Biovail Presents Tramadol Results at American College of Rheumatology.

Business Editors/Health & Medical Writers

TORONTO--(BUSINESS WIRE)--Oct. 28, 2002

-- Biovail's tramadol extended release formulation demonstrated efficacy as early as week one

-- Administration of Biovail's tramadol extended release formulation improved quality of life as exemplified by improved sleep.

-- Tramadol was well tolerated despite an aggressive dose titration schedule.

Biovail Corporation (NYSE,TSE:BVF) presented the results from the Phase III clinical study on tramadol ER (extended release formulation) in treatment of osteoarthritis of the knee at the American College of Rheumatology meeting in New Orleans on Saturday October 26, 2002. Dr. Kenneth Albert, Vice President of Clinical Development, among others, presented this detailed data via a poster presentation. All primary and secondary variable efficacy variables were highly statistically significant and clinically meaningful.

In this study, the primary measure of efficacy was the Arthritis Pain Intensity VAS (visual analog scale) Score from patient visits. The arthritis VAS is a commonly used and validated tool to assess pain intensity and the analgesic potential of a drug product.

Pain was also assessed as a secondary measure of efficacy using the WOMAC Osteoarthritis Index. The WOMAC is a validated, internationally recognized and widely used multidimensional instrument for assessing response to therapy in osteoarthritis. It assesses pain, joint stiffness and physical function, the three major bothersome symptoms in osteoarthritis. In addition, patients and physicians provided a Global assessment of disease and patients recorded their response on a sleep questionnaire as other secondary measures of efficacy.

At the end of the first week of treatment and at all subsequent weeks, tramadol ER was statistically superior to placebo in reducing pain. The magnitude of pain improvement (change from baseline) for the tramadol ER cohort increased weekly throughout the 12 weeks of therapy. By Week 12, patients treated with tramadol ER reported a clinically important 15 mm difference in mean pain relief score compared to placebo. This difference was highly significant (p less than 0.001). The results for the secondary variables as measured by the WOMAC Osteoarthritis scale, paralleled those of the primary with all pain relief results statistically significant in favor of tramadol ER. Additionally, treatment with tramadol ER, compared to placebo, resulted in improved assessments of sleep -- patients had less trouble falling asleep, less awakening by pain during the night or in the morning, and better overall quality of sleep. The average dose of tramadol ER at study end was about 300mg.

Study Design

This was a 12-week, multicenter double blind, randomized, dose-titration, parallel-group comparison of the efficacy and safety of tramadol extended release and placebo in the treatment of osteoarthritis of the knee. Eligible patients with Functional Class I-III osteoarthritis of the knee who reported pain intensity greater than or equal to 40 mm on a visual analog scale (VAS) in the index knee joint were randomly assigned to either tramadol ER or placebo. Two hundred forty-six patients were randomized into the trial.

Patients assigned to tramadol ER were initiated on 100 mg QD and maintained on their dose for at least 3 days after which they were up titrated to 200 mg QD. Further dose escalation and de-escalation was permitted provided that a minimum dose of 200 mg QD was maintained throughout the double-blind treatment phase. Patients randomized to placebo underwent sham dose increases. In patients with pain unresponsive to appropriate dosage adjustments, or with unacceptable side effects, treatment was discontinued and alternate analgesia therapy initiated, as appropriate. Patients returned for efficacy and safety evaluations throughout the 12 weeks of the double-blind treatment phase or at Early Termination.

Tramadol is currently marketed as Ultram by Ortho-McNeil, a division of Johnson and Johnson. Ultram, indicated for the management of moderate to moderately severe pain, may be dosed four to six times per day, and had U.S. sales of $767 million for the 12 months ended June 30, 2002.

Biovail Corporation is an international full-service pharmaceutical company, engaged in the formulation, clinical testing, registration, manufacture, sale and promotion of pharmaceutical products utilizing advanced drug delivery technologies.

For further information, please contact Ken Howling at 905/286-3000 or send inquiries to [e-mail].

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