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Phase 3 Trials of Aquavan Injection Begin

BALTIMORE, Sept. 20 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals Inc. (NASDAQ:GLFD) today announced the initiation of a Phase III, randomized, open-label, blinded-evaluator study to assess the safety and overall efficacy of AQUAVAN(R) Injection versus midazolam HCl for sedation in patients undergoing colonoscopy procedures. The trial will enroll up to 267 patients at approximately 30 sites throughout the United States. This is the first of several Phase III studies Guilford expects to commence in its AQUAVAN(R) development program.

Craig R. Smith, M.D., Guilford's President and Chief Executive Officer, remarked, "We expect to seek approval for AQUAVAN(R) for procedural sedation for brief diagnostic and therapeutic procedures such as colonoscopy, bronchoscopy, interventional cardiology, and minor surgical and therapeutic procedures. This is a large and growing market opportunity; already more than 50 million brief diagnostic and therapeutic procedures requiring sedation occur each year in the United States. This number is expected to increase as the population ages and advancements in medical technology continue to shift a greater number of procedures into the outpatient setting. Our current development program for AQUAVAN(R) includes several Phase III clinical trials. Results from some of these studies are expected to be available beginning in the first half of next year."

Ron Pruitt, M.D., President and Medical Director, Nashville Medical Research Institute, Chairman of Gastroenterology, Saint Thomas Hospital, Nashville, Tennessee and an investigator in the study, commented, "Previous results with AQUAVAN(R) suggest that it has an ideal profile for use in providing procedural sedation in patients undergoing elective procedures such as colonoscopy. I have been very impressed that patients receiving AQUAVAN(R) have been able to leave the endoscopy suite clear-headed and able to follow post-operative instructions. Patient satisfaction is particularly relevant in an elective procedure and could strongly influence patient acceptance and physician adoption of AQUAVAN(R)."

Phase III Trial Design
The first Phase III trial will assess the safety and overall efficacy of AQUAVAN(R) versus midazolam HCl following pretreatment with the analgesic agent, fentanyl citrate injection. Patients aged 18-65 undergoing elective colonoscopy will be enrolled and randomly assigned to receive either midazolam HCl or AQUAVAN(R) according to a pre-defined fixed-dose regimen.

Sedation will be measured using the Modified Observer's Assessment of Alertness/Sedation (Modified OAA/S) scale. The primary efficacy endpoint in the trial is success of sedation, defined as: three consecutive Modified OAA/S scores less than or equal to 4, and completing the procedure without employing alternative sedative medications and without requiring manual or mechanical ventilation. Secondary efficacy endpoints include: duration of sedation; time to recovery and fully alert following the procedure; and patients' and physicians' ratings of the procedure.

To avoid observer bias, an individual who is blinded to the treatment assignments (AQUAVAN(R) or midazolam HCl) will administer the pre- and post- sedation cognitive assessments; sedation assessment (OAA/S) and patient satisfaction surveys. Patients will be continuously monitored for adverse events and vital signs throughout the study.

Previous Phase II Findings
Results from Guilford's confirmatory fixed-dose, open-label, multi-center Phase II study of AQUAVAN(R) in combination with fentanyl citrate suggest that AQUAVAN(R) provides rapid onset and rapid recovery from procedural sedation in a convenient dosing regimen and without significant adverse events in patients undergoing colonoscopy. The majority of patients and physicians reported a high level of satisfaction with AQUAVAN(R), with over 90% of patients responding indicating they would use the drug again. Patients also recovered quickly after the procedure and left the endoscopy suite alert and able to follow post-operative instructions.

The most common adverse event experienced in the Phase II study was a transitory itching or tingling sensation, often called paresthesias. Of the patients reporting paresthesias, over 70% rated the event as mild to moderate discomfort. The paresthesias were not considered a significant adverse event, and did not affect patients' acceptance of or satisfaction with the drug. Brief episodes of apnea, defined as a lack of spontaneous breathing for at least 15 seconds, were reported in 5% of patients and successfully resolved without medical intervention. No patients required respiratory support or endotracheal intubation. There was no pain at the injection site reported, and 1.8% of patients experienced transient hypotension that was self- resolving.

About AQUAVAN(R) Injection
AQUAVAN(R) Injection 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(R) Injection is formulated in a clear aqueous solution and is rapidly converted by an enzyme in the body called alkaline phosphatase into propofol after intravenous injection.

Source: Guilford Pharmaceuticals Inc.

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