Trial Outcomes & Findings for Study to Evaluate Safety and Tolerability of BF-200 ALA (Ameluz®) for Photodynamic Therapy in the Treatment of the Expanded Field of Actinic Keratosis on Face and Scalp (NCT NCT05060237)

NCT ID: NCT05060237

Last Updated: 2024-10-17

Results Overview

Assessed by the subjects using an 11-point numeric rating scale (NRS), where a score of 0 means "no pain" and a score of 10 means "worst imaginable pain".

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 112 participants
• Primary outcome timeframe: At treatment day (day 1, Visit 2) after end of illumination
• Results posted on: 2024-10-17

Participant Flow

According to protocol, 100 participants were planned to be dosed. To meet this requirement, 112 participants were enrolled, resulting in 100 participants to receive treatment.

Participant milestones

Measure	BF-200 ALA Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²), followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Overall Study STARTED	112
Overall Study Treated on the Face	40
Overall Study Treated on the Scalp	39
Overall Study Treated on the Face and Scalp	21
Overall Study COMPLETED	100
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Measure	BF-200 ALA Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²), followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Overall Study Withdrawal by Subject	4
Overall Study Screening failure	8

Baseline Characteristics

Study to Evaluate Safety and Tolerability of BF-200 ALA (Ameluz®) for Photodynamic Therapy in the Treatment of the Expanded Field of Actinic Keratosis on Face and Scalp

Baseline characteristics by cohort

Measure	Face (BF-200 ALA) n=40 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.	Scalp (BF-200 ALA) n=39 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.	Face and Scalp (BF-200 ALA) n=21 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.	Total n=100 Participants Total of all reporting groups
Age, Continuous	66.5 years STANDARD_DEVIATION 7.5 • n=5 Participants	70.1 years STANDARD_DEVIATION 6.7 • n=7 Participants	66.5 years STANDARD_DEVIATION 7.9 • n=5 Participants	67.9 years STANDARD_DEVIATION 7.4 • n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	39 Participants n=7 Participants	21 Participants n=5 Participants	88 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants	38 Participants n=7 Participants	21 Participants n=5 Participants	99 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	40 Participants n=5 Participants	39 Participants n=7 Participants	20 Participants n=5 Participants	99 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Fitzpatrick skin type I-II	31 Participants n=5 Participants	20 Participants n=7 Participants	14 Participants n=5 Participants	65 Participants n=4 Participants
Fitzpatrick skin type III-IV	9 Participants n=5 Participants	19 Participants n=7 Participants	7 Participants n=5 Participants	35 Participants n=4 Participants
Number of AK lesions Total	17.6 Number of AK lesions STANDARD_DEVIATION 11.0 • n=5 Participants	15.7 Number of AK lesions STANDARD_DEVIATION 11.3 • n=7 Participants	16.8 Number of AK lesions STANDARD_DEVIATION 11.4 • n=5 Participants	16.7 Number of AK lesions STANDARD_DEVIATION 11.1 • n=4 Participants
Number of AK lesions Diameter < 4 mm	4.3 Number of AK lesions STANDARD_DEVIATION 9.9 • n=5 Participants	4.1 Number of AK lesions STANDARD_DEVIATION 10.1 • n=7 Participants	1.8 Number of AK lesions STANDARD_DEVIATION 3.9 • n=5 Participants	3.7 Number of AK lesions STANDARD_DEVIATION 9.1 • n=4 Participants
Number of AK lesions Diameter ≥ 4 mm	13.3 Number of AK lesions STANDARD_DEVIATION 7.9 • n=5 Participants	11.6 Number of AK lesions STANDARD_DEVIATION 4.4 • n=7 Participants	15.0 Number of AK lesions STANDARD_DEVIATION 11.4 • n=5 Participants	13.0 Number of AK lesions STANDARD_DEVIATION 7.8 • n=4 Participants
Total area of AK target lesions ≥ 4 mm	426.5 mm ^2 STANDARD_DEVIATION 269.7 • n=5 Participants	701.8 mm ^2 STANDARD_DEVIATION 830.6 • n=7 Participants	626.8 mm ^2 STANDARD_DEVIATION 361.0 • n=5 Participants	575.9 mm ^2 STANDARD_DEVIATION 579.3 • n=4 Participants
Severity of AK target lesions ≥ 4 mm Mild/ grade 1	329 Number of AK lesions n=5 Participants	209 Number of AK lesions n=7 Participants	147 Number of AK lesions n=5 Participants	685 Number of AK lesions n=4 Participants
Severity of AK target lesions ≥ 4 mm Moderate/ grade 2	203 Number of AK lesions n=5 Participants	231 Number of AK lesions n=7 Participants	165 Number of AK lesions n=5 Participants	599 Number of AK lesions n=4 Participants
Severity of AK target lesions ≥ 4 mm Severe/ grade 3	0 Number of AK lesions n=5 Participants	12 Number of AK lesions n=7 Participants	3 Number of AK lesions n=5 Participants	15 Number of AK lesions n=4 Participants

PRIMARY outcome

Timeframe: Through study completion, on average 6 weeks

TEAEs are defined as all AEs with onset or worsening after treatment with IMP up to Visit 5 (Final Visit). TEAEs are considered being related to IMP or medical device, if causal relationship between IMP or medical device and the TEAE is at least possible or relationship assessment is missing. If an AE occurs in different treatment areas (face, scalp, face and scalp), it is reported separately for each treatment area. Thus, some AEs are counted more than once.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any AEs	888 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any AEs : mild	563 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any AEs : moderate	242 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any AEs : severe	83 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any serious AEs	0 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs	871 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs : mild	546 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs : moderate	242 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs : severe	83 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any serious TEAEs	0 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs leading to death	0 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs related to IMP	809 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs related to medical device	782 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs related to IMP or medical device	811 Number of events
Frequency and Severity of Adverse Events (AEs), Serious AEs (SAEs), and Treatment Emergent Adverse Events (TEAEs). Any TEAEs leading to study discontinuation	0 Number of events

PRIMARY outcome

Timeframe: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)

The duration of TEAEs related to IMP and/or medical device which occurred in at least two subjects and with complete start and stop dates was analyzed. In addition, the proportion of the duration by severity was analyzed. Duration of severity per subject and preferred term is calculated in days counting all days and all episodes of one severity category together. Calculation is done referring to all subjects with occurrence of respective preferred term. If a severity category of a preferred term does not occur in a subject, the duration of this category is set to 0. If an AE occurs in different treatment areas, it is reported separately for each treatment area (face, scalp, face and scalp). Thus, some AEs are counted more than once for the analysis.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site discharge : all severities	5.50 days Standard Deviation 3.32
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site discharge : mild	5.50 days Standard Deviation 3.32
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site discolouration : all severities	11.17 days Standard Deviation 5.60
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site discolouration : mild	4.33 days Standard Deviation 4.97
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site discolouration : moderate	6.83 days Standard Deviation 8.82
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site discomfort : all severities	4.55 days Standard Deviation 2.84
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site discomfort : mild	4.55 days Standard Deviation 2.84
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site dryness : all severities	12.33 days Standard Deviation 10.02
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site dryness : mild	8.00 days Standard Deviation 12.17
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site dryness : moderate	4.33 days Standard Deviation 7.51
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site erosion : all severities	8.88 days Standard Deviation 5.07
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site erosion : mild	5.59 days Standard Deviation 4.78
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site erosion : moderate	2.81 days Standard Deviation 5.37
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site induration : all severities	15.71 days Standard Deviation 29.67
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site induration : mild	12.41 days Standard Deviation 30.72
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site induration : moderate	3.29 days Standard Deviation 4.86
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site oedema : all severities	9.76 days Standard Deviation 4.97
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site oedema : mild	6.93 days Standard Deviation 5.80
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site oedema : moderate	2.69 days Standard Deviation 3.78
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site oedema : severe	0.15 days Standard Deviation 0.86
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pain : all severities	8.91 days Standard Deviation 7.11
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pain : mild	4.19 days Standard Deviation 6.17
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pain : moderate	2.84 days Standard Deviation 4.99
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pain : severe	1.87 days Standard Deviation 3.47
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site papules : all severities	8.50 days Standard Deviation 4.95
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site papules : mild	8.50 days Standard Deviation 4.95
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site paraesthesia : all severities	3.00 days Standard Deviation 2.39
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site paraesthesia : mild	2.13 days Standard Deviation 2.29
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site paraesthesia : moderate	0.47 days Standard Deviation 0.83
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site paraesthesia : severe	0.40 days Standard Deviation 1.55
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pruritus : all severities	9.29 days Standard Deviation 7.30
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pruritus : mild	8.06 days Standard Deviation 7.42
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pruritus : moderate	1.13 days Standard Deviation 3.64
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pruritus : severe	0.10 days Standard Deviation 0.60
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pustules : all severities	5.67 days Standard Deviation 1.53
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pustules : mild	3.83 days Standard Deviation 2.84
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site pustules : moderate	1.83 days Standard Deviation 1.61
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site scab : all severities	10.81 days Standard Deviation 7.42
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site scab : mild	7.53 days Standard Deviation 8.52
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site scab : moderate	3.17 days Standard Deviation 4.83
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site scab : severe	0.11 days Standard Deviation 0.79
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site swelling : all severities	6.50 days Standard Deviation 3.33
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site swelling : mild	5.83 days Standard Deviation 4.22
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site swelling : moderate	0.67 days Standard Deviation 1.63
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site vesicles : all severities	5.07 days Standard Deviation 4.08
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site vesicles : mild	4.68 days Standard Deviation 4.00
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site vesicles : moderate	0.39 days Standard Deviation 1.00
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site warmth : all severities	2.13 days Standard Deviation 1.75
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site warmth : mild	0.72 days Standard Deviation 0.97
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site warmth : moderate	0.94 days Standard Deviation 1.06
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site warmth : severe	0.47 days Standard Deviation 1.12
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Blood pressure increased : all severities	5.50 days Standard Deviation 2.12
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Blood pressure increased : mild	3.50 days Standard Deviation 4.95
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Blood pressure increased : moderate	2.00 days Standard Deviation 2.83
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Chills : all severities	1.60 days Standard Deviation 0.89
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Chills : mild	1.20 days Standard Deviation 0.45
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Chills : moderate	0.40 days Standard Deviation 0.89
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Dry Eye : all severities	5.00 days Standard Deviation 2.65
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Dry Eye : mild	5.00 days Standard Deviation 2.65
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Fatigue : all severities	4.50 days Standard Deviation 1.29
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Fatigue : mild	2.25 days Standard Deviation 2.87
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Fatigue : moderate	2.25 days Standard Deviation 2.63
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Headache : all severities	2.71 days Standard Deviation 1.79
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Headache : mild	2.15 days Standard Deviation 2.12
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Headache : moderate	0.56 days Standard Deviation 0.90
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Nausea : all severities	1.00 days Standard Deviation 0.00
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Nausea : mild	0.50 days Standard Deviation 0.71
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Nausea : moderate	0.50 days Standard Deviation 0.71
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Poor quality sleep : all severities	7.50 days Standard Deviation 0.71
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Poor quality sleep : mild	4.00 days Standard Deviation 5.66
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Poor quality sleep : moderate	3.50 days Standard Deviation 4.95
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site erosion : severe	0.47 days Standard Deviation 1.88
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site erythema : all severities	19.04 days Standard Deviation 12.78
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site erythema : mild	10.09 days Standard Deviation 13.60
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site erythema : moderate	7.95 days Standard Deviation 10.11
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site erythema : severe	1.00 days Standard Deviation 4.80
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site exfoliation : all severities	13.62 days Standard Deviation 9.81
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site exfoliation : mild	10.48 days Standard Deviation 8.65
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site exfoliation : moderate	2.79 days Standard Deviation 6.16
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site exfoliation : severe	0.35 days Standard Deviation 1.46
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site haemorrhage : all severities	3.33 days Standard Deviation 2.74
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site haemorrhage : mild	2.28 days Standard Deviation 2.31
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site haemorrhage : moderate	1.06 days Standard Deviation 2.65
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site hyperaesthesia : all severities	6.22 days Standard Deviation 3.27
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site hyperaesthesia : mild	3.61 days Standard Deviation 2.69
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site hyperaesthesia : moderate	2.44 days Standard Deviation 4.45
Duration of TEAEs Including the Breakdown of Severity Category (Mild, Moderate, Severe). Application site hyperaesthesia : severe	0.17 days Standard Deviation 0.50

PRIMARY outcome

Timeframe: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)

Assessed were newly occuring lesions of actinic keratosis (AK), non-melanoma skin cancer (NMSC) such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or Bowens disease, and melanoma inside the treatment field. Cumulative number of lesions is reported.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field Any new lesions	38 Number of lesions
Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field Seborrhoeic keratosis	1 Number of lesions
Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field Actinic keratosis	36 Number of lesions
Assessment of New Lesions (AK, NMSC Such as BCC, SCC or Bowens Disease, and Melanoma) if They Occur Inside the Treatment Field Milia	1 Number of lesions

PRIMARY outcome

Timeframe: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)

Assessed were newly occuring lesions of actinic keratosis (AK), non-melanoma skin cancer (NMSC) such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or Bowens disease, and melanoma inside the treatment field. Cumulative number of lesions is reported.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm Any new lesions	10 Number of lesions
Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm Seborrhoeic keratosis	1 Number of lesions
Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm Squamous cell carcinoma	1 Number of lesions
Assessment of New Lesions (AK, NMSC, and Melanoma) if They Occur Around the Treatment Field at a Distance of <10 cm Actinic keratosis	8 Number of lesions

PRIMARY outcome

Timeframe: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)

Application site skin reaction categories: discharge, erosion, erythema, exfoliation, fissure, induration, oedema, scabbing, skin flaking, ulceration, vesicles, other; severity of AE: mild, moderate or severe

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Any application site skin reactions	96.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site discharge	4.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site discolouration	6.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site dryness	4.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site erosion	16.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site erythema	86.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site exfoliation	87.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site fissure	1.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site haemorrhage	10.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site induration	18.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site oedema	35.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site papules	2.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site scab	49.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site swelling	6.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site vesicles	14.0 percentage of partcipants
Application Site Skin Reactions During and Post PDT, Assessed by the Investigator Application site pustules	3.0 percentage of partcipants

PRIMARY outcome

Timeframe: From treatment day (day 1, Visit 2) up to Visit 5 (approx. 28 days post treatment)

Application site discomfort categories: burning, hyperaesthesia, pain, paraesthesia, pruritus, stinging, warmth, other; severity of AE: mild, moderate or severe

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Application Site Discomfort During and Post PDT, Reported by the Subjects Any application site discomfort	97.0 percentage of participants
Application Site Discomfort During and Post PDT, Reported by the Subjects Application site discomfort	11.0 percentage of participants
Application Site Discomfort During and Post PDT, Reported by the Subjects Application site hyperaesthesia	10.0 percentage of participants
Application Site Discomfort During and Post PDT, Reported by the Subjects Application site hypoaesthesia	1.0 percentage of participants
Application Site Discomfort During and Post PDT, Reported by the Subjects Application site pain	96.0 percentage of participants
Application Site Discomfort During and Post PDT, Reported by the Subjects Application site paraesthesia	15.0 percentage of participants
Application Site Discomfort During and Post PDT, Reported by the Subjects Application site photosensitivity reaction	1.0 percentage of participants
Application Site Discomfort During and Post PDT, Reported by the Subjects Application site pruritus	65.0 percentage of participants
Application Site Discomfort During and Post PDT, Reported by the Subjects Application site warmth	17.0 percentage of participants

PRIMARY outcome

Timeframe: At treatment day (day 1, Visit 2) after end of illumination

Population: For this study, concomitant medication as pain-relieving measure prior to illumination, concomitant medications given as pain-relieving measures during illumination and physical pain-relieving measures (i.e. interruption of the illumination and/or cooling with an air stream and/or nebulized water) were allowed. Subjects might have received a combination of medications (prior and/or during) and/or measures.

Assessed by the subjects using an 11-point numeric rating scale (NRS), where a score of 0 means "no pain" and a score of 10 means "worst imaginable pain".

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Application Site Pain During Illumination Overall	7.4 score on a scale Standard Deviation 2.1
Application Site Pain During Illumination Without concomitant pain relieving medication prior to illumination	7.6 score on a scale Standard Deviation 1.8
Application Site Pain During Illumination With concomitant pain relieving medication prior to illumination	7.2 score on a scale Standard Deviation 2.5
Application Site Pain During Illumination Without concomitant pain relieving medication during illumination	7.3 score on a scale Standard Deviation 2.1
Application Site Pain During Illumination With concomitant pain relieving medication during illumination	8.4 score on a scale Standard Deviation 1.9
Application Site Pain During Illumination Without physical pain relieving measures during illumination	8.1 score on a scale Standard Deviation 2.0
Application Site Pain During Illumination With physical pain relieving measures during illumination	7.3 score on a scale Standard Deviation 2.2

PRIMARY outcome

Timeframe: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment

Population: One subject had elevated systolic and diastolic blood pressure at Visit 1 which was considered clinically significant and thus documented as relevant medical history. At Visit 2, blood pressure data was missing for one subject for the timepoint 'within 10 min prior to illumination', and for two subjects for the timepoint '60 min after illumination'. One subject missed Visit 3 and thus had no vital sign measurements at Visit 3.

Change from baseline is presented. The first measurement at Visit 2 (arrival at site) was considered as baseline value for all following measurements. Blood pressure was measured in mmHg. At Visit 2, photodynamic therapy was performed.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Changes in Blood Pressure (Systolic and Diastolic) Diastolic blood pressure - Visit 2 : 60 min after illumination	4.4 mmHg Standard Deviation 7.9
Changes in Blood Pressure (Systolic and Diastolic) Systolic blood pressure - Visit 2 : Within 10 min before illumination	5.7 mmHg Standard Deviation 12.8
Changes in Blood Pressure (Systolic and Diastolic) Systolic blood pressure - Visit 2 : Within 10 min after illumination	17.3 mmHg Standard Deviation 16.5
Changes in Blood Pressure (Systolic and Diastolic) Systolic blood pressure - Visit 2 : 60 min after illumination	10.8 mmHg Standard Deviation 15.0
Changes in Blood Pressure (Systolic and Diastolic) Systolic blood pressure - Visit 3	1.1 mmHg Standard Deviation 12.5
Changes in Blood Pressure (Systolic and Diastolic) Systolic blood pressure - Visit 4	-1.1 mmHg Standard Deviation 13.4
Changes in Blood Pressure (Systolic and Diastolic) Systolic blood pressure - Visit 5	-0.9 mmHg Standard Deviation 14.5
Changes in Blood Pressure (Systolic and Diastolic) Diastolic blood pressure - Visit 2 : Within 10 min before illumination	2.3 mmHg Standard Deviation 6.6
Changes in Blood Pressure (Systolic and Diastolic) Diastolic blood pressure - Visit 2 : Within 10 min after illumination	7.1 mmHg Standard Deviation 9.3
Changes in Blood Pressure (Systolic and Diastolic) Diastolic blood pressure - Visit 3	1.0 mmHg Standard Deviation 8.8
Changes in Blood Pressure (Systolic and Diastolic) Diastolic blood pressure - Visit 4	-0.6 mmHg Standard Deviation 8.3
Changes in Blood Pressure (Systolic and Diastolic) Diastolic blood pressure - Visit 5	0.8 mmHg Standard Deviation 8.5

PRIMARY outcome

Timeframe: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment

Population: At Visit 2, pulse rate data was missing for one subject for the timepoint 'within 10 min prior to illumination', and for two subjects for the timepoint '60 min after illumination'. One subject missed Visit 3 and thus had no vital sign measurements at Visit 3.

Change from baseline is presented. The first measurement at Visit 2 (arrival at the site) was considered as baseline value for all following measurements. Pulse rate was measures in beats/min. At Visit 2, photodynamic therapy was performed.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Changes in Pulse Rate Visit 2 : Within 10 min prior to illumination	-2.1 beats per min Standard Deviation 10.0
Changes in Pulse Rate Visit 2 : Within 10 min after illumination	-1.2 beats per min Standard Deviation 10.2
Changes in Pulse Rate Visit 2 : 60 min after illumination	-2.8 beats per min Standard Deviation 9.5
Changes in Pulse Rate Visit 3	0.7 beats per min Standard Deviation 9.8
Changes in Pulse Rate Visit 4	0.7 beats per min Standard Deviation 10.0
Changes in Pulse Rate Visit 5	1.0 beats per min Standard Deviation 9.2

PRIMARY outcome

Timeframe: All visits through study completion after Visit 1: Visit 2, baseline, treatment day; Visit 3, approx. 7 days post treatment; Visit 4, approx.14 days post treatment; Visit 5, approx. 28 days post treatment

Population: At Visit 2, body temperature data was missing for one subject for the timepoint 'within 10 min prior to illumination', and for three subjects for the timepoint '60 min after illumination'. One subject missed Visit 3 and thus had no vital sign measurement at Visit 3. For one other subject, no temperature data was available at Visit 3.

Change from baseline is presented. The first measurement at Visit 2 (arrival at site) was considered as baseline value for all following measurements. Body temperature was measured in °F and was converted to °C in the electronic Case Report Form. At Visit 2, photodynamic therapy was performed.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Changes in Body Temperature Visit 2 : Within 10 min prior to illumination	-0.11 °C Standard Deviation 0.41
Changes in Body Temperature Visit 2 : Within 10 min after illumination	-0.17 °C Standard Deviation 0.60
Changes in Body Temperature Visit 2 : 60 min after illumination	-0.08 °C Standard Deviation 0.43
Changes in Body Temperature Visit 3	0.04 °C Standard Deviation 0.40
Changes in Body Temperature Visit 4	-0.05 °C Standard Deviation 0.39
Changes in Body Temperature Visit 5	-0.03 °C Standard Deviation 0.39

PRIMARY outcome

Timeframe: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)

Population: Visit 1: For one subject, clinical chemistry but no hematology parameters were analyzed, as the sample arrived at the analyzing laboratory too late. However, no clinical chemistry measurements were documented for this subject. One other subject had no blood sample collected at Visit 1. Visit 5: One subject had no hematology and clinical chemistry assessment at Visit 5, as the blood sample was inadvertently not collected.

Findings which differ from reference range and are considered to be clinically significant are to be reported. Clinical chemistry parameters include glucose, creatinine, total bilirubin, aspartate aminotransferase (AST), alanineaminotransferase (ALT), lactate dehydrogenase (LDH), alkalinephosphatase (AP),gamma glutamyl transferase (GGT), potassium, sodium, calcium, total protein, albumin.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Investigation of Clinical Chemistry Parameters Visit 1 (Overall)	1 participants with findings considered CS
Investigation of Clinical Chemistry Parameters Visit 1 - elevated blood glucose	1 participants with findings considered CS
Investigation of Clinical Chemistry Parameters Visit 5 (Overall)	2 participants with findings considered CS
Investigation of Clinical Chemistry Parameters Visit 5 - elevated alanine aminotransferase	1 participants with findings considered CS
Investigation of Clinical Chemistry Parameters Visit 5 - elevated aspartate aminotransferase	1 participants with findings considered CS
Investigation of Clinical Chemistry Parameters Visit 5 - elevated gamma glutamyl transferase	2 participants with findings considered CS
Investigation of Clinical Chemistry Parameters Visit 5 - elevated blood glucose	1 participants with findings considered CS

PRIMARY outcome

Timeframe: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)

Population: Visit 1: For one subject, clinical chemistry but no hematology parameters were analyzed, as the sample arrived at the analyzing laboratory too late. However, no clinical chemistry measurements were documented for this subject. One other subject had no blood sample collected at Visit 1. Visit 5: One subject had no hematology and clinical chemistry assessment at Visit 5, as the blood sample was inadvertently not collected.

Findings which differ from reference range and are considered to be clinically significant are to be reported. Hematology parameters include hemoglobin, hematocrit, red blood cell count, leukocyte count (white blood cells(WBC)) with differential count (neutrophils, lymphocytes, monocytes, eosinophils, basophils), and platelet count.

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Investigation of Hematology Parameters Visit 1	0 participants with findings considered CS
Investigation of Hematology Parameters Visit 5	0 participants with findings considered CS

PRIMARY outcome

Timeframe: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)

Population: Reasons for missing urinalysis data for 3 subjects at Visit 5 were "study coordinator error" (n=2) and "urinalysis inadvertently not collected" (n=1).

Findings which differ from reference range and are considered to be clinically significant (CS) are to be reported

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Investigation of Urinalysis Parameters Visit 1	0 participants with findings considered CS
Investigation of Urinalysis Parameters Visit 5	0 participants with findings considered CS

PRIMARY outcome

Timeframe: At screening (Visit 1, up to 14 days before treatment) and at Visit 5 (approx. 28 days post treatment)

Population: At Visit 1, one participant had findings considered clinically significant. Of this 1 participant, these findings concerned the nervous system.

Abnormal findings, considered to be clinically significant (CS), are to be reported

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status Visit 1	1 participants with findings considered CS
Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status Of these: Findings concerning the nervous system	1 participants with findings considered CS
Physical Examination of Head, Neck, Skin, Lymph Nodes, Thorax Including Heart and Lungs, Abdomen, and Musculoskeletal, Peripheral Vascular and Nervous System Status Visit 5	0 participants with findings considered CS

PRIMARY outcome

Timeframe: At screening (Visit 1, up to 14 days before treatment) and at Visit 2 (treatment day 1)

Population: Four subjects had missing data at Visit 1.

Including picture- and question-based memory tasks; abnormal findings that are considered clinically significant will be documented

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Memory Tests Visit 1 - All pictures memorized correctly · No answer	0 Participants
Memory Tests Visit 1 - All pictures memorized correctly · Yes	96 Participants
Memory Tests Visit 1 - All pictures memorized correctly · No	0 Participants
Memory Tests Visit 1 - Questions on personal identification answered correctly · No answer	0 Participants
Memory Tests Visit 1 - Questions on personal identification answered correctly · Yes	96 Participants
Memory Tests Visit 1 - Questions on personal identification answered correctly · No	0 Participants
Memory Tests Visit 1 - Day of the week answered correctly · No answer	0 Participants
Memory Tests Visit 1 - Day of the week answered correctly · Yes	96 Participants
Memory Tests Visit 1 - Day of the week answered correctly · No	0 Participants
Memory Tests Visit 1 - Arrival at site answered correctly · No answer	2 Participants
Memory Tests Visit 1 - Arrival at site answered correctly · Yes	94 Participants
Memory Tests Visit 1 - Arrival at site answered correctly · No	0 Participants
Memory Tests Visit 1 - 'Why here' answered correctly · No answer	0 Participants
Memory Tests Visit 1 - 'Why here' answered correctly · Yes	96 Participants
Memory Tests Visit 1 - 'Why here' answered correctly · No	0 Participants
Memory Tests Visit 2; prior PDT - All pictures memorized correctly · No answer	0 Participants
Memory Tests Visit 2; prior PDT - All pictures memorized correctly · Yes	100 Participants
Memory Tests Visit 2; prior PDT - All pictures memorized correctly · No	0 Participants
Memory Tests Visit 2; prior PDT - Questions on personal identification answered correctly · No answer	0 Participants
Memory Tests Visit 2; prior PDT - Questions on personal identification answered correctly · Yes	100 Participants
Memory Tests Visit 2; prior PDT - Questions on personal identification answered correctly · No	0 Participants
Memory Tests Visit 2; prior PDT - Day of the week answered correctly · No answer	0 Participants
Memory Tests Visit 2; prior PDT - Day of the week answered correctly · Yes	99 Participants
Memory Tests Visit 2; prior PDT - Day of the week answered correctly · No	1 Participants
Memory Tests Visit 2; prior PDT - Arrival at site answered correctly · No answer	1 Participants
Memory Tests Visit 2; prior PDT - Arrival at site answered correctly · Yes	99 Participants
Memory Tests Visit 2; prior PDT - Arrival at site answered correctly · No	0 Participants
Memory Tests Visit 2; prior PDT - 'Why here' answered correctly · No answer	5 Participants
Memory Tests Visit 2; prior PDT - 'Why here' answered correctly · Yes	95 Participants
Memory Tests Visit 2; prior PDT - 'Why here' answered correctly · No	0 Participants
Memory Tests Visit 2; after end of illumination - All pictures memorized correctly · No answer	0 Participants
Memory Tests Visit 2; after end of illumination - All pictures memorized correctly · Yes	99 Participants
Memory Tests Visit 2; after end of illumination - All pictures memorized correctly · No	1 Participants
Memory Tests Visit 2; after end of illumination - Questions on personal identification answered correctly · No answer	0 Participants
Memory Tests Visit 2; after end of illumination - Questions on personal identification answered correctly · Yes	100 Participants
Memory Tests Visit 2; after end of illumination - Questions on personal identification answered correctly · No	0 Participants
Memory Tests Visit 2; after end of illumination - Day of the week answered correctly · No answer	0 Participants
Memory Tests Visit 2; after end of illumination - Day of the week answered correctly · Yes	100 Participants
Memory Tests Visit 2; after end of illumination - Day of the week answered correctly · No	0 Participants
Memory Tests Visit 2; after end of illumination - Arrival at site answered correctly · No answer	1 Participants
Memory Tests Visit 2; after end of illumination - Arrival at site answered correctly · Yes	99 Participants
Memory Tests Visit 2; after end of illumination - Arrival at site answered correctly · No	0 Participants
Memory Tests Visit 2; after end of illumination - Remembered PDT · No answer	14 Participants
Memory Tests Visit 2; after end of illumination - Remembered PDT · Yes	85 Participants
Memory Tests Visit 2; after end of illumination - Remembered PDT · No	1 Participants
Memory Tests Visit 2; after end of illumination - 'Why here' answered correctly · No answer	4 Participants
Memory Tests Visit 2; after end of illumination - 'Why here' answered correctly · Yes	96 Participants
Memory Tests Visit 2; after end of illumination - 'Why here' answered correctly · No	0 Participants

PRIMARY outcome

Timeframe: At screening (Visit 1, up to 14 days before treatment) and at Visit 2 (treatment day 1)

Population: One subject had no sensitivity assessment at Visit 1, and one other subject had no sensitivity assessment at Visit 2 after end of illumination.

Including investigation of pupils (equality), coordination (finger-nose test), gait (balance), and sensitivity (cheeks, arms, legs); abnormal findings that are considered clinically significant (CS) will be documented

Outcome measures

Measure	Total (BF-200 ALA) n=100 Participants Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Neurological Investigations Visit 1 - Pupils	0 participants with findings considered CS
Neurological Investigations Visit 1 - Coordination	0 participants with findings considered CS
Neurological Investigations Visit 1 - Gait	0 participants with findings considered CS
Neurological Investigations Visit 1 - Sensitivity	0 participants with findings considered CS
Neurological Investigations Visit 2 prior PDT - Pupils	0 participants with findings considered CS
Neurological Investigations Visit 2 prior PDT - Coordination	0 participants with findings considered CS
Neurological Investigations Visit 2 prior PDT - Gait	0 participants with findings considered CS
Neurological Investigations Visit 2 prior PDT - Sensitivity	0 participants with findings considered CS
Neurological Investigations Visit 2 after end of illumination - Pupils	0 participants with findings considered CS
Neurological Investigations Visit 2 after end of illumination - Coordination	0 participants with findings considered CS
Neurological Investigations Visit 2 after end of illumination - Gait	0 participants with findings considered CS
Neurological Investigations Visit 2 after end of illumination - Sensitivity	0 participants with findings considered CS

Adverse Events

Total (BF-200 ALA)

Serious events: 0 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Total (BF-200 ALA) n=100 participants at risk Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single photodynamic therapy (PDT). BF-200 ALA and red light LED lamp: Photodynamic therapy (PDT) using BF-RhodoLED® XL (ALA-PDT, Ameluz®-PDT): Topical application of 3 tubes BF-200 ALA on the expanded treatment field (60 cm²) on the face and/or scalp, followed by red light illumination with BF-RhodoLED® XL after 3 h incubation of study medication under light-tight, occlusive dressing.
Eye disorders Dry eye	3.0% 3/100 • Number of events 3 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Gastrointestinal disorders Nausea	3.0% 3/100 • Number of events 3 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site discharge	4.0% 4/100 • Number of events 4 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site discolouration	6.0% 6/100 • Number of events 6 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site discomfort	11.0% 11/100 • Number of events 13 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site dryness	4.0% 4/100 • Number of events 4 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site erosion	16.0% 16/100 • Number of events 18 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site erythema	86.0% 86/100 • Number of events 97 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site exfoliation	87.0% 87/100 • Number of events 117 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site haemorrhage	10.0% 10/100 • Number of events 10 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site hyperaesthesia	10.0% 10/100 • Number of events 10 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site induration	18.0% 18/100 • Number of events 18 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site oedema	35.0% 35/100 • Number of events 40 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site pain	96.0% 96/100 • Number of events 193 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site papules	2.0% 2/100 • Number of events 2 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site paraesthesia	15.0% 15/100 • Number of events 17 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site pruritus	65.0% 65/100 • Number of events 79 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site scab	49.0% 49/100 • Number of events 58 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site swelling	6.0% 6/100 • Number of events 8 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site vesicles	14.0% 14/100 • Number of events 16 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Application site warmth	17.0% 17/100 • Number of events 20 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Chills	5.0% 5/100 • Number of events 6 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Fatigue	6.0% 6/100 • Number of events 6 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
General disorders Hypothermia	4.0% 4/100 • Number of events 4 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Infections and infestations Application site pustules	3.0% 3/100 • Number of events 3 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Infections and infestations Nasopharyngitis	4.0% 4/100 • Number of events 4 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Infections and infestations Upper respiratory tract infection	2.0% 2/100 • Number of events 2 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Investigations Blood pressure increased	2.0% 2/100 • Number of events 2 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Investigations Gamma-glutamyltransferase increased	2.0% 2/100 • Number of events 2 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	2.0% 2/100 • Number of events 2 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Nervous system disorders Headache	22.0% 22/100 • Number of events 24 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Psychiatric disorders Poor quality sleep	2.0% 2/100 • Number of events 2 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Skin and subcutaneous tissue disorders Actinic keratosis	17.0% 17/100 • Number of events 31 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.
Vascular disorders Hypertension	7.0% 7/100 • Number of events 7 • Collection of adverse events (AEs) starts with signing the informed consent (ICF (≤ 14 days prior to investigational medicinal product (IMP) application) documents until the final Visit (Visit 5, approx. 4 weeks after IMP application). For each subject the duration of the study was approx. 6 weeks (screening up to Visit 5). AEs will be discriminated as pre-treatment adverse events (PTAEs) and treatment emergent adverse events (TEAEs). AEs developing between signing the ICF (Visit 1) and investigational medicinal product (IMP) application at Visit 2 will be considered as PTAEs and documented as an AE. TEAEs are defined as all AEs or SAEs with onset or worsening after treatment with IMP at Visit 2 up to Visit 5.

Additional Information

Clinical Trial Department

Biofrontera Bioscience GmbH

Phone: +49 214 876 32

Email: ameluz@biofrontera.com

Results disclosure agreements

• Principal investigator is a sponsor employee Details of the Study and results shall not be published in any form without prior consent of Sponsor. All decisions on the timing and content of publications/ presentations will be coordinated by Sponsor. A draft of any manuscript, talks, abstracts, and all similar material shall be submitted to sponsor at least sixty (60) days before submission of the final form to any journal, scientific conference, symposium, or program review committee prior to publication or other release.
• Publication restrictions are in place

Restriction type: OTHER