Trial Outcomes & Findings for Iontophoresis With Dexamethasone and Physical Therapy to Treat Apophysitis of the Knee in Pediatrics (NCT NCT03606980)

Last Updated: 2024-03-06

Results Overview

The Return To Sport Criteria is met when all items on the Return To Sport Checklist can be successfully achieved. There are no units of measure for any of the criteria listed as they are either achieved/passed or not achieved/failed based on the criteria listed. Once all criteria can be passed, this date is noted. The number of days from Visit 1 to the date when all criteria are achieved is calculated. This outcome is measured in days.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

Measured at each Study Treatment Visit for a maximum of 12 Study Treatment Visits over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner

Results posted on

2024-03-06

Participant Flow

Participant milestones

Participant milestones
Measure	Iontophoresis With Dexamethasone Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee
Overall Study STARTED	16	15	14
Overall Study COMPLETED	12	13	7
Overall Study NOT COMPLETED	4	2	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Iontophoresis With Dexamethasone Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee
Overall Study Lost to Follow-up	3	2	3
Overall Study Withdrawal by Subject	1	0	4

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Iontophoresis With Dexamethasone n=16 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride n=15 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone n=14 Participants Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee	Total n=45 Participants Total of all reporting groups
Age, Categorical <=18 years	16 Participants n=16 Participants	15 Participants n=15 Participants	14 Participants n=14 Participants	45 Participants n=45 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=16 Participants	0 Participants n=15 Participants	0 Participants n=14 Participants	0 Participants n=45 Participants
Age, Categorical >=65 years	0 Participants n=16 Participants	0 Participants n=15 Participants	0 Participants n=14 Participants	0 Participants n=45 Participants
Sex: Female, Male Female	9 Participants n=16 Participants	4 Participants n=15 Participants	6 Participants n=14 Participants	19 Participants n=45 Participants
Sex: Female, Male Male	7 Participants n=16 Participants	11 Participants n=15 Participants	8 Participants n=14 Participants	26 Participants n=45 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Measured at each Study Treatment Visit for a maximum of 12 Study Treatment Visits over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner

Population: Analysis of return to sport time in patients who met return to sport criteria during study

Outcome measures

Outcome measures
Measure	Iontophoresis With Dexamethasone n=7 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride n=9 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone n=4 Participants Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee
Functional Outcome as Measured in Length of Time to Meet Return To Sport Criteria (Measured in Days)	38.1 days to meet return to sport criteria Standard Deviation 9.48	30.2 days to meet return to sport criteria Standard Deviation 6.8	37.25 days to meet return to sport criteria Standard Deviation 3.86

SECONDARY outcome

Timeframe: Collected at final visit, which is at Visit 12, maximum of 8 weeks, or when Return to Sport Criteria are met, whichever is sooner

Population: Analysis of final LEFS scores available across each group that completed full study participation. There were a total of 18 participants that did not complete their final LEFS scores across all three groups, so these patients have no final LEFS scores available for final analysis.

The LEFS is a patient reported questionnaire that measures difficult of completing 20 activities. The maximum possible score of the LEFS is 80 points, indicating very high function. The minimum possible score is 0 points, indicating very low function. The LEFS data is reported as a percentage, calculated as XX points/80 \* 100.

Outcome measures

Outcome measures
Measure	Iontophoresis With Dexamethasone n=8 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride n=11 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone n=8 Participants Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee
Patient Reported Outcome - Percent Difficulty With Activities as Measured by the Lower Extremity Function Scale (LEFS)	84.66 percent Standard Deviation 17.50	86.42 percent Standard Deviation 12.89	81.98 percent Standard Deviation 23.38

SECONDARY outcome

Timeframe: Measured at Study Treatment Visit 1 to establish baseline activity level (prior to onset of injury/pain)

Population: Analysis of initial Godin scores between groups

The Godin Leisure-Time Activity Questionnaire measures physical activity. Scores of 24 and above indicate the individual is "Active", scores of 14-23 indicate the individual is "Moderately Active", and scores of 14 and below indicate the individual is insufficiently active/sedentary. A higher score indicates higher levels of physical activity at baseline, thus would be considered a better outcome. The minimum possible score is 0, and there is no defined maximum score, as scores are based on patient's self-reported quantitative activity level, but scores of 24 and above indicate the highest levels of physical activity.

Outcome measures

Outcome measures
Measure	Iontophoresis With Dexamethasone n=16 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride n=15 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone n=14 Participants Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee
Patient Reported Outcome - Activity Level as Measured by the Godin Leisure-Time Activity Questionnaire	71.81 score on a scale Standard Deviation 23.61	58.07 score on a scale Standard Deviation 24.86	65.43 score on a scale Standard Deviation 18.54

SECONDARY outcome

Timeframe: Collected at final visit, which is at Visit 12, maximum of 8 weeks, or when Return to Sport Criteria are met, whichever is sooner

Population: Analysis of final FACES Pain scale ratings across all groups as available. We had 13 patients who did not provide final FACES pain data, thus that data was unable to be included in final analysis.

This scale was created for children to help them communicate their pain. The scale shows a series of faces ranging from a happy face at 0, "No hurt" to a crying face at 10 "Hurts worst".

Outcome measures

Outcome measures
Measure	Iontophoresis With Dexamethasone n=11 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride n=12 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone n=10 Participants Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee
Patient Reported Outcome - Pain as Measured by the Wong-Baker FACES Pain Rating Scale	1.33 score on a scale of 0-10 Standard Deviation 0.65	1.85 score on a scale of 0-10 Standard Deviation 1.07	2.13 score on a scale of 0-10 Standard Deviation 1.36

SECONDARY outcome

Timeframe: Measured at each Study Treatment Visit (up to 12 Study Treatment Visits over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner), then again 2 - 3 days, 30 days, and 90 days after Return To Sport Criteria are met.

Population: Participants in each group who experienced an AE

All adverse events that occur during participation in this research study, whether or not considered intervention-related, will be collected.

Outcome measures

Outcome measures
Measure	Iontophoresis With Dexamethasone n=14 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride n=10 Participants Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone n=9 Participants Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee
Number of Participants With Adverse Events Mild AE	8 Participants	5 Participants	4 Participants
Number of Participants With Adverse Events Moderate	4 Participants	5 Participants	5 Participants
Number of Participants With Adverse Events Severe	2 Participants	0 Participants	0 Participants

Adverse Events

Iontophoresis With Dexamethasone

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Iontophoresis With Sodium Chloride

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Physical Therapy Alone

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dana Reesman, PT, DPT

Children's Hospital of the King's Daughters

Phone: 757-668-4894

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Iontophoresis With Dexamethasone n=16 participants at risk Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of the dexamethasone sodium phosphate (4ml/1mL) will be placed on one side and 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Dexamethasone Sodium Phosphate: Dexamethasone sodium phosphate administered via iontophoresis Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Iontophoresis With Sodium Chloride n=15 participants at risk Iontophoresis is a non-invasive delivery mechanism for transmitting a medication to a local area of the body. The I-Bresis™ System and I-Bresis™ Patch will be the delivery system used for this study. The I-Bresis™ Patch is an adhesive patch. 1.5 ml of 0.9% sodium chloride (saline) solution will be placed on one side and 1.5 ml of 0.9% saline solution will be placed on the other. Duration of exposure: 123 minutes. Frequency of exposure: twice per week for a total of 12 sessions over a maximum of 8 weeks or until Return to Sport Criteria are met, whichever is sooner. Participants will also receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Iontophoresis: Iontophoresis on affected knee Physical Therapy: Physical therapy of affected knee	Physical Therapy Alone n=14 participants at risk Participants will only receive the standard PT protocol for apophysitis of the knee. This will involve up to 20 visits. Physical Therapy: Physical therapy of affected knee
Musculoskeletal and connective tissue disorders tibial tubercle hyperpigmentation	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders tibial tubercle pain	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders rolled ankle	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders small red bumps around tibia	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders redness superior to patch location	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders ankle sprain	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders anterior knee pain	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders foot/great toe pain	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders knee pain with flexion	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders shoulder pain	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders lesion	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Gastrointestinal disorders abdominal pain	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders abrasion	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders bilateral foot pain	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders bruised elbow	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Infections and infestations common cold	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Nervous system disorders concussion	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Gastrointestinal disorders constipation	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Gastrointestinal disorders diarrhea	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Respiratory, thoracic and mediastinal disorders dyspnea	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Ear and labyrinth disorders ear infection	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Infections and infestations influenza	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders fractured clavicle	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Nervous system disorders headache	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders left arm soreness	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Nervous system disorders migraine	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	7.1% 1/14 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Musculoskeletal and connective tissue disorders patellar tendinopathy	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders redness at patch site	12.5% 2/16 • Number of events 2 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders bruising around patch area	0.00% 0/16 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	6.7% 1/15 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders dryness over tibial tubercle	12.5% 2/16 • Number of events 2 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders pressure sensation under patch	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.
Skin and subcutaneous tissue disorders stinging	6.2% 1/16 • Number of events 1 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/15 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.	0.00% 0/14 • Adverse events were tracked throughout the study duration for each participant, i.e. approximately 5 months.