A Randomized, Double-blinded Placebo-controlled Study to Investigate Antimicrobial Efficacy and Safety Following Topical Application of DPK-060

Study Overview
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Brief Summary
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The primary objective of this study was to evaluate microbial density in eczematous lesions during two weeks of twice daily therapy with the investigational product, DPK-060 1% ointment, compared with placebo in patients with atopic dermatitis. This randomized, double-blind, placebo-controlled part of the study was preceded with an open-label investigation in a small group of patients (n=5) treated with two applications of DPK-060 1% ointment per day for four days to assess safety, local tolerability and systemic absorption of DPK-060. The secondary objectives were to evaluate severity of eczema and pruritus, to assess the tolerability and safety of the treatment and to assess the degree of systemic absorption of DPK-060 in blood on Day 7 and Day 21 in a sub-set of 10 patients.

Official Title
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A Randomized, Double-blinded Placebo-controlled Study to Investigate Antimicrobial Efficacy and Safety Following Topical Application of DPK-060

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: DPK-060 1% ointment
* Drug: Placebo for DPK-060 ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical diagnosis of atopic dermatitis Treatable eczematous lesions of a total area of at least 25 cm2 (100 cm2 for the initial five patients) Female patients of childbearing potential had to be using an appropriate method of contraception. Female patients of childbearing potential were not eligible before PK data from the first 10 patients had been evaluated and the Medical Products Agency (Swedish regulatory agency) had given approval to include women of childbearing potential. Exclusion Criteria: Significant clinical illness, within the two weeks prior to first dose, which could affect the outcome of the study Previous local or systemic antimicrobial therapy within the last four weeks prior to the first application of the investigational product (DPK-060 1% or placebo ointment) Existence of any surgical or medical condition which, in the judgment of the investigator, might interfere with the absorption, distribution, metabolism or excretion of the drug Patients who had had systemic treatment for atopic dermatitis or other topical or transdermal treatments (such as nicotine, hormone replacement therapies)on the site of eczema within 14 days prior to first application of DPK-060 1% or placebo ointment and/or topical treatment with tar, any corticosteroid,topical immunomodulators or oral treatment with any corticosteroids within 14 days prior to first application and/or oral antihistamines within 14 days of the first dose. A need for any other medication during the period 0 to 7 days before entry to the study, (excluding the oral contraceptive pill for females) except those deemed by the principal investigator / clinical investigator not to interfere with the outcome of the study Diagnosis of other skin diseases, which in the opinion of the investigator, were likely to adversely affect the outcome of the study History or evidence of significant cardiac, renal, hepatic or endocrine disease Significant hypersensitivity or allergy, as judged by the investigator Immunocompromised patients Lice or scabies Tinea corporis Hypersensitivity to the ingredients of the vehicle The presence of prominent tattoos at sites of application of DPK-060 1% or placebo ointment Donation of blood, exceeding 450 mL, during the three months prior to first dose Participation in a clinical study during the 12 weeks prior to first dose Ongoing alcohol or drug abuse Positive pregnancy test or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo for DPK-060 ointment<br> | Drug: Placebo for DPK-060 ointment<br>* Placebo for DPK-060 ointment applied to the skin, two applications per day using approximately 3 mg ointment per cm2<br>|
| Experimental: DPK-060 1% ointment<br> | Drug: DPK-060 1% ointment<br>* DPK-060 1% ointment applied to the skin, two applications per day using approximately 3 mg ointment per cm2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Microbial Colony Forming Units (CFU) Count at Day 14 Full Analysis Set | The total microbial colony forming units count is the number of CFU/cm2 for total microbial count in eczematous lesions. | Baseline and Day 14 | 
| Percent Change From Baseline in Total Microbial Colony Forming Units (CFU) Count at Day 14 Per Protocol Analysis Set | The total microbial colony forming units count is the number of CFU/cm2 for total microbial count in eczematous lesions. | Baseline and Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Microbial Colony Forming Units (CFU) Count at Day 7 and 21 Full Analysis Set | The total microbial colony forming units count is the number of CFU/cm2 for total microbial count in eczematous lesions. | Baseline, Day 7 and 21 | 
| Percent Change From Baseline in Total Microbial Colony Forming Units (CFU) Count at Day 7 and 21 Per Protocol Analysis Set | The total microbial colony forming units count is the number of CFU/cm2 for total microbial count in eczematous lesions. | Baseline, Day 7 and 21 | 
| Percent Change From Baseline in S.Aureus CFU Count at Day 7, 14 and 21 Full Analysis Set | The S.Aureus CFU count is the number of CFU/cm2 for S.Aureus count in eczematous lesions. | Baseline, Day 7, Day 14 and Day 21 | 
| Percent Change From Baseline in S.Aureus CFU Count at Day 7, 14 and 21 Per Protocol Analysis Set | The S.Aureus CFU count is the number of CFU/cm2 for S.Aureus count in eczematous lesions. | Baseline, Day 7, Day 14 and Day 21 | 
| Percent Change From Baseline in KNS CFU Count at Day 7, 14 and 21 Full Analysis Set | The KNS CFU count is the number of CFU/cm2 for coagulase-negative staphylococcus count in eczematous lesions. | Baseline, Day 7, Day 14 and Day 21 | 
| Percent Change From Baseline in KNS CFU Count at Day 7, 14 and 21 Per Protocol Analysis Set | The KNS CFU count is the number of CFU/cm2 for coagulase-negative staphylococcus count in eczematous lesions. | Baseline, Day 7, Day 14 and Day 21 | 
| Percent Change From Baseline in Gram-positive Bacteria CFU Count at Day 7, 14 and 21 Full Analysis Set | The gram-positive CFU count is the number of CFU/cm2 for gram-positive bacteria count in eczematous lesions. | Baseline, Day 7, Day 14 and Day 21 | 
| Percent Change From Baseline in Gram-positive Bacteria CFU Count at Day 7, 14 and 21 Per Protocol Analysis Set | The gram-positive bacteria CFU count is the number of CFU/cm2 for gram-positive bacteria count in eczematous lesions. | Baseline, Day 7, Day 14 and Day 21 | 
| Change in Total Treated Eczema Area Full Analysis Set | Change from baseline (Day 1 morning) in total treated eczema area measured in cm2. | Baseline, Day 7, Day 14 and Day 21 | 
| Change in Total Treated Eczema Area Per Protocol Analysis Set | Change from baseline (Day 1 morning) in total treated eczema area measured in cm2. | Baseline, Day 7, Day 14 and Day 21 | 
| Change in Area of Microbial Counting Site Full Analysis Set | Change from baseline (Day 1 morning) in area of microbial counting site measured in cm2. | Baseline, Day 7, Day 14 and Day 21 | 
| Change in Area of Microbial Counting Site Per Protocol Analysis Set | Change from baseline (Day 1 morning) in area of microbial counting site measured in cm2. | Baseline, Day 7, Day 14 and Day 21 | 
| Erythema Eczema Area and Severity Index (EASI) Full Analysis Set | Evaluation of erythema on a scale 0-3 where 0=No symptoms, 1=Slight, 2=Moderate, 3=Severe | Day 7, Day 14 and Day 21 | 
| Erythema Eczema Area and Severity Index (EASI) Per Protocol Analysis Set | Evaluation of erythema on a scale 0-3 where 0=No symptoms, 1=Slight, 2=Moderate, 3=Severe | Day 7, Day 14 and Day 21 | 
| Excoriations Eczema Area and Severity Index (EASI) Full Analysis Set | Evaluation of excoriations on a scale 0-3 where 0=No symptoms, 1=Slight, 2=Moderate, 3=Severe | Day 7, Day 14 and Day 21 | 
| Excoriations Eczema Area and Severity Index (EASI) Per Protocol Analysis Set | Evaluation of excoriations on a scale 0-3 where 0=No symptoms, 1=Slight, 2=Moderate, 3=Severe | Day 7, Day 14 and Day 21 | 
| Infiltration Eczema Area and Severity Index (EASI) Full Analysis Set | Evaluation of infiltration on a scale 0-3 where 0=No symptoms, 1=Slight, 2=Moderate, 3=Severe | Day 7, Day 14 and Day 21 | 
| Infiltration Eczema Area and Severity Index (EASI) Per Protocol Analysis Set | Evaluation of infiltration on a scale 0-3 where 0=No symptoms, 1=Slight, 2=Moderate, 3=Severe | Day 7, Day 14 and Day 21 | 
| Lichenification Eczema Area and Severity Index (EASI) Full Analysis Set | Evaluation of lichenification on a scale 0-3 where 0=No symptoms, 1=Slight, 2=Moderate, 3=Severe | Day 7, Day 14 and Day 21 | 
| Lichenification Eczema Area and Severity Index (EASI) Per Protocol Analysis Set | Evaluation of lichenification on a scale 0-3 where 0=No symptoms, 1=Slight, 2=Moderate, 3=Severe | Day 7, Day 14 and Day 21 | 
| Investigator's Global Assessment of Eczema Change Full Analysis Set | Investigator's global assessment of eczema status since previous dose application on a categorical scale (worse, unchanged, improved) | Day 7, Day 14 and Day 21 | 
| Investigator's Global Assessment of Eczema Change Per Protocol Analysis Set | Investigator's global assessment of eczema status since previous dose application on a categorical scale (worse, unchanged, improved) | Day 7, Day 14 and Day 21 | 
| Change From Baseline in Visual Analog Scale of Itching (VASI) Full Analysis Set | The Visual Analog Scale of Itching (VASI), is the patient's assessment of itching on a 0-100 mm scale. 0 mm corresponds to no itching and 100 mm corresponds to maximum itching. Change from baseline is the change from day 1 morning. | Baseline, Day 7, Day 14 and Day 21 | 
| Change From Baseline in Visual Analog Scale of Itching (VASI) Per Protocol Analysis Set | The Visual Analog Scale of Itching (VASI), is the patient's assessment of itching on a 0-100 mm scale. 0 mm corresponds to no itching and 100 mm corresponds to maximum itching. Change from baseline is the change from day 1 morning. | Baseline, Day 7, Day 14 and Day 21 | 
| Patient's Global Assessment of Eczema Change Full Analysis Set | Patient's global assessment of eczema status since previous dose application on a categorical scale (worse, unchanged, improved) | Day 7, Day 14 and Day 21 | 
| Patient's Global Assessment of Eczema Change Per Protocol Analysis Set | Patient's global assessment of eczema status since previous dose application on a categorical scale (worse, unchanged, improved) | Day 7, Day 14 and Day 21 |