Guilford Pharmaceuticals Announces Results From AQUAVAN(TM) Injection Bolus Dose Clinical Trial
BALTIMORE, April 18 /PRNewswire-FirstCall/ -- Guilford Pharmaceuticals Inc. (Nasdaq: GLFD - news) announced today that it has completed a Phase I study of AQUAVAN(TM) Injection administered by bolus injection. Preliminary results from the study suggest that rapid bolus administration of AQUAVAN(TM) Injection safely produces loss of consciousness at a similar time as an equipotent infusion of propofol, and produces a longer duration of effect.
AQUAVAN(TM) Injection is a proprietary, patented, water-soluble prodrug of propofol, which is marketed under the tradename DIPRIVAN® Injectable Emulsion. Presently the world's best selling anesthetic, propofol is widely used to induce and maintain anesthesia during surgery, and to sedate patients undergoing certain diagnostic and therapeutic procedures.
``We're very encouraged by these data,'' commented Craig R. Smith, M.D., Chairman and Chief Executive Officer. ``The results from this latest study, together with earlier studies, suggest that AQUAVAN(TM) Injection is a novel, rapid-acting sedative-hypnotic agent with a unique pharmacological profile. We plan to begin a Phase II study of AQUAVAN(TM) Injection in Europe during the second quarter of this year, to further characterize these unique properties and explore the use of AQUAVAN(TM) Injection in a cardiac surgery setting.''
The Phase I study was designed to evaluate the safety, pharmacokinetic and pharmacodynamic properties of propofol derived from AQUAVAN(TM) Injection, compared to DIPRIVAN® Injectable Emulsion. The purpose of the study was to evaluate AQUAVAN(TM) Injection administered as a bolus dose, since a rapid onset of action is desirable in many clinical settings.
In the study, twenty four volunteers were randomized into four cohorts and given a single bolus injection of AQUAVAN(TM) Injection at doses ranging from 5 mg/kg up to 25 mg/kg. One week later, the same subjects received doses of DIPRIVAN® Injectable Emulsion targeted to produce the same peak effect achieved with AQUAVAN(TM) Injection, as measured using a BIS-XP monitor, marketed by ASPECT Medical. DIPRIVAN® Injectable Emulsion was administered at a rate of 50 mg/minute using a computer-controlled infusion pump. Time to loss of consciousness, return of consciousness and duration of unconsciousness were recorded.
In the study, the time to loss of consciousness achieved with AQUAVAN(TM) Injection was comparable to that achieved with DIPRIVAN® Injectable Emulsion. Mean time to LOC was 157 seconds with AQUAVAN(TM) Injection (20 mg/kg), compared to 184 seconds with DIPRIVAN® Injectable Emulsion, and 162 seconds with AQUAVAN(TM) Injection (25 mg/kg) compared to 208 seconds with DIPRIVAN® Injectable Emulsion. With AQUAVAN(TM) Injection, return of consciousness occurred significantly later, and duration of unconsciousness was significantly longer compared to DIPRIVAN® Injectable Emulsion. In the 25 mg/kg dose group, mean time to return of consciousness with AQUAVAN(TM) Injection was 48 minutes compared to 16 minutes with DIPRIVAN® Injectable Emulsion.
Pain on injection occurred in 10 of 24 subjects receiving DIPRIVAN® Injectable Emulsion, and in none of the patients receiving AQUAVAN(TM) Injection. Subjects receiving AQUAVAN(TM) Injection reported a diffuse, unpleasant tingling sensation, which started 60 seconds after administration and was gone within 60 seconds. Similar effects have been reported with other prodrugs. Apnea (cessation of breathing) occurred in 10 of 24 subjects receiving DIPRIVAN® Injectable Emulsion and in 7 of 24 subjects receiving AQUAVAN(TM) Injection.
``I am particularly encouraged with the outcome of this study, which suggests that AQUAVAN(TM) Injection has a very unique pharmacological profile compared to other marketed sedative-hypnotics,'' commented Michel M.R.F. Struys, M.D., Ph.D., Principal Investigator, Department of Anesthesia, Ghent University Hospital, Belgium. ``From these studies, it appears that AQUAVAN(TM) Injection produces stable and predictable levels of anesthesia, and unlike other intravenous sedative-hypnotic agents, with AQUAVAN(TM) Injection, we are able to safely administer enough propofol to produce up to 45 minutes of anesthesia with a single bolus dose injection.''
About AQUAVAN(TM) Injection
AQUAVAN(TM) Injection is a proprietary water-soluble prodrug of propofol in development by Guilford. Unlike DIPRIVAN® Injectable Emulsion, which is propofol formulated in an oil or lipid-based emulsion, AQUAVAN(TM) 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.
Because of its water-soluble formulation and unique properties, Guilford anticipates that AQUAVAN(TM) Injection may minimize or obviate many of the side effects associated with propofol, including: cardiovascular side effects, such as decreased blood pressure, depressed respiration, elevated blood lipid levels, injection site pain, and the potential for bacterial contamination.
Despite some of the associated side effects, propofol is widely used in hospitals and outpatient settings to induce and maintain anesthesia during surgery, or to sedate patients undergoing diagnostic or medical procedures. DIPRIVAN® Injectable Emulsion was launched in the United States in 1989 and is currently the world's leading anesthetic agent. Estimated worldwide sales of propofol in 2001 were approximately $650 million.
Conference Call
Guilford will host a conference call to review the AQUAVAN(TM) Injection Phase I bolus dose results. The conference call will take place at 1:00 p.m. E.T. today, Thursday, April 18, 2002. The dial-in number for participants in the United States and Canada is (888) 675-8007. International callers (706) 679-8253.
Conference Call Replay
An audio replay of the conference call will be available beginning 2 hours after the completion of the call at approximately 3:00 p.m. E.T. today, until approximately midnight on Friday, April 19, 2002. To access the replay, dial 1-800-642-1687, (int'l callers 706-645-9291), then enter conference ID 3876616
Guilford Pharmaceuticals Inc. is a fully integrated pharmaceutical company targeting the neurological, surgical and critical care markets. The Company's mission is to develop proprietary biopolymer-based therapeutics for surgeons and novel pharmaceutical products for the diagnosis and treatment of neurological disorders.
For more information about AQUAVAN(TM) Injection visit www.guilfordpharm.com. |
