Efficacy and safety evaluated in opioid-naïve 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, placebo-controlled trial of opioid-naïve patients with moderate to severe chronic low back pain

Patients were suboptimally responsive to their non-opioid pain medications

Patients were considered "opioid-naïve" if treated with non-opioids only—OR if treated with less than 5 mg of oxycodone (or equivalent) per day in the 3 months before screening and who, in the opinion of the investigator, were not physically dependent on an opioid¹

• In the open-label, dose-titration period
• Patients who entered into the study (N=1024) had chronic low back pain and were suboptimally responsive to their non-opioid therapy
• 23% of patients discontinued due to an adverse event, 14% due to lack of therapeutic effect, and 10% for various administrative reasons
• 53% of patients who entered the open-label titration period (n=539) were able to titrate to a tolerable and effective dose 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 10 or 20 mcg/hour were then randomized to remain on their titrated dose of Butrans or matching placebo
• 66% (170) of patients treated with Butrans completed the 12-week treatment compared with 70% (199) of patients treated with placebo¹
• Of patients randomized to Butrans (n=256), 9% discontinued due to lack of efficacy, and 16% due to adverse events
• Of patients randomized to placebo (n=283), 13% discontinued due to lack of efficacy, and 7% due to adverse events
• During the first 7 days of the double-blind treatment period, patients were allowed up to 2 tablets/day of immediate-release oxycodone 5 mg as supplemental analgesia to minimize opioid withdrawal symptoms in patients randomized to placebo. Thereafter, supplemental analgesia was limited to either acetaminophen 500 mg or ibuprofen 200 mg at a maximum of 4 tablets/day
• Of the patients who were able to be randomized, the mean pain (SE) Numerical Rating Scale (NRS) scores were 7.2 (0.08) and 7.2 (0.07) at screening and 2.6 (0.08) and 2.6 (0.07) at pre-randomization (beginning of double-blind period) for the Butrans and placebo groups, respectively

Butrans demonstrated improvement in pain scores in opioid-naïve 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 vs placebo

• Primary efficacy endpoint score for average pain over the last 24 hours* at the end of the study (Week 12/Early Termination) was statistically significantly lower for patients treated with Butrans 10 mcg/hour or 20 mcg/hour (n=256) compared with patients treated with placebo (n=283)¹

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

53% of patients treated with Butrans achieved at least a 30% improvement in pain score from screening to study endpoint, as shown below.¹

46% of patients treated with placebo achieved at least a 30% improvement in pain score from screening to study endpoint, as shown below.¹