Fentanyl Sublingual Spray for the Treatment of Moderate to Severe Post-Operative Pain

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[maximum(max)=10 at each time point\], and negative numbers indicate an increase in pain \[minimum(min)=-10 at each time point\]. The overall min and max are -10 and 10 times the number of hours specified; SPID-48 range is -480 to 480. The NRS SPID-48 was analyzed using an analysis of covariance (ANCOVA) model, which included treatment and site as main effects and Baseline pain intensity as the covariate.

Time frame: Over 0 to 48 hours after Time 0

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points after Time 0 (time of administration of the first dose of study drug). NRS PID is defined as the difference in pain at each scheduled time point relative to Baseline (PID=pain intensity at baseline - pain intensity at time point). A higher value of NRS PID score indicates a higher decrease in pain from Baseline. NRS PID is reported as the least squares mean difference.

Time frame: Baseline, 1, 16, and 24 hours

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points after Time 0 (time of administration of the first dose of study drug). A lower value indicates improvement in pain.

Time frame: Baseline, 1, 16, and 24 hours

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain \[maximum(max)=10 at each timepoint\], and negative numbers indicate an increase in pain \[minimum(min)=-10 at each timepoint\]. The overall min and max are -10 and 10 times the number of hours specified: SPID-4=(-40 to 40), SPID-8=(-80 to 80) and SPID-24=(-240 to 240). The NRS SPID-4, 8 and 24 were analyzed using an ANCOVA model which included treatment and site as main effects and Baseline pain intensity as the covariate.

Time frame: Over 0 to 4 hours (NRS SPID-4), over 0 to 8 hours (NRS SPID-8), and over 0 to 24 hours (NRS SPID-24)

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Time frame: Over 0 to 24 hours; Over 0 to 48 hours

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Time frame: Within 48 hours

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Pain relief is determined on a 5-point categorical scale where 0=none, 1=a little, 2=some, 3=a lot, 4=complete.

Time frame: 2.5, 5, 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 32, 40, and 48 hours, as well as immediately before each use of rescue analgesia

Population: All randomized participants from the Intent-to-Treat (ITT) population. The number analyzed differs in the later time points for the Fentanyl groups because some participants withdrew over the course of the study.

Participants provide a global evaluation of study drug on a 5-point categorical scale where 0=poor, 1=fair, 2=good, 3=very good, and 4=excellent.

Time frame: Within 48 hours

Population: All randomized participants from the Intent-to-Treat (ITT) population.

The highest level of pain relief achieved on a 5-point categorical scale where 0=none, 1=a little, 2=some, 3=a lot, 4=complete.

Time frame: Within 48 hours after Time 0

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Time to perceptible and meaningful pain relief will be evaluated using the 2-stopwatch method (after the first dose only) (2 stopwatches will be started as soon as the first dose of study drug is administered. Each participant will be instructed to stop the first stopwatch when he or she experiences any perceptible pain relief and the second stopwatch when he or she experiences pain relief that is meaningful to them.)

Time frame: Within 48 hours after Time 0

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Time frame: Within 48 hours

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Time to perceptible and meaningful pain relief will be evaluated using the 2-stopwatch method (after the first dose only) (2 stopwatches will be started as soon as the first dose of study drug is administered. Each participant will be instructed to stop the first stopwatch when he or she experiences any perceptible pain relief and the second stopwatch when he or she experiences pain relief that is meaningful to them.)

Time frame: Within 48 hours after Time 0

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Time frame: Within 48 hours after Time 0

Population: All randomized participants from the Intent-to-Treat (ITT) population.

Measured as time to perceptible pain relief confirmed by meaningful pain relief using the 2-stopwatch method (2 stopwatches will be started as soon as the first dose of study drug is administered. Each participant will be instructed to stop the first stopwatch when he or she experiences any perceptible pain relief and the second stopwatch when he or she experiences pain relief that is meaningful to them.)

Time frame: Within 48 hours

Population: All randomized participants from the Intent-to-Treat (ITT) population.

TOTPAR was assessed by the participant using a 5-point NRS (0=no relief, 1=a little, 2=some, 3=a lot, 4=complete relief). TOTPAR scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (first dose of study drug). The TOTPAR scores are the sum of the pain relief at each time point multiplied by the duration in hours since the previous time point. Larger positive numbers indicate more pain relief (maximum=4 at each time point) and smaller positive numbers indicate less pain relief (minimum=0 at each time point). The overall minimum is 0 for each variable and the overall maximum is 4 times the number of hours specified for the variable: TOTPAR-4=(0 to 16), TOTPAR-8=(0 to 32), TOTPAR-24=(0 to 96) and TOTPAR-48=(0 to 192). TOTPAR-4, TOTPAR-8, TOTPAR-24 and TOTPAR-48 were analyzed using an ANCOVA model with factors for treatment, site and baseline pain intensity.

Time frame: Over 0 to 4 hours (TOTPAR-4), over 0 to 8 hours (TOTPAR-8), over 0 to 24 hours (TOTPAR-24), and over 0 to 48 hours (TOTPAR-48)

Population: All randomized participants from the Intent-to-Treat (ITT) population.