Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
SKY0402 · 13 trials · 8 indications
To assess pain intensity at rest (NRS-R), the subject was to assume a resting position that did not exacerbate his or her postoperative pain and respond to the following question: "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain are you having right now?"
The AUC of the NRS-R pain intensity scores from time 0 through 24 hours The subject was to rest for at least 5 minutes before responding to the following question, "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain are you having right now?"
The subject's pain intensity was assessed with activity (NRS-A), while actively flexing the involved knee from the maximum extension point to the maximum flexion point possible. The subject responded to the following question, "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain did you have while bending your knee?"
Assessments of postoperative pain were conducted through 96 hours and included pain intensity at rest (NRS-R) and with activity (NRS-A). The prescribed activity was to consist of raising the arm, in full extension at the elbow and wrist, to a position parallel with the axis of the torso. Pain intensity was scored on an 11-point scale, where 0 = no pain and 10 = worst possible pain.
To assess pain intensity at rest (NRS-R), the subject was to assume a resting position that did not exacerbate his or her postoperative pain. The subject was to rest in this position for at least 5 minutes before responding to the following question: "On a scale of 0 to 10, where 0=no pain and 10=worst possible pain, how much pain are you having right now?"
The subject's pain intensity was to be assessed with activity (NRS-A), after the subject had moved himself from a supine position in bed to a sitting up position at the edge of the bed. The subject was to respond to the following question: "On a scale of 0 to 10, where 0=no pain and 10=worst possible pain, how much pain did you have while sitting up?"
The subject's pain intensity was to be assessed with activity (NRS-A) after actively flexing the involved knee to the maximum flexion point possible. The subject was asked to respond to the following question: "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain did you have while bending your knee?"
The primary efficacy endpoint was the time to first use of supplemental pain medication (opioid or non-opioid) postoperatively for surgical pain.
The primary efficacy endpoint was the time to first use of supplemental pain medication (opioid or non-opioid) postoperatively for surgical wound pain
A dynamometer was used to measure the force produced during a maximum voluntary isometric contraction (MVIC) in a seated position with the knees flexed at 90°. The dynamometer was placed on the anterior tibia perpendicular to the tibial crest, just proximal to the medial malleolus. Subjects were asked to take 2 seconds to come to maximum effort contracting the ipsilateral quadriceps femoris, maintain this effort for 5 seconds, and then relax. The measurements immediately before study drug administration were designated baseline, and all subsequent are expressed as a percentage of the baseline.
| Arm | Type | Description |
|---|---|---|
| SKY0402 | EXPERIMENTAL | During the hemorrhoidectomy, 30cc of SKY0402 is injected into the wound. |
| Placebo | PLACEBO_COMPARATOR | During the hemorrhoidectomy, 30cc Placebo injected into the wound. |
| Bupivacaine HCl | ACTIVE_COMPARATOR | 100 mg Bupivacaine HCl (e.g., Marcaine with epinephrine 1:200,000) is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402. A single dose of study drug was administered intraoperatively (at the end of surgery) via local infiltration. |
| Low-dose SKY0402 + bupivacaine HCl | ACTIVE_COMPARATOR | Marcaine with epinephrine 1:200,000 is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402 |
| Mid-dose SKY0402 + bupivacaine HCl | ACTIVE_COMPARATOR | Marcaine with epinephrine 1:200,000 is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402 |
| SKY0402 high dose | EXPERIMENTAL | SKY0402, single administration |
| SKY0402 middle dose | EXPERIMENTAL | SKY0402, single administration |
| SKY0402 low dose | EXPERIMENTAL | SKY0402, single administration |
| Bupivacaine HCl 105mg | ACTIVE_COMPARATOR | Bupivacaine HCl given during hernia repair |
| Nerve Block | EXPERIMENTAL | The dominant side (left or right) will be randomized to one of two treatment groups: the higher or lower concentration of the local anesthetic EXPAREL. The non-dominant contralateral side will receive the other possible treatment. The volume of each and every single-injection femoral nerve block will be 30 mL (standard for femoral nerve blocks is 30-40 mL).3 Since volume will remain constant, we will vary the dose of EXPAREL by varying concentration (volume x concentration = dose). Of note, EXPAREL may be mixed with normal saline to vary the concentration. Randomization will be based on computer-generated codes. Randomization will be in blocks of two, and stratified by sex. |
| Moxifloxacin tablet | ACTIVE_COMPARATOR | - |
| Placebo tablet | EXPERIMENTAL | - |
| SKY0402 300mg | EXPERIMENTAL | - |
| SKY0402 450mg | EXPERIMENTAL | - |
| Placebo injection | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| SKY0402 | DRUG | During the operation, 30cc of SKY0402 are injected into the wound. |
| Placebo | DRUG | During the hemorrhoidectomy, 30cc Placebo injected into the wound. |
| Bupivacaine HCl | DRUG | 100 mg Bupivacaine HCl |
| SKY0402 + bupivacaine HCl | DRUG | Low-dose SKY0402 administered locally into one breast pocket and 75 mg bupivacaine HCl administered locally into the other breast pocket |
| Mid-dose SKY0402 + bupivacaine HCl | DRUG | Mid-dose SKY0402 administered locally into one breast pocket and 75 mg bupivacaine HCl administered locally into the other breast pocket |
| Moxifloxacin 400mg | DRUG | - |
| Placebo injection | DRUG | - |
| Placebo tablet | DRUG | - |
Inclusion Criteria: * Age \> 18 years of age at the Screening visit * American Society of Anesthesiologists (ASA) class 1-3 * Scheduled to have a two or three column excisional hemorrhoidectomy under general anesthesia using the Milligan-Morgan technique * For female subjects, surgically sterile or...