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Study: Aquavan Provides Rapid Onset, Recovery From Procedural Sedation in Colonoscopy
The confirmatory Phase II clinical trial was an open label, multi-center study of a fixed dose regimen of AQUAVAN® to provide procedural sedation in patients undergoing elective colonoscopy. The study enrolled healthy adults aged 20 to 85 who were pre-treated with fentanyl citrate, an analgesic commonly used for pain relief during brief diagnostic procedures. Five minutes after receiving fentanyl, patients were given an intravenous bolus dose of AQUAVAN®. AQUAVAN® was administered by medical personnel as dictated by local hospital guidelines; administration by an anesthesiologist was not required.
Phase II Trial Background
In the first dose-ranging Phase II trial, a total of 91 patients were evaluated. Drug dosing was based on an individual's weight and consisted of three dose groups of AQUAVAN® (7.5, 10, and 12.5 mg/kg) and three dose groups of fentanyl (0.5, 1.0, and 1.5 ug/kg), resulting in a total of nine AQUAVAN®/fentanyl dose-combinations. The purpose of the dose-ranging study was to identify the optimal dosing combination of AQUAVAN® and fentanyl for evaluation in a confirmatory study.
Confirmatory Trial Design
The confirmatory Phase II study enrolled a total of 64 patients undergoing elective colonoscopy. Patients were dosed according to a pre-defined fixed-dose regimen.
Sedation was measured using the Modified Observer's Assessment of Alertness/Sedation (OAA/S) scale. The desired sedative effect was defined as one that consistently provided procedural sedation, or a Modified OAA/S score of between 1 and 4. Patients were continuously monitored for adverse events and vital signs throughout the study. Measurements of safety, tolerability and patient and physician satisfaction were also assessed.
Confirmatory Phase II Trial Results
Following bolus administration of AQUAVAN®, the median time to achieve sedation was two minutes. The median time to full alertness after removal of the colonoscope was twelve minutes, and the median time to full recovery, defined as the ability to stand without instability or assistance, was twenty minutes. Gastroenterologists rated 94% of patients as adequately sedated by AQUAVAN® for the duration of the procedure.
The most common adverse event experienced in the study was a transitory itching or tingling sensation, often called paresthesias, reported by 89% of patients in the confirmatory study. Of the patients reporting paresthesias, 73% rated the event as mild to moderate discomfort. The paresthesias were not considered a serious adverse event, and did not affect the patients' acceptance of or satisfaction with the drug. Brief episodes of apnea, defined as lack of spontaneous breathing for more than 15 seconds, were reported in 5% of patients and were successfully resolved without medical intervention. No patients required respiratory support or endotracheal intubation. There was no pain at the injection site reported. There were three episodes of mild, transient hypotension, all of which were successfully treated with a short course of fluids or ephedrine.
Following the procedure, the majority of patients and physicians reported a high level of satisfaction with AQUAVAN®. In the confirmatory study, 94% of patients responding indicated they would use the drug again. On a scale of 0 to 100 (100 representing highly satisfied and 0 representing dissatisfied), 74% of patients rated their experience better than 90. Gastroenterologists rated 100% of the patients' experiences as good to excellent.
In the confirmatory study, most patients were adequately sedated with a single bolus dose for the duration of the procedure. Patients recovered quickly after the procedure, had a feeling of mild euphoria and left the endoscopy suite alert, and able to follow post-operative instructions.
Dr. Ron Pruitt, President and Medical Director, Nashville Medical Research Institute, Chairman of Gastroenterology, Saint Thomas Hospital, Nashville, Tennessee and an investigator in the study, commented, "The most recent results confirm the findings from an earlier Phase II study combining AQUAVAN® and fentanyl citrate. AQUAVAN® has shown a distinctly favorable profile for use in procedural sedation. The fact that we have seen strong patient satisfaction is particularly relevant when we realize that these patients are considering an elective procedure. I believe that the use of AQUAVAN® could increase patient acceptance of elective colonoscopy, ultimately contributing to patient welfare."
Craig Smith, M.D., Chairman, President and Chief Executive Officer of Guilford, remarked, "Our registration strategy for AQUAVAN® will involve four pivotal Phase III trials, as well as several smaller supportive studies. A total of 900 patients will be enrolled in the Phase III program for AQUAVAN®. The goal of this broad clinical program is to allow us to seek registration for AQUAVAN® Injection for an indication in procedural sedation during brief diagnostic and therapeutic procedures such as colonoscopy, bronchoscopy, interventional cardiology and minor surgical and therapeutic procedures."
About AQUAVAN® Injection
AQUAVAN® is a proprietary water-soluble prodrug of propofol exclusively licensed by Guilford from ProQuest Pharmaceuticals. Unlike propofol, which is formulated in an oil or lipid-based emulsion, AQUAVAN® is formulated as a clear aqueous solution and the prodrug is rapidly converted by an enzyme in the body called alkaline phosphatase into propofol after intravenous injection.
Because of its water-soluble formulation and unique pharmacological properties, Guilford anticipates that AQUAVAN® may overcome many of the limitations and side effects associated with current sedatives and anesthetics.
Source: Guilford Pharmaceuticals Inc.