Insys reports phase 3 trial of Sublingual Buprenorphine spray meets primary endpoint

The trial  was a multicenter, randomized, double-blind, multiple-dose, placebo-controlled study evaluating the efficacy and safety of three dosing regimens of Buprenorphine Sublingual Spray (0.5 mg three times daily (“tid”), 0.25 mg tid, or 0.125 mg tid), and/or matching placebo in subjects with moderate to severe postoperative pain after bunionectomy.  322 subjects were randomized. 

As agreed with the U.S. Food and Drug Administration (“FDA”), the primary efficacy endpoint in this study was the Summed Pain Intensity Difference relative to baseline over a period of 48 hours (SPID-48). 

The patient assessment of pain intensity utilized a numeric pain scale (11-point scale with 0 = no pain to 10 = worst possible pain).

The primary efficacy endpoint was statistically significant at all doses studied.  The Buprenorphine Sublingual Spray 0.5 mg tid demonstrated the largest reduction in SPID-48 and was statistically significant to placebo (p<0.0001).  

The 0.25 mg tid and 0.125 mg tid doses also demonstrated statistically significant reductions in SPID-48 (p = 0.0108 and p = 0.0120, respectively).  All treatments were generally well tolerated. 

Insys Therapeutics chairman, president and CEO John Kapoor said: “We are pleased with the results of this trial indicating that Buprenorphine Sublingual Spray could be a potentially useful drug for the treatment of moderate to severe pain and provide a valuable treatment option in a variety of clinical settings.

"We look forward to discussing these results with the FDA by the end of the year and subsequent next steps towards filing a New Drug Application."

About Pharmaceutical Buprenorphine

Insys is developing Buprenorphine Sublingual Spray for sublingual administration as a treatment for moderate to severe pain. The active ingredient is buprenorphine, which is a partial opioid agonist at the mu-opioid receptor and antagonist at the kappa-opioid receptor. Buprenorphine binds to mu-receptors with high affinity but less intrinsic activity compared to full opioid agonists.

Because of its partial agonist features, the efficacy and adverse effects of buprenorphine are thought to plateau at higher doses.  Further, buprenorphine dissociates from the mu-receptor very slowly, which likely accounts for its longer duration of action than morphine, and its low level of manifested physical dependence. Actions at kappa-receptors, where buprenorphine is an antagonist, are believed to produce alterations in the perception of pain and the emotional response to pain.

About Moderate to Severe Pain

Millions suffer from acute pain every year and the effects of pain is typically experienced when the free nerve endings of pain receptors are subject to noxious mechanical, thermal, or chemical stimuli. These pain receptors can transmit signals along afferent neurons to the spinal cord and then to the brain.

When a person feels pain, any one or more of a number of problems can be associated with this sensation including, but not limited to, reduced function, reduced mobility, complication of sleep patterns, and decreased quality of life. The effects of pain exact a tremendous costs, in rehabilitation, lost worker productivity, as well as the emotional and financial burden it places on patients and their families.