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Abstract Title: A Phase 2 Open-Label Functionality, Safety, and Efficacy Study
of the Sufentanil NanoTab™ PCA System in Patients Following Elective
Unilateral Knee Replacement Surgery
Authors: David Griffin, MD, Vero Beach, FL
Roman Skowronski, MD, PhD, Redwood City, CA; Pamela Palmer, MD, PhD, Redwood City, CA
Introduction: Intravenous patient-controlled analgesia (IV PCA) with morphine is the standard of
care in many hospitals for the management of acute post-operative pain. However, IV PCA is
associated with several limitations, including, the risk of PCA pump programming errors, reduced
patient mobility secondary to the requisite IV line, and increased risk of analgesic gaps due to
infiltrated and dislodged IV catheters or pump malfunction. Furthermore, while morphine is the
most commonly used analgesic in this treatment modality, it can produce many undesirable side
effects due to accumulation of active metabolites, especially in elderly and renally impaired
patients. The Sufentanil NanoTab PCA System is a novel patient-controlled sublingual analgesia
(PCSA) product candidate with a pre-programmed patient lock-out feature that is designed for use
in hospital settings to provide effective, titratable, patient-controlled analgesia and reduce the risk
of programming errors. The Sufentanil NanoTab PCA System also avoids the IV-related limitations
of IV PCA by being designed to provide convenient and safe patient self-administration of Sufentanil
NanoTabs sublingually for oral transmucosal absorption.
Methods: This multicenter, open-label study enrolled 30 patients (mean age 65.7; range 51-78)
following elective unilateral knee replacement surgery. Nineteen patients (63.3%) were at least 65
years old. Patients self-administered 15 mcg doses of Sufentanil NanoTabs sublingually as needed
using the handheld Sufentanil NanoTab PCA System with a minimal re-dosing interval of 20
minutes. The primary efficacy endpoint was device functionality assessed as the proportion of
patients who successfully completed the study without any type of System failure.
Results: All enrolled patients (100%) completed the study without System failures or dosing errors
of any kind, which included over 375 dispensed NanoTabs. Twenty-five patients (83.3%) reported
the two highest scores on the 5-point Likert scale of overall patient’s satisfaction with the System.
All 30 enrolled patients indicated that they could handle the system easily and their user
instructions were clear. All 30 enrolled patients indicated that the dosing tone was sufficiently loud
and that the time required for dosing was just right. Twenty-seven patients (90%) indicated that
the size and the shape of the dosing tip was just right. The majority of patients indicated that the
other system features (weight, size, shape, and dose button function) were acceptable. The mean
pain intensity difference (PID) scores increased from 0.3 at 15 minutes to 2.4 at 3 hours. After 3
hours, the mean PID were variable and ranged from 1.3 to 2.0. Nineteen (63.3%) and 24 patients
(80%) responded very good or excellent on the patient global evaluation of pain relief and global
evaluation of tolerability, respectively. The most common related adverse events (AEs) were
vomiting (6 patients, 20.0%) and nausea (5 patients, 16.7%). All events were mild or moderate in
severity; no severe AEs were reported during the study. There were no serious AEs (SAEs) during
the study drug treatment or 12-hours after the end-of-treatment. One patient discontinued study
drug due to an AE of moderate anxiety that was judged as not related to study drug. There were no
reports of oral mucosa irritation.
Conclusions: The results of this Phase 2 study confirm the functionality, safety and efficacy of the
Sufentanil NanoTab PCA System in management of acute moderate-to-severe post-operative pain
following knee replacement surgery. Future Phase 3 studies of the Sufentanil NanoTab PCA System
will further delineate the safety and efficacy of this PCSA system.
Reg Anesth Pain Med 2010; 7