Dose-Finding Safety Study Evaluating Remimazolam (CNS 7056) in Patients Undergoing Diagnostic Upper GI Endoscopy
Condition: Procedural Sedation; Endoscopy
Intervention: CNS 7056; Midazolam
Intervention description: Administered as a single intravenous injection by a syringe driver over 1 minute; Administered as a single intravenous injection by a syringe driver over 1 minute
Intervention MeSH terms: Midazolam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: CNS 7056; Procedural Sedation; Sedation; Endoscopy

Summary:

      The purpose of this study was to assess the safety and efficacy of CNS 7056 as a procedural
      sedative at three dose levels compared to midazolam during a diagnostic upper GI endoscopy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients, aged 18 to 65 years inclusive, scheduled to undergo
             diagnostic upper GI endoscopy.

          -  American Society of Anesthesiologists Physical Status (ASA PS) Score I or II.

          -  Weight range 60 to 120 kg inclusive.

          -  Body mass index (BMI) 18 to < 30 kg/m2.

          -  Patients with no clinically significant abnormalities in 12 lead ECG recorded at
             Screening.

          -  Female with a negative serum human chorionic gonadotropin (hCG) pregnancy test result
             at Screening and negative urine hCG pregnancy test result on Day 1 before the
             endoscopy procedure.

          -  Patients with negative drugs of abuse serum result at Screening and negative drugs of
             abuse urine result on Day 1 before the endoscopy procedure.

          -  Patient has a negative serum ethanol test result at Screening and a negative ethanol
             saliva test result on Day 1 before the endoscopy procedure.

          -  Patient voluntarily signs and dates an informed consent form (ICF) that is approved by
             an investigational review board (IRB) prior to the conduct of any study procedure.

          -  Patient is willing and able to comply with study requirements and return for a Follow
             up Visit (Visit 3 ± 1 day) after the endoscopy procedure.

        Exclusion Criteria:

          -  Patients with a suspected upper GI bleed an conditions predisposing to hemorrhage at
             the discretion of the investigator.

          -  Has a known sensitivity to benzodiazepines, flumazenil, or anesthetic agents, or a
             medical condition such that these agents are contraindicated.

          -  Patients with evidence of uncontrolled renal, hepatic, central nervous system,
             respiratory, cardiovascular, or metabolic dysfunction, in the opinion of the
             investigator or medical monitor.

          -  Patients taking an agent that inhibits cytochrome P450 subtype 3A4 (CYP3A4) or
             patients who have taken such an agent within 14 days prior to study start or within
             the duration of 7 half lives of the drug, whichever is longer.

          -  Patients in receipt of any investigational drug within 30 days or less than 7 half
             lives (whichever is longer) before the start of the study, or scheduled to receive one
             during the study period.

          -  Chronic use of benzodiazepines for any indication (eg, insomnia, anxiety, spasticity).

          -  Has known or suspected history of alcoholism or drug abuse or misuse within 2 years of
             Screening or evidence of tolerance or physical dependence before dosing with study
             drug.

          -  Patients with clinically significant findings at Screening that, in the investigator's
             opinion, should exclude them from the study.

          -  Patients with a history of laboratory results that show the presence of hepatitis B
             surface antigen (HBs Ag), hepatitis C antibody (HCV Ab), or human immunodeficiency
             virus (HIV).

          -  Patients with an inability to communicate well in English with the investigator.

          -  Lactating female patients.

          -  Patients in whom management of airway is judged to be difficult due to:

               -  obesity (weight > 120 kg, or BMI ≥ 30 kg/m2),

               -  thyro mental distance ≤ 4 cm ("short neck"), or

               -  Mallampati score of 4 (Appendix IV).