Abstract Title: A Phase 2 Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Clinical Efficacy, Safety, and Tolerability of the Sublingual Sufentanil NanoTab in the Treatment of Breakthrough Pain in Cancer Patients
Srinivas R Nalamachu, MD, Overland Park, KS
Richard L Rauck, MD, Winston-Salem, NC; Pamela P Palmer, MD, PhD, Redwood City, CA
Abstract Type: Clinical Investigation
Introduction: Currently, oral transmucosal fentanyl products are the only FDA-approved drugs specifically for the treatment of cancer breakthrough pain (CBTP). While these products all have a relatively rapid onset of analgesia compared to traditional oral/gastrointestinal opioids, they display a wide range of peak plasma concentrations (Tmax ranges up to 240 minutes for all approved products) and a wide range of half-lives (T1/2 ranges to well above 10 hours). Since the duration of a CBTP event ranges from 15 – 60 minutes, the erratic and prolonged pharmacokinetics of oral transmucosal fentanyl is not optimal and can result in excess opioid exposure for a short-duration pain event. Furthermore, there are currently no abuse-deterrent packaging systems for any of these CBTP products. The Sufentanil NanoTab BTP Management System is a novel system for the treatment of CBTP with pharmacokinetics that more closely match the timing of BTP episodes (i.e., shorter terminal half-life and a more consistent Tmax range than approved fentanyl-based products). Each NanoTab is dispensed via a small single-dose applicator (SDA), housed in a ”smart” dispenser that keeps an electronic dosing log to capture dispensing history and features a safe redosing indicator.
Methods: This Phase 2 study’s primary endpoint was the time-weighted summed pain intensity difference over 30 minutes (SPID30) following treatment. Secondary endpoints included reduction of pain intensity, pain relief, global medical performance assessment (GMPA) and the use of rescue medication. Forty-two patients were enrolled and received titration study medication. Patients who were successfully titrated to an effective and tolerable dose across the spectrum of available dosage strengths were randomized and received double-blind study medication. Thirty-six patients (86%) randomized into the double-blind treatment period. Failure to randomize were the result of two patients with adverse events (AE), two patients with lack of efficacy, one with non-compliance, and one with withdrawal of consent. The modified Intent-to-Treat (mITT) population included 33 patients for efficacy data analysis.
Results: For the mITT population, least squares (LS) mean (±SEM) of the time-weighted SPID30 scores were 59.9 (±6.25) and 42.6 (±6.86) in the active-treated episodes and placebo-treated episodes, respectively. The time-weighted SPID30 for the Sufentanil NanoTab-treated episodes was statistically significantly greater than placebo-treated episodes (p<0.001). For pain intensity (PI) at each evaluation time point, there were statistically significantly lower LS mean PI scores for active-treated episodes compared to placebo-treated episodes at the 15, 30, 45 and 60 minute time points (p=0.027 at 15 minutes and p<0.001 at all other time points).
Conclusions: This Phase 2 study demonstrates analgesic efficacy, safety and tolerability of the sublingual Sufentanil NanoTab in management of CBTP events in cancer patients. Future Phase 3 studies of the Sufentanil NanoTab BTP Management System will further delineate the safety and efficacy of this BTP system in both CBTP and non-cancer breakthrough pain.
Reg Anesth Pain Med 2010;