A Study of AQUAVAN® Injection in the Presence of Pre-Medication in Patients Undergoing Minor Surgical Procedures

A Phase III, Randomized, Open-label Study to Assess the Safety and Efficacy of AQUAVAN® Injection Versus Midazolam HCl for Sedation in Patients Undergoing Minor Surgical Procedures

The purpose of this study is to determine the safety, tolerability, and efficacy of AQUAVAN® Injection when used for mild-to-moderate sedation in patients undergoing minor surgical procedures.

Randomized, open label, multi-center,midazolam adaptive dose ranging study, in which several dose levels of AQUAVAN® Injection and fentanyl citrate injection will be investigated to produce a desired sedation level in patients undergoing minor surgical and/or therapeutic procedures. A desired sedative dose/dose range and dosing paradigm will be identified based on pre-set criteria using the Modified Observer's Assessment of Alertness/Sedation (OAA/S). The desired sedative dose/dose range and dosing paradigm of AQUAVAN® Injection is defined as one that consistently provides mild to moderate sedation (Modified OAA/S between 2 and 4 inclusive) in majority of patients who are pre-medicated with fentanyl citrate injection.

Midazolam is the most widely used i.v. agent for minimal-to-moderate sedation. The dose range of midazolam to induce minimal to moderate sedation was based on standard clinical practice.

[new paragraph] All patients were pre-medicated with fentanyl citrate as an analgesic.

The outpatient setting has become increasingly popular for various types of medical procedures requiring sedation. In outpatient minor surgical procedures, sedation agents are used to provide mild-to-moderate sedation and are used with other medicines for pain management. Surgeons have searched for alternative treatments to use in the outpatient setting that would provide a faster recovery time with minimal post-procedure amnesia. This injection is used following pretreatment with fentanyl citrate for pain management.

Inclusion Criteria:

1. Patient provided signed/dated Informed Consent and HIPAA Authorization after receiving a full explanation of the extent and nature of the study.
2. Patient was at least 18 years of age at the time of screening. (Prior to Amendment 1, dated 03 February 2005, this criterion restricted enrollment to patients who were ≥18 and ≤65 years of age. To ensure that safe dosing levels were administered to patients >65 years of age, AQUAVAN and midazolam dosing levels were reduced when compared with patients between 18 and 65 years of age, inclusive. The majority of patients were enrolled prior to 03 February 2005.)
3. Female patient must have been surgically sterile, postmenopausal, or not pregnant or lactating, and must have been 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 predosing periods.
4. Patient met the American Society of Anesthesiologists (ASA) Physical Status Classification System of I to III.
5. Patient may have been an inpatient or outpatient scheduled to undergo a single minor surgical and/or therapeutic procedure.

Exclusion Criteria:

1. Patient had a history of allergic reaction or hypersensitivity to any anesthetic agent, narcotic, or benzodiazepine.
2. Patient did not meet nils per os (NPO) status per ASA Guideline or institution's guideline.
3. Patient had condition(s) that, in the opinion of the Investigator, could interfere with appropriate airway management.
4. Patient had participated in an investigational drug study within 1 month prior to study start.
5. Patient had a history of mental or visual impairment that would not permit successful measurement of cognitive evaluations.
6. Patient was unwilling to adhere to pre- and postprocedural instructions.
7. The use of fentanyl or midazolam was contraindicated for the patient.
8. Patient had experienced multiple concurrent injuries or trauma.
9. Patient was scheduled to undergo multiple same-day procedures (eg, bunionectomies on both feet).