedon an assessment using the MINI.
• Participants who have an index trauma before age 18 and no other traumatic experienceswhich could relate/identify as being part of their PTSD
• Has taken cannabis or a cannabis derived product for medicinal or recreationalpurposes at any time in the past and developed significant adverse experiences relatedto cannabis use per history and investigator judgment
• Has severe depressive symptoms as per the investigator's judgment or a score ≥ 20 onthe Patient Health Questionnaire-9 (PHQ-9) at Visit 1
• Has a history of any degree of DSM-5 cannabis or other substance use disorder, ormoderate to severe alcohol use disorder within 6 months prior to Visit 1. Participantswith Nicotine Use Disorder are allowed to enroll.
• Has any known or suspected hypersensitivity to cannabinoids or any of the excipientsof the investigational medicinal product
• Has recently taken nabiximols, cannabis, or a cannabis-derived product for medicinalor recreational purposes as reflected by a positive Δ9-tetrahydrocannabinol (THC)urine test at Visit 1
• Currently taking 1 of a number of specified psychotropic medications, where there is apotential for pharmacodynamic interactions. Participants taking any medication withpsychoactive properties not currently on the list of prohibitive medications may beconsidered for enrollment only after consultation with a GW medical representative.
• Has experienced myocardial infarction or clinically significant cardiac dysfunctionwithin the 12 months prior to Visit 1 or has a cardiac disorder that, in the opinionof the investigator, would put the participant at risk of a clinically significantarrhythmia or myocardial infarction
• Positive serology panel (including hepatitis B surface antigen [HBsAg] and hepatitis Cvirus [HCV] antibody)
• Positive human immunodeficiency virus (HIV) antibody/p24 antigen screens
• Has a diastolic blood pressure of < 50 millimeters of mercury (mmHg) or > 105 mmHg orsystolic blood pressure < 90 mmHg or > 150 mmHg (when measured in a sitting positionat rest for 5 minutes) or a postural drop in the systolic blood pressure of > 20 mmHgat Visit 1
• Has clinically significant impaired renal function at Visit 1, as evidenced by anestimated creatinine clearance lower than 50 milliliters per minute (mL/min)
• Has serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 ×upper limit of normal (ULN) at Visit 1
• Male and fertile (i.e., after puberty unless permanently sterile by bilateralorchiectomy) unless willing to ensure that he uses male contraception (condom orvasectomy) or remains sexually abstinent during the trial and for 3 months thereafter
• Female and of childbearing potential (i.e., following menarche and until becomingpostmenopausal for ≥ 12 consecutive months unless permanently sterile by hysterectomy,bilateral salpingectomy, or bilateral oophorectomy) unless willing to ensure that sheuses a highly effective method of birth control (e.g., intrauterinedevice/hormone-releasing system, bilateral tubal occlusion, vasectomized partner, orsexual abstinence) during the trial and for 3 months thereafter. Participants usingcombined hormonal methods or a progestogen-only pill or injection or implant shoulduse an additional barrier method such as a male condom or diaphragm during the trialand for 3 months thereafter.
• Female and pregnant (positive pregnancy test at Visit 1), lactating, or planningpregnancy during the course of the trial or within 3 months thereafter
• Has participated in an interventional or non-interventional clinical trial within the 30 days prior to Visit 1
• Has donated blood during the 3 months prior to Visit 1 and is unwilling to abstainfrom donation of blood during the trial
• Has been previously randomized into this trial
• Any abnormalities identified following a physical examination, clinical laboratory,serology, or other applicable screen procedures that, in the opinion of theinvestigator, would jeopardize the safety of the participant or the conduct of thestudy if they took part in the trial
• Participants who are currently participating in a trauma-focused psychotherapy areineligible to participate in the trial. Participants who are participating in otherforms of psychotherapy (or none at all) must agree to continue (or not start) therapyduring the trial. Additional exclusion criterion at Visit 2 (Day 1, pre-randomization):
• Exhibited a CAPS-5 score < 27 at Visit 2, or a reduction in CAPS-5 score of ≥ 30% atVisit 2 relative to Visit 1
• Did not complete the writing exercise during the screening period