Trial Outcomes & Findings for A Study to Determine Safety and Efficacy of B244 in Subjects With Mild to Moderate Rosacea (NCT NCT03590366)

Last Updated: 2022-09-16

Results Overview

Safety and tolerability endpoints will consist of all treatment-related adverse events reporting during the study duration.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

140 participants

Primary outcome timeframe

Baseline to Day 84

Results posted on

2022-09-16

Participant Flow

Participant milestones

Participant milestones
Measure	B244 B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Overall Study STARTED	73	67
Overall Study COMPLETED	70	59
Overall Study NOT COMPLETED	3	8

Reasons for withdrawal

Reasons for withdrawal
Measure	B244 B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Overall Study Adverse Event	0	3
Overall Study Lost to Follow-up	3	3
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

A Study to Determine Safety and Efficacy of B244 in Subjects With Mild to Moderate Rosacea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	B244 n=73 Participants B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 Participants Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension	Total n=140 Participants Total of all reporting groups
Age, Continuous	50.6 years STANDARD_DEVIATION 15.099 • n=5 Participants	52.4 years STANDARD_DEVIATION 13.022 • n=7 Participants	51.5 years STANDARD_DEVIATION 14.120 • n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	48 Participants n=7 Participants	103 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=5 Participants	31 Participants n=7 Participants	62 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=5 Participants	36 Participants n=7 Participants	78 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	72 Participants n=5 Participants	65 Participants n=7 Participants	137 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 84

Population: Modified Intent to Treat (mITT) Population, which included all subjects who all subjects who met all inclusion/exclusion criteria, were randomized, dispensed treatment, and had at least one post-treatment efficacy evaluation.

Safety and tolerability endpoints will consist of all treatment-related adverse events reporting during the study duration.

Outcome measures

Outcome measures
Measure	B244 n=73 Participants B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 Participants Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	5 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline to Day 56

IGA (Investigator's Global Assessment) was used to assess the overall diseases severity on a scale of 0 to 4 (0=clear, 1=almost clear, 2=mild disease, 3=moderate disease, and 4=severe disease). Improvement is defined as at least 1-grade change.

Outcome measures

Outcome measures
Measure	B244 n=73 Participants B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 Participants Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Proportion of Subjects With IGA Improvement at Week 8 Relative to Baseline.	51 Participants	38 Participants

SECONDARY outcome

Timeframe: Baseline to Day 56

Clinical Erythema Assessment (CEA) was used to assess the extent of rosacea on a scale of 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). Improvement is defined as at least 1-grade change.

Outcome measures

Outcome measures
Measure	B244 n=73 Participants B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 Participants Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Proportion of Subjects With CEA Improvement at Week 8 Relative to Baseline.	49 Participants	38 Participants

SECONDARY outcome

Timeframe: Baseline to Day 56

Outcome measures

Outcome measures
Measure	B244 n=73 Participants B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 Participants Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Change in IGA From Week 8 to Baseline. Week 8 1-Grade Change	34 Participants	26 Participants
Change in IGA From Week 8 to Baseline. Week 8 2-Grade Change	14 Participants	10 Participants
Change in IGA From Week 8 to Baseline. Week 8 3-Grade Change	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline to Day 56

Clinical Erythema Assessment (CEA) was used to assess the extent of rosacea on a scale of 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). A higher grade change indicates greater improvement in disease.

Outcome measures

Outcome measures
Measure	B244 n=73 Participants B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 Participants Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Change in CEA From Week 8 to Baseline. Week 8 1-Grade Change	34 Participants	27 Participants
Change in CEA From Week 8 to Baseline. Week 8 2-Grade Change	14 Participants	10 Participants
Change in CEA From Week 8 to Baseline. Week 8 3-Grade Change	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline to Day 84

Population: Subjects from modified Intent to Treat (mITT) Population (all subjects who all subjects who met all inclusion/exclusion criteria, were randomized, dispensed treatment, and had at least one post-treatment efficacy evaluation) that remained in the study at each respective time point for the outcome measure.

The Skindex 16 questionnaire was assigned to subjects to examine the relationship between the subject's skin health and quality of life. Subjects scored 16 questions from 0 to 6 (0=never bothered, 6=always bothered). Total scores could range between 0 to 96, where a higher score is associated with a worse quality of life.

Outcome measures

Outcome measures
Measure	B244 n=73 Participants B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 Participants Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Change in Skindex 16 and Skindex 16 Sub Scores at Week 1, Week 4, Week 8 and Week 12 From Baseline. Change from Baseline at Week 12 (EOS)	-19.7 score on a scale Standard Deviation 22.152	-20.6 score on a scale Standard Deviation 22.694
Change in Skindex 16 and Skindex 16 Sub Scores at Week 1, Week 4, Week 8 and Week 12 From Baseline. Change from Baseline at Week 1	-8.7 score on a scale Standard Deviation 12.584	-12.4 score on a scale Standard Deviation 17.111
Change in Skindex 16 and Skindex 16 Sub Scores at Week 1, Week 4, Week 8 and Week 12 From Baseline. Change from Baseline at Week 4	-14.5 score on a scale Standard Deviation 13.908	-18.4 score on a scale Standard Deviation 17.418
Change in Skindex 16 and Skindex 16 Sub Scores at Week 1, Week 4, Week 8 and Week 12 From Baseline. Change from Baseline at Week 8	-21.0 score on a scale Standard Deviation 20.878	-19.9 score on a scale Standard Deviation 20.164

SECONDARY outcome

Timeframe: Baseline to Day 84

Subjects were asked to perform static ("snap-shot") evaluations of their rosacea-associated facial erythema severity using the Patient Self Assessment scale (PSA) at each study visit, and report the one integer that best describes the overall severity of their facial redness as seen in a mirror at the time of the evaluation on a scale of 0 to 4 (0=no redness, 1=very mild redness, 2=mild redness, 3=moderate redness, 4=severe redness). A higher grade change indicates greater improvement.

Outcome measures

Outcome measures
Measure	B244 n=73 Participants B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 Participants Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 1 · 0-Grade Change	49 Participants	44 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 1 · 1-Grade Change	19 Participants	19 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 1 · 2-Grade Change	5 Participants	3 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 1 · 3-Grade Change	0 Participants	0 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 4 · 0-Grade Change	29 Participants	23 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 4 · 1-Grade Change	36 Participants	30 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 4 · 2-Grade Change	5 Participants	6 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 4 · 3-Grade Change	1 Participants	0 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 8 · 0-Grade Change	23 Participants	21 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 8 · 2-Grade Change	14 Participants	11 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 8 · 3-Grade Change	3 Participants	3 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 12 (EOS) · 0-Grade Change	23 Participants	22 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 12 (EOS) · 1-Grade Change	29 Participants	21 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 12 (EOS) · 2-Grade Change	15 Participants	14 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 8 · 1-Grade Change	31 Participants	24 Participants
Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. Week 12 (EOS) · 3-Grade Change	3 Participants	2 Participants

Adverse Events

B244

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Vehicle

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Hyun Kim, Vice President Clinical Operations

AOBiome Therapeutics

Phone: 617-639-9980

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor shall have 60 days to review the papers. Sponsor shall have the right to require Institution/Principal Investigator, as applicable, to remove specifically identified confidential information and/or delay the proposed publication or presentation for an additional 90 days to enable Sponsor to seek patent protections.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	B244 n=73 participants at risk B244 suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. B244: B244 Suspension	Vehicle n=67 participants at risk Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. Vehicle: Vehicle suspension
Infections and infestations Hordeolum	2.7% 2/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Infections and infestations Urinary tract infection	2.7% 2/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Infections and infestations Viral upper respiratory tract infection	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Infections and infestations Acute sinusitis	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Infections and infestations Eye infection	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Infections and infestations Gastroenteritis	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Infections and infestations Oral herpes	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Infections and infestations Sinusitis	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Infections and infestations Upper respiratory tract infection	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Skin and subcutaneous tissue disorders Pruritus	4.1% 3/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Skin and subcutaneous tissue disorders Rash	2.7% 2/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Skin and subcutaneous tissue disorders Erythema	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Skin and subcutaneous tissue disorders Acne	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Skin and subcutaneous tissue disorders Skin discolouration	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
General disorders Application site pain	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	4.5% 3/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
General disorders Application site dryness	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	3.0% 2/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
General disorders Application site pruritus	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	3.0% 2/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
General disorders Application site erythema	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
General disorders Application site plaque	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
General disorders Oedema peripheral	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Nervous system disorders Headache	2.7% 2/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Nervous system disorders Paraesthesia	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Nervous system disorders Sciatica	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Gastrointestinal disorders Breath odour	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Immune system disorders Dermatitis contact	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Immune system disorders Seasonal allergy	0.00% 0/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	1.5% 1/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Eye disorders Lacrimation increased	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Injury, poisoning and procedural complications Fall	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Injury, poisoning and procedural complications Limb injury	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Investigations Alanine aminotransferase increased	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Investigations Aspartate aminotransferase increased	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Renal and urinary disorders Dysuria	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.4% 1/73 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.	0.00% 0/67 • Baseline to Week 12. Beginning with the Screening visit and through the end of study or early termination (ET) visit, the PI and study personnel reviewed each subject's clinical evaluation findings and queried the subject directly regarding AEs. Subjects were to be followed for AEs until 30 days post study conclusion or until the PI determined the AEs were stable, whichever was later. PIs monitored each subject for clinical evidence of adverse events on a routine basis throughout the study.