Trial Outcomes & Findings for Study to Find Out if Cream V61-044 Used to Treat Fungal Infections Causes an Allergic Skin Reaction to Sunlight in Healthy Participants (NCT NCT04532164)

Results Overview

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Challenge Phase, each subject had the following four virgin test sites: Treated irradiated test site; Treated non-irradiated test site; Untreated irradiated test site; Untreated non-irradiated test site. All four test sites were evaluated according to the above scoring system at 24, 48, and 72 hours following patch application (3 different time points), and the number of test sites with available scores from all these time points were reported for all treated subjects.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

137 participants

Primary outcome timeframe

At 24, 48, and 72 hours following patch application

Results posted on

2020-11-16

Participant Flow

Study was conducted at single center in the US, between 10 JUN 2013 (first subject first visit) and 11 NOV 2013 (last subject last visit).

A total of 137 subjects were enrolled in the study and 132 received study treatment.

Participant milestones

Participant milestones
Measure	Photoallergic Reaction Test During the Induction Phase, participants received Butenafine HCl 1% on the treated irradiated skin test site followed by UV irradiation and on the treated non-irradiated skin test site without UV radiation, two times per week for three consecutive weeks. After 10 days of Rest Phase, during the Challenge Phase, participants received same procedure on the two virgin sites (treated sites) as in Induction Phase, and two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Test sites were evaluated at 24, 48, and 72 hours after irradiation using the same grading scale used during Induction Phase.
Overall Study STARTED	137
Overall Study Treated	132
Overall Study COMPLETED	113
Overall Study NOT COMPLETED	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Photoallergic Reaction Test During the Induction Phase, participants received Butenafine HCl 1% on the treated irradiated skin test site followed by UV irradiation and on the treated non-irradiated skin test site without UV radiation, two times per week for three consecutive weeks. After 10 days of Rest Phase, during the Challenge Phase, participants received same procedure on the two virgin sites (treated sites) as in Induction Phase, and two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Test sites were evaluated at 24, 48, and 72 hours after irradiation using the same grading scale used during Induction Phase.
Overall Study Adverse Event	1
Overall Study Protocol Violation	5
Overall Study Lost to Follow-up	1
Overall Study Found to be Ineligible	3
Overall Study Withdrawal by Subject	14

Baseline Characteristics

Study to Find Out if Cream V61-044 Used to Treat Fungal Infections Causes an Allergic Skin Reaction to Sunlight in Healthy Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Photoallergic Reaction Test n=137 Participants During the Induction Phase, participants received Butenafine HCl 1% on the treated irradiated skin test site followed by UV irradiation and on the treated non-irradiated skin test site without UV radiation, two times per week for three consecutive weeks. After 10 days of Rest Phase, during the Challenge Phase, participants received same procedure on the two virgin sites (treated sites) as in Induction Phase, and two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Test sites were evaluated at 24, 48, and 72 hours after irradiation using the same grading scale used during Induction Phase.
Age, Continuous	41.8 Years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	89 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	99 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	34 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/Hispanic	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/Asian	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 24, 48, and 72 hours following patch application

Population: Subjects who received treatment

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Challenge Phase, each subject had the following four virgin test sites: Treated irradiated test site; Treated non-irradiated test site; Untreated irradiated test site; Untreated non-irradiated test site. All four test sites were evaluated according to the above scoring system at 24, 48, and 72 hours following patch application (3 different time points), and the number of test sites with available scores from all these time points were reported for all treated subjects.

Outcome measures

Outcome measures
Measure	Butenafine HCl 1% (BAY1896425) - Challenge Phase n=349 Test site 5 μl/cm\^2 of the Butenafine HCl 1% was applied directly to each of the two virgin sites (treated sites) adjacent to the induction patch sites and covered with Hilltop chambers with Webril pad and tape was applied over the chambers to secure the occlusive patches to the skin. Two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Sites were at least 2.5 cm apart. The patches were removed 24 hours later and the sites were lightly wiped. Test sites were evaluated. Butenafine HCl 1% (2 μl/cm\^2) was applied to the treated irradiated site. After 15 minutes, the treated irradiated site and the untreated irradiated site were irradiated with 0.5 MED of UVA/UVB irradiation followed by 10 Joules/cm\^2 of UVA from a xenon arc solar simulator equipped with a Schott WG345 to eliminate UVB radiation. The remaining sites served as the treated non-irradiated site and untreated non-irradiated site.
Photoallergic Reaction Evaluation Reported as Number of Test Site With Different Erythema Score During Challenge Phase - All Treated Subjects Treated irradiated test site, score=0	325 Test site
Photoallergic Reaction Evaluation Reported as Number of Test Site With Different Erythema Score During Challenge Phase - All Treated Subjects Treated irradiated test site, score=1	24 Test site
Photoallergic Reaction Evaluation Reported as Number of Test Site With Different Erythema Score During Challenge Phase - All Treated Subjects Treated non-irradiated test site, score=0	343 Test site
Photoallergic Reaction Evaluation Reported as Number of Test Site With Different Erythema Score During Challenge Phase - All Treated Subjects Treated non-irradiated test site, score=1	6 Test site

PRIMARY outcome

Timeframe: At 24, 48, and 72 hours following patch application

Population: Subjects who received treatment and completed the trial and had evaluable data

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Challenge Phase, each subject had the following four virgin test sites: Treated irradiated test site; Treated non-irradiated test site; Untreated irradiated test site; Untreated non-irradiated test site. All four test sites were evaluated according to the above scoring system at 24, 48, and 72 hours following patch application (3 different time points), and the number of test sites with available scores from all these time points were reported for all evaluable subjects.

Outcome measures

Outcome measures
Measure	Butenafine HCl 1% (BAY1896425) - Challenge Phase n=320 Test site 5 μl/cm\^2 of the Butenafine HCl 1% was applied directly to each of the two virgin sites (treated sites) adjacent to the induction patch sites and covered with Hilltop chambers with Webril pad and tape was applied over the chambers to secure the occlusive patches to the skin. Two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Sites were at least 2.5 cm apart. The patches were removed 24 hours later and the sites were lightly wiped. Test sites were evaluated. Butenafine HCl 1% (2 μl/cm\^2) was applied to the treated irradiated site. After 15 minutes, the treated irradiated site and the untreated irradiated site were irradiated with 0.5 MED of UVA/UVB irradiation followed by 10 Joules/cm\^2 of UVA from a xenon arc solar simulator equipped with a Schott WG345 to eliminate UVB radiation. The remaining sites served as the treated non-irradiated site and untreated non-irradiated site.
Photoallergic Reaction Evaluation Reported as Number of Test Site With Different Erythema Score During Challenge Phase - All Evaluable Subjects Treated irradiated test site, score=0	311 Test site
Photoallergic Reaction Evaluation Reported as Number of Test Site With Different Erythema Score During Challenge Phase - All Evaluable Subjects Treated irradiated test site, score=1	9 Test site
Photoallergic Reaction Evaluation Reported as Number of Test Site With Different Erythema Score During Challenge Phase - All Evaluable Subjects Treated non-irradiated test site, score=0	314 Test site
Photoallergic Reaction Evaluation Reported as Number of Test Site With Different Erythema Score During Challenge Phase - All Evaluable Subjects Treated non-irradiated test site, score=1	6 Test site

SECONDARY outcome

Timeframe: Two or three days after each irradiation during Induction Phase

Population: Subjects who received treatment

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Induction Phase, each subject had the following two test sites: Treated irradiated test site and Treated non-irradiated test site. The number of test sites with available scores from all 6 induction patches were reported for all treated subjects.

Outcome measures

Outcome measures
Measure	Butenafine HCl 1% (BAY1896425) - Challenge Phase n=630 Test site 5 μl/cm\^2 of the Butenafine HCl 1% was applied directly to each of the two virgin sites (treated sites) adjacent to the induction patch sites and covered with Hilltop chambers with Webril pad and tape was applied over the chambers to secure the occlusive patches to the skin. Two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Sites were at least 2.5 cm apart. The patches were removed 24 hours later and the sites were lightly wiped. Test sites were evaluated. Butenafine HCl 1% (2 μl/cm\^2) was applied to the treated irradiated site. After 15 minutes, the treated irradiated site and the untreated irradiated site were irradiated with 0.5 MED of UVA/UVB irradiation followed by 10 Joules/cm\^2 of UVA from a xenon arc solar simulator equipped with a Schott WG345 to eliminate UVB radiation. The remaining sites served as the treated non-irradiated site and untreated non-irradiated site.
Development of Erythema on Treated Irradiated Test Sites During Induction Phase - All Treated Subjects Treated irradiated test site, score=0	273 Test site
Development of Erythema on Treated Irradiated Test Sites During Induction Phase - All Treated Subjects Treated irradiated test site, score=1	282 Test site
Development of Erythema on Treated Irradiated Test Sites During Induction Phase - All Treated Subjects Treated irradiated test site, score=2	75 Test site

SECONDARY outcome

Timeframe: Two or three days after each irradiation during Induction Phase

Population: Subjects who received treatment

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Induction Phase, each subject had the following two test sites: Treated irradiated test site and Treated non-irradiated test site. The mean score of test sites with available scores from all 6 induction patches were reported for all treated subjects.

Outcome measures

Outcome measures
Measure	Butenafine HCl 1% (BAY1896425) - Challenge Phase n=630 Test site 5 μl/cm\^2 of the Butenafine HCl 1% was applied directly to each of the two virgin sites (treated sites) adjacent to the induction patch sites and covered with Hilltop chambers with Webril pad and tape was applied over the chambers to secure the occlusive patches to the skin. Two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Sites were at least 2.5 cm apart. The patches were removed 24 hours later and the sites were lightly wiped. Test sites were evaluated. Butenafine HCl 1% (2 μl/cm\^2) was applied to the treated irradiated site. After 15 minutes, the treated irradiated site and the untreated irradiated site were irradiated with 0.5 MED of UVA/UVB irradiation followed by 10 Joules/cm\^2 of UVA from a xenon arc solar simulator equipped with a Schott WG345 to eliminate UVB radiation. The remaining sites served as the treated non-irradiated site and untreated non-irradiated site.
Development of Erythema on the Treated Non-irradiated Test Sites During Induction Phase - All Treated Subjects	0 Score on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: At 24, 48, and 72 hours following patch application

Population: Subjects who received treatment

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Challenge Phase, each subject had the following four virgin test sites: Treated irradiated test site; Treated non-irradiated test site; Untreated irradiated test site; Untreated non-irradiated test site. All four test sites were evaluated according to the above scoring system at 24, 48, and 72 hours following patch application (3 different time points), and the number of test sites with available scores from all these time points were reported for all treated subjects.

Outcome measures

Outcome measures
Measure	Butenafine HCl 1% (BAY1896425) - Challenge Phase n=349 Test site 5 μl/cm\^2 of the Butenafine HCl 1% was applied directly to each of the two virgin sites (treated sites) adjacent to the induction patch sites and covered with Hilltop chambers with Webril pad and tape was applied over the chambers to secure the occlusive patches to the skin. Two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Sites were at least 2.5 cm apart. The patches were removed 24 hours later and the sites were lightly wiped. Test sites were evaluated. Butenafine HCl 1% (2 μl/cm\^2) was applied to the treated irradiated site. After 15 minutes, the treated irradiated site and the untreated irradiated site were irradiated with 0.5 MED of UVA/UVB irradiation followed by 10 Joules/cm\^2 of UVA from a xenon arc solar simulator equipped with a Schott WG345 to eliminate UVB radiation. The remaining sites served as the treated non-irradiated site and untreated non-irradiated site.
Development of Erythema on the Treated Non-irradiated Test Sites During Challenge Phase Reported as Number of Test Site With Different Erythema Score - All Treated Subjects Treated non-irradiated test site, score=0	343 Test site
Development of Erythema on the Treated Non-irradiated Test Sites During Challenge Phase Reported as Number of Test Site With Different Erythema Score - All Treated Subjects Treated non-irradiated test site, score=1	6 Test site

SECONDARY outcome

Timeframe: Two or three days after each irradiation during Induction Phase

Population: Subjects who received treatment and completed the trial and had evaluable data

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Induction Phase, each subject had the following two test sites: Treated irradiated test site and Treated non-irradiated test site. The number of test sites with available scores from all 6 induction patches were reported for all evaluable subjects.

Outcome measures

Outcome measures
Measure	Butenafine HCl 1% (BAY1896425) - Challenge Phase n=540 Test site 5 μl/cm\^2 of the Butenafine HCl 1% was applied directly to each of the two virgin sites (treated sites) adjacent to the induction patch sites and covered with Hilltop chambers with Webril pad and tape was applied over the chambers to secure the occlusive patches to the skin. Two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Sites were at least 2.5 cm apart. The patches were removed 24 hours later and the sites were lightly wiped. Test sites were evaluated. Butenafine HCl 1% (2 μl/cm\^2) was applied to the treated irradiated site. After 15 minutes, the treated irradiated site and the untreated irradiated site were irradiated with 0.5 MED of UVA/UVB irradiation followed by 10 Joules/cm\^2 of UVA from a xenon arc solar simulator equipped with a Schott WG345 to eliminate UVB radiation. The remaining sites served as the treated non-irradiated site and untreated non-irradiated site.
Development of Erythema on Treated Irradiated Test Sites During Induction Phase - All Evaluable Subjects Treated irradiated test site, score=0	248 Test site
Development of Erythema on Treated Irradiated Test Sites During Induction Phase - All Evaluable Subjects Treated irradiated test site, score=1	231 Test site
Development of Erythema on Treated Irradiated Test Sites During Induction Phase - All Evaluable Subjects Treated irradiated test site, score=2	61 Test site

SECONDARY outcome

Timeframe: Two or three days after each irradiation during Induction Phase

Population: Subjects who received treatment and completed the trial and had evaluable data

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Induction Phase, each subject had the following two test sites: Treated irradiated test site and Treated non-irradiated test site. The mean score of test sites with available scores from all 6 induction patches were reported for all evaluable subjects.

Outcome measures

Outcome measures
Measure	Butenafine HCl 1% (BAY1896425) - Challenge Phase n=540 Test site 5 μl/cm\^2 of the Butenafine HCl 1% was applied directly to each of the two virgin sites (treated sites) adjacent to the induction patch sites and covered with Hilltop chambers with Webril pad and tape was applied over the chambers to secure the occlusive patches to the skin. Two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Sites were at least 2.5 cm apart. The patches were removed 24 hours later and the sites were lightly wiped. Test sites were evaluated. Butenafine HCl 1% (2 μl/cm\^2) was applied to the treated irradiated site. After 15 minutes, the treated irradiated site and the untreated irradiated site were irradiated with 0.5 MED of UVA/UVB irradiation followed by 10 Joules/cm\^2 of UVA from a xenon arc solar simulator equipped with a Schott WG345 to eliminate UVB radiation. The remaining sites served as the treated non-irradiated site and untreated non-irradiated site.
Development of Erythema on the Treated Non-irradiated Test Sites During Induction Phase - All Evaluable Subjects	0 Score on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: At 24, 48, and 72 hours following patch application

Population: Subjects who received treatment and completed the trial and had evaluable data

Evaluation of the test sites after irradiation used following scoring system: score 0=normal skin (no visible reaction); score 1= faint, barely perceptible to moderate redness with poorly defined margins (not clinically significant); score 2=moderate to intense redness with well defined margins; score 3=redness with well defined edema; score 4=redness with papules, vesicles, or ulceration. During Challenge Phase, each subject had the following four virgin test sites: Treated irradiated test site; Treated non-irradiated test site; Untreated irradiated test site; Untreated non-irradiated test site. All four test sites were evaluated according to the above scoring system at 24, 48, and 72 hours following patch application (3 different time points), and the number of test sites with available scores from all these time points were reported for all evaluable subjects.

Outcome measures

Outcome measures
Measure	Butenafine HCl 1% (BAY1896425) - Challenge Phase n=320 Test site 5 μl/cm\^2 of the Butenafine HCl 1% was applied directly to each of the two virgin sites (treated sites) adjacent to the induction patch sites and covered with Hilltop chambers with Webril pad and tape was applied over the chambers to secure the occlusive patches to the skin. Two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Sites were at least 2.5 cm apart. The patches were removed 24 hours later and the sites were lightly wiped. Test sites were evaluated. Butenafine HCl 1% (2 μl/cm\^2) was applied to the treated irradiated site. After 15 minutes, the treated irradiated site and the untreated irradiated site were irradiated with 0.5 MED of UVA/UVB irradiation followed by 10 Joules/cm\^2 of UVA from a xenon arc solar simulator equipped with a Schott WG345 to eliminate UVB radiation. The remaining sites served as the treated non-irradiated site and untreated non-irradiated site.
Development of Erythema on the Treated Non-irradiated Test Sites During Challenge Phase Reported as Number of Test Site With Different Erythema Score - All Evaluable Subjects Treated non-irradiated test site, score=0	314 Test site
Development of Erythema on the Treated Non-irradiated Test Sites During Challenge Phase Reported as Number of Test Site With Different Erythema Score - All Evaluable Subjects Treated non-irradiated test site, score=1	6 Test site

Adverse Events

Photoallergic Reaction Test

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Photoallergic Reaction Test n=137 participants at risk During the Induction Phase, participants received Butenafine HCl 1% on the treated irradiated skin test site followed by UV irradiation and on the treated non-irradiated skin test site without UV radiation, two times per week for three consecutive weeks. After 10 days of Rest Phase, during the Challenge Phase, participants received same procedure on the two virgin sites (treated sites) as in Induction Phase, and two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Test sites were evaluated at 24, 48, and 72 hours after irradiation using the same grading scale used during Induction Phase.
Metabolism and nutrition disorders Dehydration	0.73% 1/137 • Number of events 1 • 5 weeks
Gastrointestinal disorders Diarrhea	0.73% 1/137 • Number of events 1 • 5 weeks
Gastrointestinal disorders Vomiting	0.73% 1/137 • Number of events 1 • 5 weeks

Other adverse events

Other adverse events
Measure	Photoallergic Reaction Test n=137 participants at risk During the Induction Phase, participants received Butenafine HCl 1% on the treated irradiated skin test site followed by UV irradiation and on the treated non-irradiated skin test site without UV radiation, two times per week for three consecutive weeks. After 10 days of Rest Phase, during the Challenge Phase, participants received same procedure on the two virgin sites (treated sites) as in Induction Phase, and two additional sites with no Butenafine HCl 1% (untreated sites) were also occluded. Test sites were evaluated at 24, 48, and 72 hours after irradiation using the same grading scale used during Induction Phase.
Gastrointestinal disorders Toothache	0.73% 1/137 • Number of events 1 • 5 weeks
Reproductive system and breast disorders Dysmenorrhea	0.73% 1/137 • Number of events 2 • 5 weeks
Musculoskeletal and connective tissue disorders Pain in extremity	0.73% 1/137 • Number of events 1 • 5 weeks
Musculoskeletal and connective tissue disorders Other (Ankle Sprain)	0.73% 1/137 • Number of events 1 • 5 weeks
Nervous system disorders Headache	1.5% 2/137 • Number of events 2 • 5 weeks
Infections and infestations Other (Insect Bite)	0.73% 1/137 • Number of events 1 • 5 weeks
Infections and infestations Eye Infection	0.73% 1/137 • Number of events 1 • 5 weeks
Eye disorders Watery eyes	0.73% 1/137 • Number of events 2 • 5 weeks

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No information based on the conduct of the study (incl. protocol, data resulting from the study, or the fact that the study was being conducted) will be released without prior written consent of the sponsor unless the requirement is superseded by State or Federal law.
Publication restrictions are in place

Restriction type: OTHER