The IGA score was determined according to the 5 point scale below.

0=Clear skin with no inflammatory and non-inflammatory lesions

1. Almost clear; rare non-inflammatory lesions with no more than one small inflammatory lesion
2. Mild severity; greater than Grade 1; some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions)
3. Moderate severity; greater than Grade 2; up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesions
4. Severe; greater than Grade 3; up to many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions

The Local Skin Responses consists of the following 6 components: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR component is given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity. The composite LSR score (0-24) is the sum of the scores graded from 0 to 4 on all six individual LSR categories.

Please see following outcome measure descriptions on the grading scale for the individual components:

• Erosion/ulceration: 6. Secondary outcome measure
• Crusting: 7. Secondary outcome measure.
• Erythema: 8. Secondary outcome measure.
• Flaking/scaling: 9. Secondary outcome measure.
• Swelling: 10. Secondary outcome measure.
• Vesiculation/pustulation: 11. Secondary outcome measure.

The Erosion/Ulceration score was determined according to the 5 point scale below.

0=not present

1. Lesion specific erosion
2. Erosion extending beyond individual lesions
3. Erosion >50%
4. Black eschar or ulceration

The crusting score was determined according to the 5 point scale below.

0=not present

1. isolated crusting
2. Crusting<50%
3. Crusting>50%
4. Crusting extending outside treatment area

The erythema score was determined according to the 5 point scale below. Erythema 0=not present

1. slightly pink <50%
2. Pink or light red >50%
3. Red,restricted to treatment area
4. Red extending outside treatment area

The flaking/scaling score was determined according to the 5 point scale below. 0=not present

1. Isolated scale, specific to lesion
2. Scale<50%
3. Scale>50%
4. Scaling extending outside treatment area

The swelling score was determined according to the 5 point scale below. 0=Not present

1. Slight, lesion specific oedema
2. Palpable oedema extending beyond individual lesions
3. Confluent and/or visible oedema
4. Marked swelling extending outside treatment area

The vesiculation/postulation score was determined according to the 5 point scale below.

0=not present

1. vesicles only
2. Transudate or pustulates with or without vesicles <50%
3. Transudate or pustulates, with or without vesicles >50%
4. Transudate or pustulates, with or without vesicles extending outside treatment area

4=Marked swelling extending outside treatment area

Unacceptable LSRs, safety and tolerability in an individual participant were defined as:

1. Clinically relevant signs or symptoms that in the opinion of the investigator were deemed unacceptable.
2. Occurrence of LSRs as specified below:

One of the following

• Grade 4 crusting
• Grade 4 erosion/ulceration
• Grade 4 vesiculation/pustulation extending significantly outside treatment areas

Two of the following

• Grade 4 erythema
• Grade 3 crusting
• Grade 4 swelling extending significantly outside treatment areas
• Grade 3 erosion/ulceration
• Grade 3 vesiculation/pustulation

Count of inflammatory lesions in acne lesion areas

The analysis was based on the full analysis set (FAS). The FAS consisted of all participants except the first 2 participants included in Cohort 1 (according to protocol) were included in the FAS, thus the FAS comprised 38 participants. At Week 12, FAS comprised 32 participants as 6 participants discontinued before Week 12.

Count of non-inflammatory lesions in acne lesion areas

The analysis was based on the full analysis set (FAS). The FAS consisted of all participants except the first 2 participants included in Cohort 1 (according to protocol) were included in the FAS, thus the FAS comprised 38 participants. At Week 12, FAS comprised 32 participants as 6 participants discontinued before Week 12.

The IGA score was determined according to the 5 point scale below.

0=Clear skin with no inflammatory and non-inflammatory lesions

1. Almost clear; rare non-inflammatory lesions with no more than one small inflammatory lesion
2. Mild severity; greater than Grade 1; some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions)
3. Moderate severity; greater than Grade 2; up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesions
4. Severe; greater than Grade 3; up to many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions

The analysis was based on the full analysis set (FAS). The FAS consisted of all participants except the first 2 participants included in Cohort 1 (according to protocol) were included in the FAS, thus the FAS comprised 38 participants. At Week 12, FAS comprised 32 participants as 6 participants discontinued before Week 12.

The Local Skin Responses consists of the following 6 components: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR component is given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity. The composite LSR score (0-24) is the sum of the scores graded from 0 to 4 on all six individual LSR categories.

Please see following outcome measure descriptions on the grading scale for the individual components:

• Erosion/ulceration: 6. Secondary outcome measure
• Crusting: 7. Secondary outcome measure.
• Erythema: 8. Secondary outcome measure.
• Flaking/scaling: 9. Secondary outcome measure.
• Swelling: 10. Secondary outcome measure.
• Vesiculation/pustulation: 11. Secondary outcome measure.

6 participants did not complete the trial and 7 participants had one or more missing visits during the trial.

The Erosion/Ulceration score was determined according to the 5 point scale below.

0=not present

1. Lesion specific erosion
2. Erosion extending beyond individual lesions
3. Erosion >50%
4. Black eschar or ulceration

6 participants did not complete the trial and 7 participants had one or more missing visits during the trial.

The crusting score was determined according to the 5 point scale below.

0=not present

1. isolated crusting
2. Crusting<50%
3. Crusting>50%
4. Crusting extending outside treatment area

6 participants did not complete the trial and 7 participants had one or more missing visits during the trial.

The erythema score was determined according to the 5 point scale below. Erythema 0=not present

1. slightly pink <50%
2. Pink or light red >50%
3. Red,restricted to treatment area
4. Red extending outside treatment area

6 participants did not complete the trial and 7 participants had one or more missing visits during the trial.

The flaking/scaling score was determined according to the 5 point scale below. 0=not present

1. Isolated scale, specific to lesion
2. Scale<50%
3. Scale>50%
4. Scaling extending outside treatment area

6 participants did not complete the trial and 7 participants had one or more missing visits during the trial.

The swelling score was determined according to the 5 point scale below. 0=Not present

1. Slight, lesion specific oedema
2. Palpable oedema extending beyond individual lesions
3. Confluent and/or visible oedema
4. Marked swelling extending outside treatment area

6 participants did not complete the trial and 7 participants had one or more missing visits during the trial.

The vesiculation/postulation score was determined according to the 5 point scale below.

0=not present

1. vesicles only
2. Transudate or pustulates with or without vesicles <50%
3. Transudate or pustulates, with or without vesicles >50%
4. Transudate or pustulates, with or without vesicles extending outside treatment area

4=Marked swelling extending outside treatment area

6 participants did not complete the trial and 7 participants had one or more missing visits during the trial.

Unacceptable LSRs, safety and tolerability in an individual participant were defined as:

1. Clinically relevant signs or symptoms that in the opinion of the investigator were deemed unacceptable.
2. Occurrence of LSRs as specified below:

One of the following

• Grade 4 crusting
• Grade 4 erosion/ulceration
• Grade 4 vesiculation/pustulation extending significantly outside treatment areas

Two of the following

• Grade 4 erythema
• Grade 3 crusting
• Grade 4 swelling extending significantly outside treatment areas
• Grade 3 erosion/ulceration
• Grade 3 vesiculation/pustulation

LEO 43204 0.018% gel administered to an acne lesion on either left or right cheek

LEO 43204 vehicle gel administered to an acne lesion on either left or right cheek