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

Study Overview
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Brief Summary
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Phase 2 study designed to evaluated analgesic efficacy and safety of S-Ibuprofen Topical Gel 5%

Detailed Description
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The purpose of this randomized, double-blind study is to evaluate the efficacy and safety of S-Ibuprofen Topical Gel 5% in reducing pain/soreness associated with delayed onset muscle soreness (DOMS).

Official Title
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A Randomized, Double-Blind,Vehicle-Controlled Study to Determine the Efficacy and Safety of AP0302 in the Treatment of Delayed Onset Muscle Soreness (DOMS)

Conditions
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Pain, Acute

Intervention / Treatment
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* Drug: S-Ibuprofen
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: history of pain/soreness after exercise BMI between 18-30 negative drug, alcohol, pregnancy screens other protocol-defined inclusion criteria may apply Exclusion Criteria: upper extremity workout in last 3 months job or hobby requiring heavy lifting history of muscle disorders allergy or intolerance to NSAID or study drug history of recent pain medication use other protocol-defined exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Arm<br>S-Ibuprofen Topical Gel 5% | Drug: S-Ibuprofen<br>* Topical Gel 5%<br>|
| Placebo Comparator: Placebo Arm<br>Vehicle Topical Gel | Drug: Vehicle<br>* Vehicle Gel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of the Time-weighted Differences From Baseline in Pain Intensity With Movement(SPIDMOVE) Over 24 Hours Post Time Zero | 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). | 0-24 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SPIDMOVE Over the Following Intervals: 0-6, 6-12, 0-12, 12-24, 24-36, 24-48, 0-36, 36-48 and 0-48 Hours Post-T0. | 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. | 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. | 
| Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval | 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. | 0-6, 6-12, 0-12, 12-24, 24-36, 24-48, 0-36, 36-48, and 0-48 post T0 | 
| Total Relief With Movement (TOTPAR) 0-6 Hours Post Time Zero | 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. | 0-6 hours | 
| Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero | 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. | 48 hours post time zero | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | Up to Day 7 |