CRC-ACNE-AC-04

Charité-Universitätsmedizin Berlin

Charitéplatz 1, Berlin, Germany, 10117

Dr. Kathrin Hillmann, Charité-Universitätsmedizin Berlin Dept. of Dermatology Clinical Research Center for HairSkin Scie, 0049 30450518499, kathrin.hillmann@charite.de

Dr. Kathrin Hillmann, Charité-Universitätsmedizin Berlin Dept. of Dermatology Clinical Research Center for HairSkin Scie, 0049 30450518499, kathrin.hillmann@charite.de

No

No

No

Final

07 Jul 2014

No

Yes

13 Mar 2014

No

The objective of this trial is to evaluate the efficacy and the tolerability of topically applied 0.1% tyrothricin (Tyrosur® Gel) in patients with mild to severe facial papulopustular acne in comparison to a combination of clindamycin and benzoyl peroxide or to benzoyl peroxide alone.

The medical history of the patient was documented with special emphasis on other skin diseases, like e.g. eczema or contact dermatitis. Furthermore the patient were subjected to a clinical examination in order to measure e.g. the blood pressure and pulse rate and to examine for skin status. Additionally adverse events, serious adverse events and local intolerances were recorded throughout the whole treatment period.

15 Oct 2013

No

No

Germany: 24

24

24

0

0

0

0

0

0

24

0

0

Inclusion

Randomised - controlled

In this clinical trial, a single blind concept was chosen. The investigators were blinded to the study medication and had neither access to the randomization list nor to the drug accountability log and were not present during product application. Product application was conducted solely by the study nurses. Due to original, unblinded packaging of the products, subjects and responsible study nurses were not blinded to the study medication.

No

Tyrosur Gel

0.1% Tyrothricin

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. Every patient received treatment with 0.1% tyrothricin (Tyrosur® Gel) on one half of the face in a thin layer. The side of the face treated with 0.1% tyrothricin (Tyrosur® Gel) was randomized.No application was performed in the direct area around the eyes and on the lips of the patients.

Duac Acne Gel

Clindamycin and BPO

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not assigned to Tyrosur Gel, a combination of clindamycin and BPO (Duac Acne Gel®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

BPO 5%

Aknefug Oxid mild 5%

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not allocated to Tyrosur Gel, BPO 5% alone (Aknefug Oxid mild 5%®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

Visit 2

Randomised - controlled

In this clinical trial, a single blind concept was chosen. The investigators were blinded to the study medication and had neither access to the randomization list nor to the drug accountability log and were not present during product application. Product application was conducted solely by the study nurses. Due to original, unblinded packaging of the products, subjects and responsible study nurses were not blinded to the study medication.

No

Tyrosur Gel

0.1% Tyrothricin

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. Every patient received treatment with 0.1% tyrothricin (Tyrosur® Gel) on one half of the face in a thin layer. The side of the face treated with 0.1% tyrothricin (Tyrosur® Gel) was randomized.No application was performed in the direct area around the eyes and on the lips of the patients.

Duac Acne Gel

Clindamycin and BPO

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not assigned to Tyrosur Gel, a combination of clindamycin and BPO (Duac Acne Gel®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

BPO 5%

Aknefug Oxid mild 5%

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not allocated to Tyrosur Gel, BPO 5% alone (Aknefug Oxid mild 5%®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

Visit 3

Randomised - controlled

In this clinical trial, a single blind concept was chosen. The investigators were blinded to the study medication and had neither access to the randomization list nor to the drug accountability log and were not present during product application. Product application was conducted solely by the study nurses. Due to original, unblinded packaging of the products, subjects and responsible study nurses were not blinded to the study medication.

No

Tyrosur Gel

0.1% Tyrothricin

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. Every patient received treatment with 0.1% tyrothricin (Tyrosur® Gel) on one half of the face in a thin layer. The side of the face treated with 0.1% tyrothricin (Tyrosur® Gel) was randomized.No application was performed in the direct area around the eyes and on the lips of the patients.

Duac Acne Gel

Clindamycin and BPO

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not assigned to Tyrosur Gel, a combination of clindamycin and BPO (Duac Acne Gel®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

BPO 5%

Aknefug Oxid mild 5%

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not allocated to Tyrosur Gel, BPO 5% alone (Aknefug Oxid mild 5%®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

Visit 4

Randomised - controlled

In this clinical trial, a single blind concept was chosen. The investigators were blinded to the study medication and had neither access to the randomization list nor to the drug accountability log and were not present during product application. Product application was conducted solely by the study nurses. Due to original, unblinded packaging of the products, subjects and responsible study nurses were not blinded to the study medication.

No

Tyrosur Gel

0.1% Tyrothricin

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. Every patient received treatment with 0.1% tyrothricin (Tyrosur® Gel) on one half of the face in a thin layer. The side of the face treated with 0.1% tyrothricin (Tyrosur® Gel) was randomized.No application was performed in the direct area around the eyes and on the lips of the patients.

Duac Acne Gel

Clindamycin and BPO

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not assigned to Tyrosur Gel, a combination of clindamycin and BPO (Duac Acne Gel®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

BPO 5%

Aknefug Oxid mild 5%

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not allocated to Tyrosur Gel, BPO 5% alone (Aknefug Oxid mild 5%®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

Visit 5

Randomised - controlled

In this clinical trial, a single blind concept was chosen. The investigators were blinded to the study medication and had neither access to the randomization list nor to the drug accountability log and were not present during product application. Product application was conducted solely by the study nurses. Due to original, unblinded packaging of the products, subjects and responsible study nurses were not blinded to the study medication.

No

Tyrosur Gel

0.1% Tyrothricin

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. Every patient received treatment with 0.1% tyrothricin (Tyrosur® Gel) on one half of the face in a thin layer. The side of the face treated with 0.1% tyrothricin (Tyrosur® Gel) was randomized.No application was performed in the direct area around the eyes and on the lips of the patients.

Duac Acne Gel

Clindamycin and BPO

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not assigned to Tyrosur Gel, a combination of clindamycin and BPO (Duac Acne Gel®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

BPO 5%

Aknefug Oxid mild 5%

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not allocated to Tyrosur Gel, BPO 5% alone (Aknefug Oxid mild 5%®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

Visit 6

Randomised - controlled

In this clinical trial, a single blind concept was chosen. The investigators were blinded to the study medication and had neither access to the randomization list nor to the drug accountability log and were not present during product application. Product application was conducted solely by the study nurses. Due to original, unblinded packaging of the products, subjects and responsible study nurses were not blinded to the study medication.

No

Tyrosur Gel

0.1% Tyrothricin

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. Every patient received treatment with 0.1% tyrothricin (Tyrosur® Gel) on one half of the face in a thin layer. The side of the face treated with 0.1% tyrothricin (Tyrosur® Gel) was randomized.No application was performed in the direct area around the eyes and on the lips of the patients.

Duac Acne Gel

Clindamycin and BPO

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not assigned to Tyrosur Gel, a combination of clindamycin and BPO (Duac Acne Gel®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

BPO 5%

Aknefug Oxid mild 5%

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not allocated to Tyrosur Gel, BPO 5% alone (Aknefug Oxid mild 5%®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

Visit 7

Randomised - controlled

In this clinical trial, a single blind concept was chosen. The investigators were blinded to the study medication and had neither access to the randomization list nor to the drug accountability log and were not present during product application. Product application was conducted solely by the study nurses. Due to original, unblinded packaging of the products, subjects and responsible study nurses were not blinded to the study medication.

No

Tyrosur Gel

0.1% Tyrothricin

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. Every patient received treatment with 0.1% tyrothricin (Tyrosur® Gel) on one half of the face in a thin layer. The side of the face treated with 0.1% tyrothricin (Tyrosur® Gel) was randomized.No application was performed in the direct area around the eyes and on the lips of the patients.

Duac Acne Gel

Clindamycin and BPO

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not assigned to Tyrosur Gel, a combination of clindamycin and BPO (Duac Acne Gel®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

BPO 5%

Aknefug Oxid mild 5%

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not allocated to Tyrosur Gel, BPO 5% alone (Aknefug Oxid mild 5%®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

Visit 8

Randomised - controlled

In this clinical trial, a single blind concept was chosen. The investigators were blinded to the study medication and had neither access to the randomization list nor to the drug accountability log and were not present during product application. Product application was conducted solely by the study nurses. Due to original, unblinded packaging of the products, subjects and responsible study nurses were not blinded to the study medication.

No

Tyrosur Gel

0.1% Tyrothricin

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. Every patient received treatment with 0.1% tyrothricin (Tyrosur® Gel) on one half of the face in a thin layer. The side of the face treated with 0.1% tyrothricin (Tyrosur® Gel) was randomized.No application was performed in the direct area around the eyes and on the lips of the patients.

Duac Acne Gel

Clindamycin and BPO

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not assigned to Tyrosur Gel, a combination of clindamycin and BPO (Duac Acne Gel®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

BPO 5%

Aknefug Oxid mild 5%

Gel

Topical

On 24 consecutive days, the study products were applied topically according to the randomization list once daily in the evening at the study center on the related areas of patient´s face over a trial period of 25 days by the study nurse. On the other half of the patient's face, not allocated to Tyrosur Gel, BPO 5% alone (Aknefug Oxid mild 5%®) was applied in a thin layer on the related areas according to randomization. No application was performed in the direct area around the eyes and on the lips of the patients.

0.1 % Tyrothricin

Clindamycin + BPO

BPO 5%

0.1 % Tyrothricin

Clindamycin + BPO

BPO 5%

0.1% Tyrothricin

Clindamcin + BPO

BPO 5%

0.1% Tyrothricin

Clindamycin + BPO

BPO 5%

0.1% Tyrothricin

Clindamycin + BPO

BPO 5%

0.1% Tyrothricin

Clindamycin + BPO

BPO 5%

0.1% Tyrothricin

Clindamycin + BPO

BPO 5%

0.1% Tyrothricin

Clindamycin + BPO

BPO 5%

0.1% Tyrothricin

Clindamycin + BPO

BPO 5%

At the screening / inclusion visit the inflammatory lesions (papules and pustules, nodules and cysts) in the patient´s face (forehead, cheeks and region of the chin) excluding the nasal region were counted by the investigator. Each side of the face was assessed separately. The counting was repeated on Day 4 and 8 ± 1d (visit 2, 3), Day 12 and 15 ± 1d (visit 4, 5), Day 18 and 22 ± 1d (visit 6, 7), and Day 25 ± 1d (visit 8). The absolute change or the reduction of inflammatory lesion count between the inclusion visit and each subsequent visit was determined. Finally, the change in inflammatory lesion counts over all measurement time points was considered.

Primary

Over 25 consecutive days. The count of lesion numbers occured only on Day 4 and 8 ± 1d (visit 2, 3), Day 12 and 15 ± 1d (visit 4, 5), Day 18 and 22 ± 1d (visit 6, 7), and Day 25 ± 1d (visit 8).

0.1 % Tyrothricin v Clindamycin + BPO v BPO 5% v 0.1% Tyrothricin v 0.1% Tyrothricin v Clindamycin + BPO v Clindamycin + BPO v BPO 5% v BPO 5%

140

Pre-specified

At screening / inclusion visit the non-inflammatory lesions (open and closed comedones) in the patient´s face (forehead, cheeks and region of the chin) excluding the nasal region were counted by the investigator. Each side of the face was assessed separately. The counting was repeated on Day 4 and 8 ± 1d (visit 2, 3), Day 12 and 15 ± 1d (visit 4, 5), Day 18 and 22 ± 1d (visit 6, 7), and Day 25 ± 1d (visit 8). Then the absolute change or the reduction of noninflammatory lesion count between the inclusion visit and each subsequent visit was determined respectively. Finally, the change in non-inflammatory lesion counts over all measurement time points was considered.

Primary

The counting was conducted at the inclusion visit, and repeated on Day 4 and 8 ± 1d (visit 2, 3), Day 12 and 15 ± 1d (visit 4, 5), Day 18 and 22 ± 1d (visit 6, 7), and Day 25 ± 1d (visit 8).

0.1 % Tyrothricin v Clindamycin + BPO v BPO 5% v 0.1% Tyrothricin v 0.1% Tyrothricin v Clindamycin + BPO v Clindamycin + BPO v BPO 5% v BPO 5%

129

Pre-specified

Treatment success was determined by the improvement in ISGA. At inclusion visit and at each following visit (2 - 8) the investigator assessed the acne severity by using the ISGA 6- point scale. Only patients with an Investigator´s Static Global Assessment Score (ISGA) of 2 to 4 will were enrolled in the trial. Each side of the face was assessed separately. Finally, the absolute and relative ISGA score change between inclusion and each subsequent visit was determined. According to the recommendation of the U.S. Food and Drug Administration (FDA) the ISGA score was also dichotomized. Treatment success was defined as improvement by at least two grades from the baseline score. Subjects were discontinued from the trial by the investigator at any time if the ISGA increased for one or more grades from baseline.

Secondary

At inclusion visit and at each following visit (2 - 8) the investigator assessed the acne severity by using the ISGA 6-point scale.

At the inclusion visit and at each of the following visits the sebum level was determined with a photometric device (Sebumeter®, Courage+Khazaka electronic GmbH). The early, mild non-inflammatory lesions (microcomedones and comedones) are associated with higher sebum amount and higher fluorescence intensity, while the late, severe inflammatory lesions (pustules, papules, nodules and cysts) are associated with lower sebum amount and lower fluorescence intensity. This suggests that the increased sebum secretion and the presence of Propionibacteria are predominantly involved in the initial stages of acne development. A special opaque plastic tape (64 mm2) was pressed onto the designated skin areas (separately for left and right)25 for 30 seconds with a slight pressure to collect the sebum. The resulting increase in transparency of the tape was be measured. The displayed values corresponded to the sebum amount on the skin surface in micrograms of sebum per square centimeters.

Secondary

Sebum content was measured at the inclusion visit and every subsequent visit (Visit 2-8).

At the inclusion visit and at each of the following visits follicular fluorescence was determined by Visiopor® PP34N camera. The camera head was placed on the relevant skin areas.23 Measurements were made separately on the right and left side of the face on four designated areas. The parameters analyzed were the number and the percentage of the area covered by orange-red spots. The orange-red fluorescence shows stronger correlation with the presence of non-inflammatory acne lesions (comedones) and high sebum amount than the presence of inflammatory acne lesions (pustules) and low sebum amount. Yellow color spots in the images were excluded from the analysis. The absolute change in follicular fluorescence was evaluated. The measurement was repeated twice.

Secondary

Visiopor was measured at the inclusion visit as well as all subsequent visits (Visit 2-8).

At the inclusion visit and at each of the following visits follicular fluorescence was determined by Visiopor® PP34N camera. The camera head was placed on the relevant skin areas.23 Measurements were made separately on the right and left side of the face on four designated areas. The parameters analyzed were the number and the percentage of the area covered by orange-red spots. Yellow color spots in the images were excluded from the analysis. The absolute change in follicular fluorescence was evaluated. The measurement was repeated twice.

Secondary

Fluorensce size (Visipor) was measured at inclusion visit, as well as all subseuqent visits (Visit 2-8).

AEs and SAEs were followed throughout the duration of the study. At each subject visit the investigator enquired about any local intolerance or AE using open questions, taking care not to influence the subjects answer.

At each visit the investigator enquired about any AE by interviewing the subject using an open question, taking care not to influence the subject’s answer, and if appropriate a clinical examination. Information regarding AE was immediately recorded in the CRF, and if a concomitant medication was reported an AE and reason for use was documented.

17.1

Edema to tyrothricin