Biovail Reports Second Positive Phase III Clinical Result for Tramadol Extended Release Formulation.

Business Editors/Health & Medical Writers

TORONTO--(BW HealthWire)--Jan. 14, 2002

Biovail Corporation (NYSE:BVF)(TSE:BVF)

-- Biovail's extended release tramadol formulation demonstrated

statistically significant and clinically meaningful dose

related reductions in pain compared to placebo in low back

pain

-- Results parallel Biovail's positive Phase III clinical results

on the use of extended release tramadol in chronic pain

associated with osteoarthritis 

Biovail Corporation (NYSE, TSE:BVF) today announced significant Phase III clinical results of its extended release formulation of tramadol. Tramadol is currently dosed 3 to 4 times per day and is prescribed for the treatment of moderate to moderately severe pain. The multi-dose tramadol formulation is currently sold under the brand name Ultram by a division of Johnson and Johnson. Sales of Ultram for the twelve months ended September 2001 grew by approximately 16.5% and were in excess of $620 million.

In the recently completed study, Biovail's extended release (ER) tramadol formulation produced statistically significant and clinically meaningful dose-related reductions in chronic low back pain compared to placebo following a 12-week randomized, placebo controlled, double blind treatment phase in which patients were randomized to receive tramadol ER doses of either 300mg or 200mg or placebo. The primary efficacy variable was pain intensity since the previous visit as measured on a Visual Analog Scale (VAS). Secondary measures of efficacy were the patient's current pain intensity, the patient's global evaluation of the study medication, the Roland Disability Index, the patient's assessment of sleep and premature study termination due to lack of efficacy.

As early as week 1, the first time point evaluated, Biovail's extended release tramadol formulation was statistically superior to placebo in reducing pain and ER tramadol 300mg was more effective than the 200mg dose. The effects of ER tramadol were sustained over the 12- week study duration. The results for the secondary variables paralleled those of the primary outcome variables.

Dr. Thomas J. Schnitzer, who is Director, Office of Clinical Research at Northwestern University Medical School, commented, "The results of this trial provide significant support for the efficacy and safety of extended release tramadol in patients with chronic low back pain. For chronic conditions such as osteoarthritis and low back pain, the availability of an effective longer-acting formulation of tramadol provides practitioners and patients with a therapeutic alternative that may be more convenient to prescribe and use. Indeed, this extended release formulation has previously demonstrated significant pain relieve in a Phase III clinical trial involving patients with osteoarthritis of the knee."

Overall Study Design and Plan

The clinical trial was designed to evaluate the efficacy and safety of Biovail's extended release tramadol (once-daily) formulation in the treatment of chronic low back pain. The study included an open label run-in phase to identify patients for continuation in the double blind phase who tolerated tramadol and perceived a benefit.

Patients between the ages of 18 and 80 years with a history of chronic lower back pain of at least 6 months and requiring daily medication for at least 2 of 3 months and otherwise in good health were eligible for enrollment. Patients who met the inclusion and exclusion criteria at screening entered a 2 to 7 day washout period during which all analgesic use was discontinued. Eligible patients who reported a pain intensity of greater than or equal to 40 mm on a visual analog scale (VAS) entered a 3-week, open label run-in period.

During the 3-week run-in period, patients were initiated on 100mg QD and maintained on their dose for at least 3 days. On Day 4 and for the remainder of the first week, patients were permitted to have their dose increased to 200 mg QD based upon the tolerability of side effects. Beginning the second week, patients were maintained on a minimum of 200 mg QD and the dose titrated upward to 300 mg QD based upon the tolerability of side effects. Beginning the third week, patients were escalated to a dose of 300 mg QD and maintained at that dose for 1 week. No further dose adjustments were permitted during the remainder of the run-in period. Patients with pain unresponsive to appropriate dosage adjustments or with unacceptable side effects were dropped from the study. Eligible patients receiving Tramadol ER 300 mg at the end of the 3-week run-in period entered the 12-week double blind randomized phase of the study.

At the start of the double blind treatment phase, approximately 380 eligible patients were randomly assigned to receive Tramadol ER 300 mg QD, Tramadol ER 200 mg QD or placebo QD. Patients returned for efficacy and safety evaluations at Weeks 1, 2, 4, 8 and 12 of the double blind phase or at Early Termination.

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.

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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 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.