Abuse Potential of Intravenous Remimazolam Compared to Midazolam and Placebo in Recreational CNS Depressant Users

Exclusion Criteria

• •1. Drug or alcohol dependence within the 12 months prior to Screening (except nicotine), as defined by the Diagnostic and Statistical Man ual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), or any self-reported dependence or "addiction" within the subject's lifetime (except nicotine or caffeine).
• •2. Subjects who have ever been in treatment for substance use disorder(s) (except smoking cessation).
• •3. History or presence of any clinically significant cardiac, psychiatric, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, renal, or other major disease at Screening, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results, including subjects with chronic renal failure or congestive heart failure.
• •4. In the opinion of the investigator, the subject was at risk for respiratory depression, including subjects with obstructive apnea, upper airway obstruction, chronic obstructive pulmonary disease, acute or severe bronchial asthma, hypercarbia, or other severe cardio-respiratory disease.
• •5. Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
• •6. History of, or evidence at the time for, suicidal ideation with intent, with or without a plan or method, in the past 5 years or suicidal behavior in their lifetime or those who were actively suicidal based on the Columbia-Suicide Severity Rating Scale (C-SSRS).
• •7. Unexplained significant and recent loss of consciousness, or history of significant head trauma with loss of consciousness.
• •8. Reported history of acute narrow-angle glaucoma.
• •9. Required concomitant treatment with any prescription or non-prescription medications (with the exception of hormonal contraceptives, hormone replacement, and acetaminophen) or natural health products (herbal remedies), including strong cytochrome P450 (CYP) 3A4 inhibitors or respiratory depressants, or could not safely discontinue these medications within 7 days or 5 half -lives (whichever is longer) prior to receiving study drug in the Qualification Phase and for the Duration of the study.
• •10. Subject was using an investigational drug or device or had used such within the 30 days (or 5 half-lives, whichever is longer) prior to first drug administration in the Qualification Phase.
• •11. Female subjects who were pregnant or lactating or who were planning to become pregnant within 14 days of last study drug administration.
• •12. Subject had a prior history of any significant adverse reactions (including rash) to benzodiazepines and/or flumazenil, or known allergies to midazolam and/or flumazenil, or formulation components.
• •13. Subject had unsuitable or difficult venous access or was unwilling or unable to undergo catheter insertion.
• •14. Subject was an employee of the sponsor or research site personnel directly affiliated with this study or their immediate family member defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
• •15. A subject who, in the opinion of the investigator, was considered unsuitable or unlikely to comply with the study protocol for any reason (in each case, the investigator had to specify the reason).