"In this trial, all of the primary and secondary objectives were met by
showing patients could be successfully converted from oral opioids such as
OxyContin(R) and from fentanyl patches such as Duragesic(R) to
TRANSDUR-Sufentanil, while also showing a reduction in pain scores on our
In addition to the recent Phase IIb study, there have been 9 additional clinical studies performed to date with TRANSDUR-Sufentanil that have involved over 300 patient exposures. These studies include evaluating wearing, pharmacokinetics, specialty populations, repeat applications, skin abrasions, drug interactions and dose conversions. In addition, a non-clinical package comprising multiple animal safety studies has been developed, including carcinogenicity studies, long-term toxicology and multiple biocompatibility studies.
Phase IIb Trial
-- Primary objective: explore the minimally acceptable dose titration interval for transitioning opioid experienced patients to TRANSDUR-Sufentanil to achieve an acceptable analgesic and side effect profile.
-- Secondary objectives:
-- Evaluate the relative potency relationship for converting patients
from current opioid therapy to TRANSDUR-Sufentanil;
-- Evaluate the efficacy of TRANSDUR-Sufentanil administration; and
-- Evaluate the safety and tolerability (including local effects) of continuous TRANSDUR-Sufentanil administration at a dose delivering adequate pain control.
The TRANSDUR-Sufentanil Phase IIb clinical trial was an open label, two-stage study to explore the titration (conversion) schedule for transitioning opioid-experienced patients with non-malignant moderate to severe chronic pain from current oral (e.g., OxyContin(R)) and transdermal opioid (e.g., Duragesic(R)) therapies to TRANSDUR-Sufentanil. After screening and recording of baseline (before TRANSDUR-Sufentanil therapy) measurements with respect to average pain intensity and other matters, patients were randomized into multiple titration regimens. After achieving an endpoint of adequate, stable pain control and an acceptable safety profile on TRANSDUR-Sufentanil, patients entered a 28-day continuous treatment maintenance period, followed by a 7-day follow-up period to ensure that an adequate pain control regimen was re-established. In this study conducted at 11 sites in the U.S., a total of 74 patients entered screening, of which 36 entered the maintenance period.
Dose Titration Interval
In this study, approximately half (36 out of 74) of the screened patients successfully entered the maintenance period, which is consistent with expectations for the study and with other chronic pain studies of a similar nature. After exploring multiple dose titration regimens, two acceptable dose titration intervals have achieved the desired analgesic effect and side-effect profile, and therefore are expected to be utilized in Phase III.
As a result of converting screened patients to stable pain control and into the maintenance period (see above), the conversion ratios from oral morphine equivalents at baseline to TRANSDUR-Sufentanil dosage strengths were established and are expected to be utilized in the Phase III program.
Although not the main goal of the study, the mean pain score during the maintenance period of 3.88 (on a numerical ratings scale for pain intensity of 0-10, with 0 being no pain) represented a reduction of approximately 19% from the mean baseline pain score of 4.78. These pain scores represent the mean for the patients that had a maintenance pain value and a baseline pain value (n=36) and computations were based on the intention-to-treat patients set. Only 1 patient out of 36 (approximately 2.8%) dropped out of the study during the maintenance period for lack of efficacy.
Safety and Tolerability
The safety summary is consistent with commonly expected adverse events using transdermal therapy systems with opioids. Only 1 out of 74 patients (approximately 1.4%) dropped out of the study due to application site reaction (local pruritis) and that one instance occurred during the first visit. No patients dropped out of the study due to application site adverse events during the maintenance period. No patients' adverse events were rated as severe.
TRANSDUR-Sufentanil is intended to provide continuous delivery of sufentanil for up to seven days from a single application, as compared to the two to three days of relief provided by currently available opioid patches. We anticipate that the small size of our sufentanil patch (potentially as small as 1/5th the size of currently marketed transdermal fentanyl patches for a therapeutically equivalent dose) and longer duration of action may offer meaningful patient benefits for chronic pain sufferers. We believe that the product profile of TRANSDUR-Sufentanil may allow such patches to compete effectively in the chronic pain market including both patches and oral opioids.
NOTE: POSIDUR(TM), SABER(TM), ORADUR(TM), TRANSDUR(TM), and ELADUR(TM) are
DURECT Forward-Looking Statement
The statements in this press release regarding TRANSDUR-Sufentanil, its
potential attributes and product benefits, its potential as an alternative to
opioid products, anticipated Phase III program (including the dose titration
regimens and dose conversion ratios expected to be utilized in the Phase III
program) and regulatory pathway for approval, our intentions to enter into
collaborations or further develop the program are forward-looking statements
involving risks and uncertainties that can cause actual results to differ
materially from those in such forward-looking statements. Potential risks and
uncertainties include, but are not limited to, the uncertainty and costs
associated with the development and commercialization of certain opioid drug
products such as TRANSDUR-Sufentanil due to increased scrutiny and possible
new regulations relating to risk evaluation and mitigation of these drugs, our
difficulty or failure to obtain approvals from regulatory agencies with
respect to TRANSDUR-Sufentanil, design, enroll, conduct and complete clinical
trials, complete the design, development, and manufacturing process
development of TRANSDUR-Sufentanil, consummate collaborative agreements
relating to TRANSDUR-Sufentanil, manufacture and commercialize and obtain
marketplace acceptance of TRANSDUR-Sufentanil, avoid infringing patents held
by other parties and secure and defend patents of our own, and manage and
obtain capital to fund our growth, operations and expenses. Further
information regarding these and other risks is included in
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