Title

Controlled Study to Assess the Efficacy and Safety of S-Ibuprofen Topical Gel 5% (AP0302) in the Treatment of DOMS
A Randomized, Double-Blind,Vehicle-Controlled Study to Determine the Efficacy and Safety of AP0302 in the Treatment of Delayed Onset Muscle Soreness (DOMS)
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Study Participants

    251
Phase 2 study designed to evaluated analgesic efficacy and safety of S-Ibuprofen Topical Gel 5%
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).
Study Started
Jan 12
2018
Primary Completion
Apr 04
2019
Study Completion
Apr 11
2019
Results Posted
Jan 25
2022
Last Update
Jan 25
2022

Drug S-Ibuprofen

Topical Gel 5%

Drug Vehicle

Vehicle Gel

Placebo Arm Placebo Comparator

Vehicle Topical Gel

Active Arm Experimental

S-Ibuprofen Topical Gel 5%

Criteria

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

Summary

Active Arm

Placebo Arm

All Events

Event Type Organ System Event Term Active Arm Placebo Arm

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).

Active Arm

-33.09
score on a scale*hours (Mean)
Standard Deviation: 31.311

Placebo Arm

-29.09
score on a scale*hours (Mean)
Standard Deviation: 29.763

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.

Active Arm

0-12 hours

-13.8
score on a scale*hours (Mean)
Standard Deviation: 13.435

0-36 hours

-59.64
score on a scale*hours (Mean)
Standard Deviation: 48.384

0-48 hours

-93.47
score on a scale*hours (Mean)
Standard Deviation: 66.331

0-6 hours

-4.82
score on a scale*hours (Mean)
Standard Deviation: 5.478

12-24 hours

-19.29
score on a scale*hours (Mean)
Standard Deviation: 18.868

24-36 hours

-26.55
score on a scale*hours (Mean)
Standard Deviation: 18.582

24-48 hours

-60.37
score on a scale*hours (Mean)
Standard Deviation: 38.168

36-48 hours

-33.82
score on a scale*hours (Mean)
Standard Deviation: 20.293

6-12 hours

-8.98
score on a scale*hours (Mean)
Standard Deviation: 8.583

Placebo Arm

0-12 hours

-11.79
score on a scale*hours (Mean)
Standard Deviation: 13.682

0-36 hours

-53.44
score on a scale*hours (Mean)
Standard Deviation: 46.530

0-48 hours

-83.71
score on a scale*hours (Mean)
Standard Deviation: 64.201

0-6 hours

-4.06
score on a scale*hours (Mean)
Standard Deviation: 5.807

12-24 hours

-17.3
score on a scale*hours (Mean)
Standard Deviation: 17.338

24-36 hours

-24.35
score on a scale*hours (Mean)
Standard Deviation: 18.807

24-48 hours

-54.61
score on a scale*hours (Mean)
Standard Deviation: 38.604

36-48 hours

-30.26
score on a scale*hours (Mean)
Standard Deviation: 20.794

6-12 hours

-7.73
score on a scale*hours (Mean)
Standard Deviation: 8.412

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.

Active Arm

0-12 hours

-11.55
score on a scale*hours (Mean)
Standard Deviation: 15.446

0-24 hours

-28.75
score on a scale*hours (Mean)
Standard Deviation: 34.920

0-36 hours

-52.08
score on a scale*hours (Mean)
Standard Deviation: 54.840

0-48 hours

-82.33
score on a scale*hours (Mean)
Standard Deviation: 76.936

0-6 hours

-3.81
score on a scale*hours (Mean)
Standard Deviation: 6.218

12-24 hours

-17.2
score on a scale*hours (Mean)
Standard Deviation: 20.476

24-36 hours

-23.33
score on a scale*hours (Mean)
Standard Deviation: 21.209

24-48 hours

-53.58
score on a scale*hours (Mean)
Standard Deviation: 44.528

36-48 hours

-30.25
score on a scale*hours (Mean)
Standard Deviation: 23.947

6-12 hours

-7.75
score on a scale*hours (Mean)
Standard Deviation: 9.893

Placebo Arm

0-12 hours

-9.81
score on a scale*hours (Mean)
Standard Deviation: 14.302

0-24 hours

-24.72
score on a scale*hours (Mean)
Standard Deviation: 32.365

0-36 hours

-44.68
score on a scale*hours (Mean)
Standard Deviation: 53.031

0-48 hours

-69.49
score on a scale*hours (Mean)
Standard Deviation: 73.804

0-6 hours

-3.33
score on a scale*hours (Mean)
Standard Deviation: 5.957

12-24 hours

-14.91
score on a scale*hours (Mean)
Standard Deviation: 19.369

24-36 hours

-19.95
score on a scale*hours (Mean)
Standard Deviation: 22.555

24-48 hours

-44.77
score on a scale*hours (Mean)
Standard Deviation: 44.732

36-48 hours

-24.82
score on a scale*hours (Mean)
Standard Deviation: 23.171

6-12 hours

-6.48
score on a scale*hours (Mean)
Standard Deviation: 8.796

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.

Active Arm

4.06
score on a scale*hours (Mean)
Standard Deviation: 3.435

Placebo Arm

3.61
score on a scale*hours (Mean)
Standard Deviation: 3.978

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.

Active Arm

Dichotomized Categories - Good/very good/excellent

Dichotomized Categories - Poor/fair

Original Categories - Excellent

Original Categories - Fair

Original Categories - Good

Original Categories - Poor

Original Categories - Very good

Placebo Arm

Dichotomized Categories - Good/very good/excellent

Dichotomized Categories - Poor/fair

Original Categories - Excellent

Original Categories - Fair

Original Categories - Good

Original Categories - Poor

Original Categories - Very good

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.

Active Arm

Subjects with any TEAE

125.0
participants

Subjects with any treatment-related TEAEs

124.0
participants

Subjects with SAEs

Subjects with TEAEs leading to discontinuation

2.0
participants

TEAE with mild in severity

119.0
participants

TEAE with moderate in severity

6.0
participants

TEAE with Severe in severity

Placebo Arm

Subjects with any TEAE

121.0
participants

Subjects with any treatment-related TEAEs

120.0
participants

Subjects with SAEs

Subjects with TEAEs leading to discontinuation

2.0
participants

TEAE with mild in severity

115.0
participants

TEAE with moderate in severity

4.0
participants

TEAE with Severe in severity

2.0
participants

Total

251
Participants

Age, Continuous

29.4
years (Mean)
Standard Deviation: 10.44

Body Mass Index (BMI)

24.28
kg/m^2 (Mean)
Standard Deviation: 3.120

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Sex: Female, Male

Overall Study

Active Arm

Placebo Arm

Drop/Withdrawal Reasons

Active Arm

Placebo Arm