Efficacy and safety evaluated in opioid-experienced patients

Clinical studies

The efficacy of Butrans has been evaluated in four 12-week, double-blind, controlled clinical trials in opioid-naïve and opioid-experienced patients with moderate to severe chronic low back pain or osteoarthritis using pain scores as the primary efficacy variable. Two of these studies demonstrated efficacy in patients with low back pain. One study in low back pain and one study in osteoarthritis did not show a statistically significant pain reduction for either Butrans or the respective active comparators.

Efficacy and safety of Butrans was evaluated in a 12-week, double-blind, trial of opioid-experienced patients with moderate to severe chronic low back pain

• Required prior therapy¹
• 30 to 80 mg/day of oral morphine sulfate or opioid equivalent, for at least 4 days a week, for at least 30 days prior to screening¹
• The most commonly observed opioid medications used by subjects entering the study were hydrocodone medications (62%), followed by oxycodone medications (21%) and propoxyphene medications (12%). Patients were required to discontinue their current opioid analgesic regimen
• Exclusion criteria included¹
• Patients using fentanyl transdermal system or extended-release hydromorphone for pain control
• Subjects taking more than 80 mg/day of oral morphine sulfate or equivalent within 30 days of screening
• Patients requiring frequent analgesic therapy for other chronic conditions

• In the open-label, dose-titration period
• Patients entered into the study (N=1160) were on chronic opioid therapy, with a total daily dose of 30 to 80 mg morphine equivalent
• 21% of patients discontinued due to lack of therapeutic effect, and 12% due to an adverse event
• 57% of patients who entered the open-label titration period (n=662) were able to titrate to and tolerate the adverse effects of Butrans 20 mcg/hour and were randomized into a 12-week double-blind treatment period¹
• In the double-blind period
• Patients who achieved adequate analgesia and tolerable adverse effects on Butrans 20 mcg/hour were then randomized to remain on Butrans 20 mcg/hour or were switched to a low-dose control of Butrans 5 mcg/hour or an active control
• 67% (146) of patients treated with Butrans 20 mcg/hour and 58% (128) of patients treated with Butrans 5 mcg/hour completed the 12-week treatment¹
• Of patients randomized to Butrans 5 mcg/hour (n=221), 24% discontinued due to lack of efficacy, and 6% due to adverse events
• Of patients randomized to Butrans 20 mcg/hour (n=219), 11% discontinued due to lack of efficacy, and 13% due to adverse events
• During the double-blind period, patients were permitted to take ibuprofen (200 mg tablets) or acetaminophen (500 mg tablets) every 4 hours as needed for supplemental analgesia (up to 3200 mg of ibuprofen and 4 grams of acetaminophen daily)
• Of the patients who were able to be randomized in the double-blind period, the mean pain (SE) Numerical Rating Scale (NRS) scores were 6.4 (0.08) and 6.5 (0.08) at screening and 2.8 (0.08) and 2.9 (0.08) at pre-randomization (beginning of double-blind period) for the Butrans 5 mcg/hour and Butrans 20 mcg/hour treatment groups, respectively

Butrans 20 mcg/hour demonstrated improvement in pain scores in opioid-experienced patients

Study results

Statistically significantly lower score for average pain over the last 24 hours at Week 12 for patients with moderate to severe chronic low back pain treated with Butrans 20 mcg/hour vs Butrans 5 mcg/hour

• Primary efficacy endpoint score for average pain over the last 24 hours* at the end of the study (Week 12) was statistically significantly lower for patients treated with Butrans 20 mcg/hour (n=219) compared with patients treated with Butrans 5 mcg/hour (n=221)¹

*Based on an 11-point scale where 0=no pain and 10=pain as bad as you can imagine.¹

49% of patients randomized to Butrans 20 mcg/hour achieved at least a 30% improvement in pain score from screening to study endpoint, as shown below.

33% of patients randomized to Butrans 5 mcg/hour achieved at least a 30% improvement in pain score from screening to study endpoint, as shown below.