Controlled Study to Assess the Efficacy and Safety of S-Ibuprofen Topical Gel 5% (AP0302) in the Treatment of DOMS

The primary efficacy outcome is the sum of the time-weighted differences from baseline in muscle pain/soreness with movement over 0-24 hours post T0 (SPIDMOVE 0-24h), that is the area under the differences from baseline pain/soreness intensity difference curve. The pain intensity differences (PIDs) with movement from time point A to time point B was calculated using the trapezoid rule by subtracting each post-T0 pain score with movement from the pain score with movement at time point Ti. Positive and higher scores indicate greater reduction in pain. Measured by Pain Intensity Numerical Rating Scale (PI-NRS) where 0 = no pain and 10 = worst possible pain at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 20, 24, 26, 28, 30, 32, 34, 36, 40, 44, and 48 hours post-initial IP dose and immediately prior to the subsequent doses of investigational product (IP).

Time frame: 0-24 hours.

Population: Full Analysis Set: All subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.

TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug. A treatment-related TEAE was defined as a TEAE that was at least possibly related to the administration of study drug or was missing the relationship assessment. If a TEAE was recorded on multiple occasions, only the highest severity was presented.

Time frame: Up to Day 7

Population: Safety Population: All subjects who received at least 1 dose of study drug.

Sum of the time-weighted differences from baseline in pain intensity with movement (SPIDMOVE) over the following intervals: 0-6, 6-12, 0-12, 12-24, 24-36, 0-36, 24-28, 36-48, and 0-48 hours post-T0, that is the area under the differences from baseline pain/soreness intensity difference curve. The PIDs with movement from time point A to time point B was calculated using the trapezoid rule by subtracting each post-T0 pain score with movement from the pain score with movement at time point Ti. Positive and higher scores indicate greater reduction in pain. Measured by Pain Intensity Numerical Rating Scale (PI-NRS) where 0 = no pain and 10 = worst possible pain at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 20, 24, 26, 28, 30, 32, 34, 36, 40, 44, and 48 hours post-initial IP dose and immediately prior to the subsequent doses of IP.

Time frame: From 0-6, 6-12, 0-12, 12-24, 24-36, 0-36, 24-28,36-48, and 0-48 hours post-T0. Time point i included 1, 2, 3, 4, 5, 6 (pre-dose), 7, 8, 9, 10, 11, 12 (pre-dose), 16, 18 (pre-dose), 20, and 24 (pre-dose) hours after the first dose.

Population: Full Analysis Set: All subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.

Global assessment of efficacy will be assessed at approximately 48 hours post-T0 (or upon early termination if the subject withdraws prior to the 48-hour assessment). Subject Global Assessment Using Original 5 Categories as 0=poor, 1=fair, 2=good, 3=very good, 4=excellent. In addition, the 5 categories were dichotomized into 2 categories (good/very good/excellent versus poor/fair). The proportion of good, very good, and excellent ratings were calculated for each treatment.

Time frame: 48 hours post time zero

Population: Full Analysis Set: All subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.

Sum of the time-weighted differences from baseline in muscle stiffness with movement (SSIDMOVE) over the following intervals: 0-6, 6-12, 0-12, 12-24, 0-24, 24-36, 24-48, 0-36, 36-48, and 0-48 hours post-T0, that is the area under the differences from baseline stiffness difference curve. The muscle Stiffness Intensity Differences (SIDs) with movement from time point A to time point B was calculated using the trapezoid rule by subtracting each post-T0 stiffness score with movement from the stiffness score with movement at time point Ti. Positive and higher scores indicate greater reduction in stiffness. Measured by Muscle Stiffness Numerical Rating Scale (NRS) where 0 = No Stiffness and 10 = Worst Possible Stiffness at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 20, 24, 26, 28, 30, 32, 34, 36, 40, 44, and 48 hours post-initial IP dose and immediately prior to the subsequent doses of IP.

Time frame: 0-6, 6-12, 0-12, 12-24, 24-36, 24-48, 0-36, 36-48, and 0-48 post T0

Population: Full Analysis set: All subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.

Total relief with movement (TOTPAR) 0-6 hours post time zero TOTPAR was calculated as the sum of pain relief at time point i (PR i) times the weight for each PR i, where i referred to each pain relief scheduled assessment time point between A and B (not including B). The higher the number the better pain relief. Categorical Relief Rating Scale: Subjects rated relief from starting pain with movement using a 5-point categorical relief scale 0=no relief, 1=a little relief, 2=some relief, 3=a lot of relief, or 4=complete relief at 1, 2, 3, 4, 5, and 6 hours post-initial IP dose and immediately prior to a subsequent dose of IP if one occurred prior to 6 hours.

Time frame: 0-6 hours

Population: Full Analysis Set: All subjects who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline efficacy assessment.