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Axcan's High Dose Safety Study on ITAX in Healthy Subjects Shows No Cardiac Adverse Drug Reaction - Results of a large, high dose, electrocardiogram trial completed in 162 healthy subjects

Dec 15, 2004 - 12:00 ET

MONT SAINT-HILAIRE, Quebec, Dec. 15 - Axcan will host a conference call Wednesday, Dec. 15, at 9:00 A.M. E.T.

Axcan Pharma Inc. ("Axcan" or the "Company") announced positive cardiac safety results of a high
dose (supratherapeutic) study for the new prokinetic agent, ITAX™ (Itopride
hydrochloride). In this study, ITAX had no clinically relevant effects on
heart rate, cardiac conduction and cardiac repolarization.
    "We are extremely pleased that this important safety study has indicated
that Itopride (ITAX) tablets, even at four times the intended therapeutic
dose, have shown no toxic effects on the heart," said Léon F. Gosselin,
President and Chief Executive Officer of Axcan. "After having achieved this
important milestone, we can now fully focus on executing the Phase III
clinical trial program to demonstrate its safety and effectiveness in treating
functional dyspepsia."


    The Electrocardiogram ("ECG") trial was intended to determine the
cardiotoxicity potential of Itopride. The study used a single-site,
randomized, placebo and positive controlled, parallel designed, steady state
(5 days), multiple dose trial. The study involved 162 healthy male and female
volunteers aged 18-45 years. Itopride at 100 mg three-times-a-day and at a
supratherapeutic dose of 400 mg three-times-a-day was compared to placebo and
moxifloxacin, an antibiotic that produces a 5-10 ms effect on cardiac
repolarization as defined by changes in the individually corrected QT interval
    An expert centralized ECG laboratory analyzed more than 13,000 digital
ECGs using a high-resolution manual on-screen caliper method with annotations.
All subjects received placebo on day 1 in a single-blind fashion. ECGs were
recorded using a digital continuous 12-lead (H-12) system over 24 hours at
baseline and steady state.
    The study as conducted, confirmed an expected 8 ms placebo-corrected QTc
prolongation in the moxifloxacin group Conversely, Itopride, at clinical and
supratherapeutic doses showed a 1 and 2 ms placebo corrected change and 2 and
3 ms using the maximum QTcI duration derived by taking the longest interval at
any time point in each subject. Therefore, the variation in QTc for the
Itopride groups was well within the 5 ms safety margin considered by experts
as having no impact on cardiac safety. (Draft Guidelines on Clinical
Evaluation of QT interval prolongation -2002- FDA web-site). Thus, there were
no clinically relevant effects of Itopride on heart rate, cardiac conduction
(PR and QRS duration) or cardiac repolarization (QTcI). In light of these
results in healthy volunteers, Itopride does not appear to affect the QTc
    "These results suggest that this new prokinetic agent should have no
cardiac safety issues related to QTc; indeed, drugs whose maximum effect on
QTc interval duration is less than 5 ms at high doses have not so far been
associated with 'torsades de pointe' (TDP)," says Dr. Morganroth, a well known
cardiologist of the University of Pennsylvania and eResearch Technology, both
in Philadelphia.


    ITAX is a patented oral gastroprokinetic drug with antiemetic properties
for the treatment of gastrointestinal symptoms caused by reduced
gastrointestinal motility. Axcan licensed ITAX from Abbott Laboratories in
September 2003. Phase III clinical studies for ITAX are underway in North
America and Europe and involve approximately 1000 patients. These Phase III
clinical studies are testing ITAX in the treatment of functional dyspepsia,
the first indication pursued by the Company.
    Itopride Hydrochloride has been marketed in Japan since 1995.


    Functional dyspepsia, a disorder of the upper gastrointestinal system,
affects up to 25% of the US population annually and accounts for up to 5% of
all visits to primary care physicians (Talley et al Gastroenterology
1992:102;1259-1268). Currently, there are no known approved drugs for this
indication in the United States.

    Axcan will host a conference call at 9:00 A.M., on December 15, 2004.
    Interested parties may also access the conference call by way of web cast
    at . The web cast will be archived for 90 days. The
    telephone numbers to access the conference call are (800) 814-4862
    (Canada and United States) or (416) 640-1907 (international). A replay of
    the call will be available until December 22, 2004. The telephone number
    to access the replay of the call is (416) 640-1917 code: 21105448.


    Axcan is a leading specialty pharmaceutical company involved in the field
of gastroenterology. The Company markets a broad line of prescription products
sold for the treatment of symptoms in a number of gastrointestinal diseases
and disorders such as inflammatory bowel disease, irritable bowel syndrome,
cholestatic liver diseases and complications related to cystic fibrosis.
Axcan's products are marketed by its own sales force in North America and
Western Europe. Its common shares are listed on the Toronto Stock Exchange
under the symbol "AXP" and on the NASDAQ National Market under the symbol

    "Safe Harbor" statement under the Private Securities Litigation Reform
    Act of 1995.

    To the extent any statements made in this release contain information
    that is not historical, these statements are essentially forward looking
    and are subject to risks and uncertainties, including the difficulty of
    predicting FDA and other regulatory approvals, acceptance and demand for
    new pharmaceutical products, the impact of competitive products and
    pricing, new product development and launch, reliance on key strategic
    alliances, availability of raw materials, the regulatory environment,
    fluctuations in operating results and other risks detailed from time to
    time in the Company's filings with the Securities and Exchange Commission
    and the Canadian Multijurisdictional Disclosure System.

    ITAX is a trademark of Axcan or its affiliates.

David W. Mims, Executive Vice President and Chief Operating Officer, Axcan Pharma Inc., (205) 991-8085 ext. 3223, Julie M. Thibodeau, Manager, Investor Relations, Axcan Pharma Inc., (450) 467-2600 ext. 2062,