Trial Outcomes & Findings for Controlled Study to Assess the Efficacy and Safety of S-Ibuprofen Topical Gel 5% (AP0302) in the Treatment of DOMS (NCT NCT03852459)

Last Updated: 2022-01-25

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

251 participants

Primary outcome timeframe

0-24 hours.

Results posted on

2022-01-25

Participant Flow

This was a Phase 2/3, single-center study conducted in USA

A total of 434 subjects were screened in the study of which 251 subjects were randomized.

Participant milestones

Participant milestones
Measure	Active Arm S-Ibuprofen Topical Gel 5% AP0302 (S-ibuprofen topical gel 5%)applied up to 7 times in 24 hours, over a 48-hour dosing period.	Placebo Arm Vehicle Topical Gel Placebo topical gel 5% applied up to 7 times in 24 hours, over a 48-hour dosing period.
Overall Study STARTED	126	125
Overall Study COMPLETED	123	122
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Arm S-Ibuprofen Topical Gel 5% AP0302 (S-ibuprofen topical gel 5%)applied up to 7 times in 24 hours, over a 48-hour dosing period.	Placebo Arm Vehicle Topical Gel Placebo topical gel 5% applied up to 7 times in 24 hours, over a 48-hour dosing period.
Overall Study Adverse Event	2	2
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Arm n=126 Participants S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Placebo Arm n=125 Participants Vehicle Topical Gel Vehicle: Vehicle Gel	Total n=251 Participants Total of all reporting groups
Age, Continuous	28.2 years STANDARD_DEVIATION 10.41 • n=5 Participants	30.6 years STANDARD_DEVIATION 10.37 • n=7 Participants	29.4 years STANDARD_DEVIATION 10.44 • n=5 Participants
Sex: Female, Male Female	73 Participants n=5 Participants	68 Participants n=7 Participants	141 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	57 Participants n=7 Participants	110 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	102 Participants n=5 Participants	101 Participants n=7 Participants	203 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	102 Participants n=5 Participants	102 Participants n=7 Participants	204 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	16 Participants n=5 Participants	9 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	126 participants n=5 Participants	125 participants n=7 Participants	251 participants n=5 Participants
Body Mass Index (BMI)	24.01 kg/m^2 STANDARD_DEVIATION 3.146 • n=5 Participants	24.55 kg/m^2 STANDARD_DEVIATION 3.082 • n=7 Participants	24.28 kg/m^2 STANDARD_DEVIATION 3.120 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Arm n=126 Participants S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Placebo Arm n=125 Participants Vehicle Topical Gel Vehicle: Vehicle Gel
Sum of the Time-weighted Differences From Baseline in Pain Intensity With Movement(SPIDMOVE) Over 24 Hours Post Time Zero	-33.09 score on a scale*hours Standard Deviation 31.311	-29.09 score on a scale*hours Standard Deviation 29.763

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Active Arm n=126 Participants S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Placebo Arm n=125 Participants Vehicle Topical Gel Vehicle: Vehicle Gel
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. 24-48 hours	-60.37 score on a scale*hours Standard Deviation 38.168	-54.61 score on a scale*hours Standard Deviation 38.604
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. 0-36 hours	-59.64 score on a scale*hours Standard Deviation 48.384	-53.44 score on a scale*hours Standard Deviation 46.530
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. 36-48 hours	-33.82 score on a scale*hours Standard Deviation 20.293	-30.26 score on a scale*hours Standard Deviation 20.794
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. 0-48 hours	-93.47 score on a scale*hours Standard Deviation 66.331	-83.71 score on a scale*hours Standard Deviation 64.201
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. 0-6 hours	-4.82 score on a scale*hours Standard Deviation 5.478	-4.06 score on a scale*hours Standard Deviation 5.807
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. 6-12 hours	-8.98 score on a scale*hours Standard Deviation 8.583	-7.73 score on a scale*hours Standard Deviation 8.412
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. 0-12 hours	-13.80 score on a scale*hours Standard Deviation 13.435	-11.79 score on a scale*hours Standard Deviation 13.682
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. 12-24 hours	-19.29 score on a scale*hours Standard Deviation 18.868	-17.30 score on a scale*hours Standard Deviation 17.338
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. 24-36 hours	-26.55 score on a scale*hours Standard Deviation 18.582	-24.35 score on a scale*hours Standard Deviation 18.807

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Active Arm n=126 Participants S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Placebo Arm n=125 Participants Vehicle Topical Gel Vehicle: Vehicle Gel
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 24-36 hours	-23.33 score on a scale*hours Standard Deviation 21.209	-19.95 score on a scale*hours Standard Deviation 22.555
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 0-6 hours	-3.81 score on a scale*hours Standard Deviation 6.218	-3.33 score on a scale*hours Standard Deviation 5.957
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 6-12 hours	-7.75 score on a scale*hours Standard Deviation 9.893	-6.48 score on a scale*hours Standard Deviation 8.796
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 0-12 hours	-11.55 score on a scale*hours Standard Deviation 15.446	-9.81 score on a scale*hours Standard Deviation 14.302
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 12-24 hours	-17.20 score on a scale*hours Standard Deviation 20.476	-14.91 score on a scale*hours Standard Deviation 19.369
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 24-48 hours	-53.58 score on a scale*hours Standard Deviation 44.528	-44.77 score on a scale*hours Standard Deviation 44.732
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 0-36 hours	-52.08 score on a scale*hours Standard Deviation 54.840	-44.68 score on a scale*hours Standard Deviation 53.031
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 36-48 hours	-30.25 score on a scale*hours Standard Deviation 23.947	-24.82 score on a scale*hours Standard Deviation 23.171
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 0-24 hours	-28.75 score on a scale*hours Standard Deviation 34.920	-24.72 score on a scale*hours Standard Deviation 32.365
Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval 0-48 hours	-82.33 score on a scale*hours Standard Deviation 76.936	-69.49 score on a scale*hours Standard Deviation 73.804

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Active Arm n=126 Participants S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Placebo Arm n=125 Participants Vehicle Topical Gel Vehicle: Vehicle Gel
Total Relief With Movement (TOTPAR) 0-6 Hours Post Time Zero	4.06 score on a scale*hours Standard Deviation 3.435	3.61 score on a scale*hours Standard Deviation 3.978

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Active Arm n=126 Participants S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Placebo Arm n=124 Participants Vehicle Topical Gel Vehicle: Vehicle Gel
Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero Original Categories - Very good	9 Participants	5 Participants
Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero Original Categories - Poor	44 Participants	50 Participants
Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero Original Categories - Fair	48 Participants	47 Participants
Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero Original Categories - Good	25 Participants	21 Participants
Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero Original Categories - Excellent	0 Participants	1 Participants
Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero Dichotomized Categories - Poor/fair	92 Participants	97 Participants
Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero Dichotomized Categories - Good/very good/excellent	34 Participants	27 Participants

SECONDARY outcome

Timeframe: Up to Day 7

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

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.

Outcome measures

Outcome measures
Measure	Active Arm n=126 Participants S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Placebo Arm n=125 Participants Vehicle Topical Gel Vehicle: Vehicle Gel
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE with moderate in severity	6 participants	4 participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE with Severe in severity	0 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Subjects with any TEAE	125 participants	121 participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Subjects with any treatment-related TEAEs	124 participants	120 participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Subjects with TEAEs leading to discontinuation	2 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Subjects with SAEs	0 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE with mild in severity	119 participants	115 participants

Adverse Events

Active Arm

Serious events: 0 serious events

Other events: 123 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 0 serious events

Other events: 117 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Active Arm n=126 participants at risk S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Placebo Arm n=125 participants at risk Vehicle Topical Gel Vehicle: Vehicle Gel
General disorders application site erythema	97.6% 123/126 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.	93.6% 117/125 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.
General disorders application site induration	19.8% 25/126 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.	16.8% 21/125 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.
General disorders application site pain	55.6% 70/126 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.	10.4% 13/125 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.
General disorders application site pruritus	49.2% 62/126 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.	60.8% 76/125 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.
Musculoskeletal and connective tissue disorders musculoskeletal stiffness	6.3% 8/126 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.	6.4% 8/125 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.
Skin and subcutaneous tissue disorders skin exfoliation	21.4% 27/126 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.	3.2% 4/125 • Up to Day 7 TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.

Additional Information

Kenneth Corroon

Aponia Labs

Phone: 917-574-5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60