Purdue Pharma L.P. Presents Phase 3 Study of Transdermal Delivery of Buprenorphine in Moderate to Severe Pain

Purdue Pharma L.P. Presents Phase 3 Study of Transdermal Delivery of Buprenorphine in Moderate to Severe Pain

San Diego, CA – May 7, 2009 – The investigational opioid analgesic buprenorphine 20 mcg/h transdermal system (BTDS 20) significantly reduced "average pain over the last 24 hours" scores when used in subjects with moderate to severe pain, according to results of a Phase 3 study presented today at the 28th annual scientific meeting of the American Pain Society in San Diego.

Buprenorphine is approved for use in the United States for the relief of moderate to severe pain and can be administered either intravenously or intramuscularly. It is also available in this country in sublingual formulations for the treatment of opioid dependency.

In the U.S., BTDS is in Phase 3 development by Purdue Pharma L.P. for the treatment of moderate to severe pain in patients requiring continuous, around-the-clock treatment with opioid medications. BTDS is currently marketed for the treatment of moderate to severe pain in more than 10 countries outside of the US, including the UK and Germany.

Summary of Efficacy and Safety Data
In this randomized, double-blind, double-dummy study, analysis of the primary efficacy endpoint, "average pain over the last 24 hours" scores, showed that subjects treated with BTDS 20 (buprenorphine, 20 mcg/h) experienced significant decrease in pain scores compared to those treated with BTDS 5 (buprenorphine, 5 mcg/h) [P <.001]. Subjects were assessed at weeks 4, 8 and 12, using a repeated measures analysis.

An immediate-release oxycodone (OxyIR®, 40 mg/day) arm was included to assess assay sensitivity. OxyIR® was associated with a statistically significant decrease in "average pain over the last 24 hours" scores compared to BTDS 5 (P <.001), demonstrating the sensitivity and validity of the study design and choice of reference treatment used to evaluate pain in this study.

The results of 4 sensitivity analyses, performed to assess the robustness of the primary efficacy analysis with respect to differing imputation algorithms, were all statistically significant for BTDS 20 compared to BTDS 5 (P < .001) and consistent with the results of the primary efficacy analysis. There were statistically significant differences observed between the OxyIR® and BTDS 5 treatment groups for all sensitivity analyses (P < .001).

Responder analyses revealed that the numbers of subjects treated with BTDS 20 and OxyIR® reporting 30 percent and 50 percent improvement from baseline screening in "average pain over the last 24 hours" were significantly higher compared to those treated with BTDS 5. The treatment related adverse events during this study and for the 3 treatment groups were primarily classified as gastrointestinal, nervous system, and skin reactions at the administration site. The adverse events most frequently observed during the double-blind phase for subjects treated with BTDS 5, BTDS 20, and OxyIR®, respectively, were nausea (8%, 12%, and 8%) application site pruritus (itching) [5%, 13%, and 9%], application site erythema (5%, 10%, and 9%), application site rash (8%, 9%, and 6%) and headache (5%, 11%, and 8%).

The incidence of adverse events observed for BTDS 20 and OxyIR® were comparable, both in terms of the types of events and the most frequently reported events.

Robust Study Design
Subjects evaluated in this study had moderate to severe low back pain for at least 3 months and were receiving treatment with opioid analgesics at doses between 30 to 80 mg of morphine sulfate or the equivalent at least 4 days per week for at least 30 days prior to the first visit. 62% of subjects were taking hydrocodone, 21% were taking oxycodone (either alone or in combination with non-opioids) and 12% of subjects were taking propoxyphene-containing medications. Prospective subjects were excluded if they were currently using the fentanyl transdermal-system or more than 80 mg per day of oral morphine equivalent for pain control upon entry into the study.

The study employed an enriched design, allowing only subjects who both tolerated and responded to BTDS during an open label run-in period to enter into the 12-week double-blind phase of the trial, mimicking the treatment of patients with moderate to severe pain in a clinical practice setting. The efficacy of BTDS 20 was assessed using BTDS 5. All subjects wore either active or placebo patches (double-dummy technique, i.e., subjects in the OxyIR® treatment group wore placebo transdermal systems).

The study was conducted in 75 U.S. research sites with a broad representation of the many medical specialties involved in the treatment of pain (e.g., orthopedists, orthopedic surgeons, rheumatologists, pain management specialists, anesthesiologists and general practitioners).

During the double-blind phase, a total of 660 subjects were randomized to and received BTDS 5, BTDS 20 or OxyIR® 40 mg (10 mg QID) for 12 weeks.

Buprenorphine Transdermal System Technology
The investigational buprenorphine transdermal system evaluated in this study employs a matrix design, in which the active drug is contained within the adhesive matrix layer, allowing for a thin profile which is not visible under clothing. Some transdermal products have a reservoir design, with medication contained within a "jelly bag". BTDS is not a reservoir design. All BTDS doses under investigation are supplied in patches which are equally thin but have different surface dimensions.

After application, plasma buprenorphine concentrations steadily increase within the first 24 to 48 hours and reach steady-state within approximately 72 hours. BTDS delivers a consistent dose of buprenorphine with limited fluctuation over a seven-day period; peak concentration is sustained with repeat dosing.

OxyIR® (oxycodone immediate release oxycodone) Capsules are indicated for the relief of moderate to moderately severe pain.

OxyIR® Capsules are contraindicated in patients with known hypersensitivity to oxycodone, or in any situation where opioids are contraindicated. This includes patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe bronchial asthma or hypercarbia. OxyIR® Capsules are contraindicated in any patient who has or is suspected of having paralytic ileus.

Oxycodone products are common targets for both drug abusers and drug addicts.

Respiratory depression is the chief hazard from all opioid agonist preparations. Respiratory depression occurs most frequently in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration.

The most frequently observed reactions listed in the OxyIR® prescribing information include lightheadedness, dizziness, sedation, nausea, and vomiting.

Please view the prescribing information at http://www.pharma.com/PI/Prescription/OxyIR.pdf.

About Purdue Pharma L.P.
Purdue Pharma L.P. and its associated U.S. companies are privately-held pharmaceutical companies known for pioneering research on acute, chronic and persistent pain. With corporate and medical research headquarters in Stamford, CT, Purdue Pharma L.P. is engaged in the research, development, production, and distribution of both prescription and over-the-counter medicines and hospital products. Additional information about Purdue Pharma L.P. can be found at www.purduepharma.com.

Note to Editors:
The Efficacy and Safety of Buprenorphine Transdermal System (BTDS) in Subjects With Moderate to Severe Low Back Pain: A Double-blind Study (poster #305) will be posted during scheduled poster and exhibit hours in the Exhibit Hall on Thursday, May 7; and presented from 4:15 to 5:45 PM (PDT).

For Immediate Release