Safety, Efficacy, and Pharmacokinetics of SKY0402 Administered as a Nerve Block in Subjects Undergoing Bunionectomy
The primary objective of this study was to determine the appropriate dose of SKY0402 administered as a nerve block for the management of postoperative pain following bunionectomy.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase 2, Multicenter, Randomized, Double Blind, Dose Escalating/ De-Escalating Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Sustained Release Encapsulated Bupivacaine (SKY0402) Administered as a Nerve Block in the Management of Postoperative Pain in Subjects Undergoing Bunionectomy|
- Time to First Use of Supplemental Pain Medication Postoperatively for Surgical Pain [ Time Frame: Through 96 hours postdose ] [ Designated as safety issue: No ]The primary efficacy endpoint was the time to first use of supplemental pain medication (opioid or non-opioid) postoperatively for surgical pain.
- Number of Patients With Adverse Events [ Time Frame: Through 30 days postdose ] [ Designated as safety issue: Yes ]All adverse events were to be recorded from the time of dosing through Day 8. Serious adverse events (SAEs) were to be recorded through Day 30.
|Study Start Date:||March 2005|
|Study Completion Date:||December 2006|
|Primary Completion Date:||March 2006 (Final data collection date for primary outcome measure)|
Active Comparator: SKY0402
Low-dose, low-mid dose, and mid-dose
Single dose of SKY0402 administered as a nerve block
Active Comparator: Bupivacaine HCl
Marcaine with epinephrine 1:200,000 is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402
Drug: Bupivacaine HCl
Single dose of 125 mg administered as a nerve block
This Phase 2, multicenter, randomized, double blind, dose escalating/de-escalating study evaluated the safety, efficacy, and pharmacokinetics of a single dose of SKY0402 compared to a single 125 mg dose of bupivacaine HCl for the treatment of postoperative pain in subjects undergoing bunionectomy.
Up to 88 subjects were to be randomized in five consecutive cohorts. The dose of bupivacaine HCl (125 mg) was to remain constant for all cohorts. After completion of Cohort 1, the decision to increase or decrease the dose of SKY0402 was made by a Cohort Data Review Committee following a review of pharmacokinetic, safety, and selected efficacy data from the previous cohort.
Study drug was to be administered as an ankle block, with or without a tourniquet, between 1 hour before the induction of general anesthesia and 20 minutes before the end of general anesthesia. The ankle block procedure consisted of five injections via three skin entries targeting the following nerves: posterior tibial, sural, deep peroneal, superficial peroneal, and saphenous.
The use of intravenous fentanyl during general anesthesia was permitted, but was not to exceed 250 micrograms. The intraoperative use of morphine was prohibited. Postoperatively, subjects had access to both opioid and non-opioid supplemental pain medication under general guidelines. Blood samples for the determination of plasma bupivacaine concentrations were obtained at Baseline and at specified time points through 96 hours.