HTX-011

The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.

Pain intensity is assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-72 is 0-720. The prescribed activity for NRS-A is sitting with the plantar surface of the ball of the surgically attended foot touching the floor (no weight bearing).

Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". NRS scores are recorded with activity (NRS-A), sitting with the plantar surface of the ball of the surgically attended foot touching the floor (no weight-bearing).

Pain intensity is assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-24 is 0-240. The prescribed activity for NRS-A is keeping the elbows at the side and against the body and then raising both hands in front of the abdomen with hands clasped and holding that position for at least 5 seconds.

Pain intensity is assessed at rest using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-48 is 0-480.

Subjects assessed pain intensity for their current pain with the 11-point (0 to 10) Numeric Rating Scale NRS where "0" equated to "no pain" and "10" equated to "the worst pain imaginable". Pain intensity was assessed at rest (NRS-R) after the subject had been supine for a minimum of 5 minutes and with activity (NRS-A) sitting up from a supine position. The SPI is derived by summing the pain intensity score weighted by the scheduled time duration. SPI0-24 was calculated by summing the Pain intensity (PI) score at the relevant time points weighted by the scheduled time duration since the prior PI assessment as follows: SPI0-24= PI1+PI2+2\*PI4+2\*PI6+2\*PI8+2\*PI10+2\*PI12+2\*PI14+4\*PI18+6\*PI24. Min = 0 (if PI=0 at every time) and Max = 240 (if PI=10 at every time).

Summed Pain Intensity (SPI) Scores over the first 24 hours, which was the sum of the pain intensity scores at the scheduled 1 hour assessment, the assessments scheduled for every 2 hours between Hours 2 and 14, and the assessments scheduled at Hours 18 and 24; with the assessments at Hours 1 and 2 each weighted by 1, the assessments between Hours 4 and 14 each weighted by 2, the assessment at Hour 18 weighted by 4, and the assessment at Hour 24 weighted by 6. Pain was assessed using an 11-point scale, where 0 equaled no pain and 10 equaled the worst pain imaginable. Thus, the minimum and maximum possible SPI0-24 scores were 0 and 240, respectively.