A Study of AQUAVAN® Injection Versus Midazolam HCl for Sedation in Patients Undergoing Elective Colonoscopy

• Secondary Efficacy Endpoints
• Time to Fully Recovered from end of procedure
• Time to Fully Alert from end of procedure
• Change from baseline DSST score over time during recovery period
• Duration and percent of time when a patient's Modified OAA/S score is at each level between the first dose of study medications and Fully Alert, inclusive
• Duration of sedation
• Number of doses of study medication administered for the procedure
• Time to sedation
• Time to reach splenic flexure, hepatic flexure, cecum, and end of procedure
• Number of repositionings
• Number of procedure interruptions due to inadequate sedation
• Patient's rating of experience after Fully Recovered
• Patient's rating at 24 hour post discharge telephone survey
• Investigator's rating at end of procedure
• Blinded evaluator's rating after patient is Fully Recovered
• Safety Endpoints
• Nature, frequency, severity, relationship to treatment, and outcome of all adverse events
• Airway assistance
• Sedation-related adverse events
• Laboratory parameters and vital signs
• Concomitant medications

• Secondary Efficacy Endpoints
• • Time to Fully Recovered from end of procedure
• • Time to Fully Alert from end of procedure
• • Change from baseline DSST score over time during recovery period
• • Duration and percent of time when a patient’s Modified OAA/S score is at each level between the first dose of study medications and Fully Alert, inclusive
• • Duration of sedation
• • Number of doses of study medication administered for the procedure
• • Time to sedation
• • Time to reach splenic flexure, hepatic flexure, cecum, and end of procedure
• • Number of repositionings
• • Number of procedure interruptions due to inadequate sedation
• • Patient’s rating of experience after Fully Recovered
• • Patient’s rating at 24 hour post discharge telephone survey
• • Investigator’s rating at end of procedure
• • Blinded evaluator’s rating after patient is Fully Recovered
• Safety Endpoints
• • Nature, frequency, severity, relationship to treatment, and outcome of all adverse events
• • Airway assistance
• • Sedation-related adverse events
• • Laboratory parameters and vital signs
• • Concomitant medications

This study was designed to demonstrate that AQUAVAN® is effective in providing adequate sedation in patients undergoing colonoscopy as well as to assess the safety profile of AQUAVAN versus that of midazolam. Prior to the procedure, patients received fentanyl citrate for pain management followed five minutes later by AQUAVAN® Injection for sedation. Throughout the procedure, study personnel assessed the patient's vital signs and depth of sedation. After the procedure, the patient, physician, and an evaluator were asked to complete satisfaction surveys.

This is a randomized, open-label study designed to assess the safety and efficacy of AQUAVAN® Injection versus midazolam HCl following pretreatment with an analgesic, fentanyl citrate injection, in producing sedation in patients undergoing colonoscopy. Randomization will be stratified by site. Following completion of pre-procedure sedation assessments, patients will be randomly assigned to 1 of the 2 i.v. treatment groups at a 3:1 (AQUAVAN® Injection: midazolam HCl) allocation ratio. All study patients, irrespective of treatment group assignment, will receive fentanyl citrate injection as an analgesic pretreatment. Supplemental doses of fentanyl citrate injection may be administered if the patient reports pain or if inadequate analgesia is present as demonstrated by increased heart rate and/or blood pressure in the presence of adequate sedation. At no time should fentanyl citrate injection be administered to increase sedation levels. AQUAVAN® Injection and midazolam HCl will be administered to induce a state of adequate sedation, defined as a Modified Observer's Assessment of Alertness / Sedation (OAA/S) score of 4 or less. Supplemental doses will be administered to increase depth or duration of sedation. Supplemental doses will not be administered if the Modified OAA/S score is 2 or less or if there is no purposeful response to stimulation. The depth of sedation will be measured by the Modified OAA/S scale, a validated measure. Patient and Investigator assessments will be used to confirm the depth of sedation provided met the goals of sedation, reduction of anxiet, and reduced awareness.

• Colonoscopy
• Colon Polyps

Inclusion Criteria:

• Patient provided a signed/dated Informed Consent and HIPAA authorization after receiving a full explanation of the extent and nature of the study;
• Patient, if female, were surgically sterile, postmenopausal or non-pregnant and non lactating using an acceptable method of birth control for at least 1 month prior to dosing, with a negative urine pregnancy test result at screening and predose periods; and
• Patient met American Society of Anesthesiologists (ASA) Physical Status Classification System of I to III.

Exclusion Criteria:

• Patient had a history of allergic reaction or hypersensitivity to any anesthetic agent, narcotic, or benzodiazepine;
• Patient did not meet nils per os (NPO) status per ASA Guideline or institution's guideline.
• Patient had condition(s) that, in the opinion of the Investigator, could interfere with appropriate airway management;
• Patient participated in an investigational drug study within 1 month prior to study start;
• Patient had a history of mental or visual impairment that would not permit successful measurement of cognitive evaluations;
• Patient was unwilling to adhere to pre- and postprocedural instructions; or
• Patient for whom the use of fentanyl or midazolam was contraindicated.

• PPD Development (Study Conduct and Clinical Monitoring)
• Bio Analytical Research Corporation
• MDS Pharma Services
• Coghlan Group (Plasma Sample Supplies)