Study 1: Infiltration for Bunionectomy in Adults

A multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (NCT00890682) (Study 1) evaluated the safety and efficacy of 106 mg (8 mL) bupivacaine liposome injectable suspension in 193 adult patients undergoing bunionectomy. The mean age was 43 years (range 18 to 72).

Study medication was administered directly into the site at the conclusion of the surgery, prior to closure. There was an infiltration of placebo or 7 mL of bupivacaine liposome injectable suspension into the tissues surrounding the osteotomy and 1 mL into the subcutaneous tissue.

Pain intensity was rated by the patients on a 0 to 10 numeric rating scale (NRS) out to 72 hours. Postoperatively, patients were allowed rescue medication (5 mg oxycodone/325 mg acetaminophen orally every 4 to 6 hours as needed) or, if that was insufficient within the first 24 hours, ketorolac (15 to 30 mg IV). The primary outcome measure was the area under the curve (AUC) of the NRS pain intensity scores (cumulative pain scores) collected over the first 24-hour period. There was a significant treatment effect for bupivacaine liposome injectable suspension compared to placebo. Bupivacaine liposome injectable suspension demonstrated a significant reduction in pain intensity compared to placebo for up to 24 hours. There was no significant difference in the amount of morphine equivalents used through 72 hours post-surgery, 43 mg versus 42 mg for placebo and bupivacaine liposome injectable suspension, respectively. In addition, there was not a significant difference in the percentage of patients that used ketorolac, 43% versus 31% for placebo and bupivacaine liposome injectable suspension, respectively. 

Study 2: Infiltration for Hemorrhoidectomy in Adults

A multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (NCT00890721) (Study 2) evaluated the safety and efficacy of 266 mg (20 mL) bupivacaine liposome injectable suspension in 189 adult patients undergoing hemorrhoidectomy. The mean age was 48 years (range 18 to 86).

Bupivacaine liposome injectable suspension or placebo were administered directly into the site (greater than or equal to 3 cm) at the conclusion of the surgery. Dilution of 20 mL of bupivacaine liposome injectable suspension with 10 mL of saline, for a total of 30 mL, was divided into six 5-mL aliquots. A field block was performed by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers.

Pain intensity was rated by the patients on a 0 to 10 NRS at multiple time points up to 72 hours. Postoperatively, patients were allowed rescue medication (morphine sulfate 10 mg intramuscular every 4 hours as needed).

The primary outcome measure was the AUC of the NRS pain intensity scores (cumulative pain scores) collected over the first 72-hour period.

There was a significant treatment effect for bupivacaine liposome injectable suspension compared to placebo. See Figure 1 for the mean pain intensity over time for the bupivacaine liposome injectable suspension and placebo treatment groups for the 72- hour efficacy period. 

Figure 1. Mean Pain Intensity versus Time plot for hemorrhoidectomy study (C-316)

There were statistically significant, but small differences in the amount of opioid rescue analgesia used across the treatment groups, the clinical benefit of which has not been established. The median time to rescue analgesic use was 15 hours for patients treated with bupivacaine liposome injectable suspension and one hour for patients treated with placebo. Twenty-eight percent of patients treated with bupivacaine liposome injectable suspension required no rescue medication at 72 hours compared to 10% treated with placebo. For those patients who did require rescue medication, the mean amount of morphine sulfate intramuscular injections used over 72 hours was 22 mg for patients treated with bupivacaine liposome injectable suspension and 29 mg for patients treated with placebo.