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

• Sponsor: Aponia Laboratories, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03852459
• Collaborator: (none)
• Enrollment: 251
• Location: 1
• Arms: 2
• Actual Duration (Months): 14.9
• Patients Per Site Per Month: 16.8

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pain, Acute	Drug: S-Ibuprofen; Drug: Vehicle	Phase 2

Detailed Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 251 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: active gel and matching vehicle control gel
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind,Vehicle-Controlled Study to Determine the Efficacy and Safety of AP0302 in the Treatment of Delayed Onset Muscle Soreness (DOMS)
• Actual Study Start Date: Jan 12, 2018
• Actual Primary Completion Date: Apr 4, 2019
• Actual Study Completion Date: Apr 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Arm S-Ibuprofen Topical Gel 5%	Drug: S-Ibuprofen; Topical Gel 5%
Placebo Comparator: Placebo Arm Vehicle Topical Gel	Drug: Vehicle; Vehicle Gel

Outcome Measures

Primary Outcome Measures

1. Sum of the Time-weighted Differences From Baseline in Pain Intensity With Movement(SPIDMOVE) Over 24 Hours Post Time Zero [0-24 hours.]

   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).

Secondary Outcome Measures

1. 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. [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 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.

2. Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval [0-6, 6-12, 0-12, 12-24, 24-36, 24-48, 0-36, 36-48, and 0-48 post T0]

   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.

3. Total Relief With Movement (TOTPAR) 0-6 Hours Post Time Zero [0-6 hours]

   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.

4. Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero [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.

5. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [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. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	JBR Clinical Research	Salt Lake City	Utah	United States	84107

Sponsors and Collaborators

• Aponia Laboratories, Inc.

Investigators

• Principal Investigator: Todd Bertoch, MD, JBR Research

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 2, 2018

More Information

Publications

None provided.

• Responsible Party: Aponia Laboratories, Inc.
• ClinicalTrials.gov Identifier: NCT03852459
• Other Study ID Numbers: AP-007
• First Posted: Feb 25, 2019
• Last Update Posted: Jan 25, 2022
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Acute Pain; Ibuprofen

Study Results

Participant Flow

Recruitment Details	This was a Phase 2/3, single-center study conducted in USA
Pre-assignment Detail	A total of 434 subjects were screened in the study of which 251 subjects were randomized.

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	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.	Vehicle Topical Gel Placebo topical gel 5% applied up to 7 times in 24 hours, over a 48-hour dosing period.
Period Title: Overall Study
STARTED	126	125
COMPLETED	123	122
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Active Arm	Placebo Arm	Total
Arm/Group Description	S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Vehicle Topical Gel Vehicle: Vehicle Gel	Total of all reporting groups
Overall Participants	126	125	251
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.2 (10.41)	30.6 (10.37)	29.4 (10.44)
Sex: Female, Male (Count of Participants)
Female	73 57.9%	68 54.4%	141 56.2%
Male	53 42.1%	57 45.6%	110 43.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 19%	24 19.2%	48 19.1%
Not Hispanic or Latino	102 81%	101 80.8%	203 80.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	3 2.4%	3 1.2%
Asian	6 4.8%	9 7.2%	15 6%
Native Hawaiian or Other Pacific Islander	1 0.8%	0 0%	1 0.4%
Black or African American	1 0.8%	2 1.6%	3 1.2%
White	102 81%	102 81.6%	204 81.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	16 12.7%	9 7.2%	25 10%
Region of Enrollment (participants) [Number]
United States	126 100%	125 100%	251 100%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.01 (3.146)	24.55 (3.082)	24.28 (3.120)

Outcome Measures

1. Primary Outcome

Title	Sum of the Time-weighted Differences From Baseline in Pain Intensity With Movement(SPIDMOVE) Over 24 Hours Post Time Zero
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Vehicle Topical Gel Vehicle: Vehicle Gel
Measure Participants	126	125
Mean (Standard Deviation) [score on a scale*hours]	-33.09 (31.311)	-29.09 (29.763)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active Arm, Placebo Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4272
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	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.
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Vehicle Topical Gel Vehicle: Vehicle Gel
Measure Participants	126	125
0-6 hours	-4.82 (5.478)	-4.06 (5.807)
6-12 hours	-8.98 (8.583)	-7.73 (8.412)
0-12 hours	-13.80 (13.435)	-11.79 (13.682)
12-24 hours	-19.29 (18.868)	-17.30 (17.338)
24-36 hours	-26.55 (18.582)	-24.35 (18.807)
24-48 hours	-60.37 (38.168)	-54.61 (38.604)
0-36 hours	-59.64 (48.384)	-53.44 (46.530)
36-48 hours	-33.82 (20.293)	-30.26 (20.794)
0-48 hours	-93.47 (66.331)	-83.71 (64.201)

3. Secondary Outcome

Title	Sum of Time Weighted Differences From Baseline in Muscle Stiffness (SSID) With Movement Over the Interval
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Vehicle Topical Gel Vehicle: Vehicle Gel
Measure Participants	126	125
0-6 hours	-3.81 (6.218)	-3.33 (5.957)
6-12 hours	-7.75 (9.893)	-6.48 (8.796)
0-12 hours	-11.55 (15.446)	-9.81 (14.302)
12-24 hours	-17.20 (20.476)	-14.91 (19.369)
0-24 hours	-28.75 (34.920)	-24.72 (32.365)
24-36 hours	-23.33 (21.209)	-19.95 (22.555)
24-48 hours	-53.58 (44.528)	-44.77 (44.732)
0-36 hours	-52.08 (54.840)	-44.68 (53.031)
36-48 hours	-30.25 (23.947)	-24.82 (23.171)
0-48 hours	-82.33 (76.936)	-69.49 (73.804)

4. Secondary Outcome

Title	Total Relief With Movement (TOTPAR) 0-6 Hours Post Time Zero
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Vehicle Topical Gel Vehicle: Vehicle Gel
Measure Participants	126	125
Mean (Standard Deviation) [score on a scale*hours]	4.06 (3.435)	3.61 (3.978)

5. Secondary Outcome

Title	Subject Global Assessment of Study Medication Assessed at Approximately 48 Hours Post Time Zero
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Vehicle Topical Gel Vehicle: Vehicle Gel
Measure Participants	126	124
Original Categories - Poor	44 34.9%	50 40%
Original Categories - Fair	48 38.1%	47 37.6%
Original Categories - Good	25 19.8%	21 16.8%
Original Categories - Very good	9 7.1%	5 4%
Original Categories - Excellent	0 0%	1 0.8%
Dichotomized Categories - Poor/fair	92 73%	97 77.6%
Dichotomized Categories - Good/very good/excellent	34 27%	27 21.6%

6. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%	Vehicle Topical Gel Vehicle: Vehicle Gel
Measure Participants	126	125
Subjects with any TEAE	125 99.2%	121 96.8%
Subjects with any treatment-related TEAEs	124 98.4%	120 96%
Subjects with TEAEs leading to discontinuation	2 1.6%	2 1.6%
Subjects with SAEs	0 0%	0 0%
TEAE with mild in severity	119 94.4%	115 92%
TEAE with moderate in severity	6 4.8%	4 3.2%
TEAE with Severe in severity	0 0%	2 1.6%

Adverse Events

Time Frame	Up to Day 7
Adverse Event Reporting Description	TEAE was defined as an adverse event that was new or worsened in severity after the first dose of study drug.
Arm/Group Title	Active Arm		Placebo Arm
Arm/Group Description	S-Ibuprofen Topical Gel 5% S-Ibuprofen: Topical Gel 5%		Vehicle Topical Gel Vehicle: Vehicle Gel
All Cause Mortality
	Active Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/126 (0%)		0/125 (0%)
Serious Adverse Events
	Active Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/126 (0%)		0/125 (0%)
Other (Not Including Serious) Adverse Events
	Active Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	123/126 (97.6%)		117/125 (93.6%)
General disorders
application site erythema	123/126 (97.6%)		117/125 (93.6%)
application site induration	25/126 (19.8%)		21/125 (16.8%)
application site pain	70/126 (55.6%)		13/125 (10.4%)
application site pruritus	62/126 (49.2%)		76/125 (60.8%)
Musculoskeletal and connective tissue disorders
musculoskeletal stiffness	8/126 (6.3%)		8/125 (6.4%)
Skin and subcutaneous tissue disorders
skin exfoliation	27/126 (21.4%)		4/125 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.