Multiple Dose Safety and Efficacy Study Evaluating CNS 7056 Versus Midazolam in Patients Undergoing Colonoscopy

• Safety by measurement of Adverse Events. [ Time Frame: From start of study drug injection to patient discharge (approx. 3 hours) ] [ Designated as safety issue: Yes ]
• Measurement of Sedation levels and duration. [ Time Frame: From start of study drug injection to patient discharge (approx. 3 hours) ] [ Designated as safety issue: No ]
• Measurement of Procedure recall and Cognitive function. [ Time Frame: From prior to study drug injection until patient completes follow-up visit (approx. 4 days) ] [ Designated as safety issue: No ]
• Assessment of standard Pharmacokinetic parameters of CNS 7056 in human plasma. [ Time Frame: From prior to study drug injection until patient discharge (approx. 3 hours) ] [ Designated as safety issue: No ]

The purpose of this dose-response study is to assess the safety and efficacy of CNS 7056 compared with midazolam to maintain suitable sedation levels in patients undergoing colonoscopy.

This is a double-blind, randomized, parallel group, dose-response study to assess the safety and efficacy of three dose levels of CNS 7056 compared with midazolam to maintain suitable sedation levels in patients undergoing colonoscopy.

Safety assessment will include physical examinations, vital signs, ECGs, pulse oximetry measurements, capnography, clinical chemistry and hematology laboratory tests, routine drug and ethanol screening, urinalysis, pregnancy test, pain on injection using a verbal scale, and monitoring of adverse events.

• Drug: A. CNS 7056
  Initial low dose plus supplemental doses as necessary.
  Other Name: CAS No. 1001415-66-2
• Drug: B. CNS 7056
  Initial intermediate dose plus supplemental doses as necessary.
  Other Name: CAS No. 1001415-66-2
• Drug: C. CNS 7056
  Initial high dose plus supplemental doses as necessary.
  Other Name: CAS No. 1001415-66-2
• Drug: D. Midazolam
  Initial standardized dose plus supplemental doses as necessary.
  Other Name: CAS No. 59467-96-8

• Experimental: A. CNS 7056
  Intervention: Drug: A. CNS 7056
• Experimental: B. CNS 7056
  Intervention: Drug: B. CNS 7056
• Experimental: C. CNS 7056
  Intervention: Drug: C. CNS 7056
• Active Comparator: D. Midazolam
  Intervention: Drug: D. Midazolam

Inclusion Criteria:

• Male and female patients 18 to 70 years of age scheduled to undergo a standard colonoscopy
• American Society of Anesthesiologists Physical Status (ASA-PS) Score I, II, or III
• Weight range 55 to 130 kg inclusive
• BMI 18 ≤33 kg/m2

Exclusion Criteria:

• Expected duration of colonoscopy >30 minutes
• Patients with a suspected or diagnosed pathology of the lower GI tract that would add to the risk of colonoscopy, such as strictures or active inflammatory bowel disease
• ASA III patients with history of sleep apnea
• ASA III patients with obesity (BMI ≥30 kg/m2)
• Patients with evidence of uncontrolled renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction, or other clinically significant findings at screening that, in the investigator's or medical monitor's opinion, should exclude them from the study
• Patients with a known sensitivity to benzodiazepines, flumazenil, opioids, naloxone, or a medical condition such that these agents are contraindicated
• Patients in whom management of airway is judged to be difficult due to thyro-mental distance ≤4 cm ("short neck") or Mallampati score of 4