Back to resultsAnti-inflammatory Effects of Topical Erythromycin and Clindamycin in Acne Patients
Primary Purpose
Acne Vulgaris
Status
Recruiting
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Erythromycin 4% topical gel formulation
Clindamycin 1% topical lotion formulation
70% topical ethanol solution
Sponsored by
About this trial
This is an interventional treatment trial for Acne Vulgaris
Eligibility Criteria
Inclusion Criteria:
- Healthy male and female subjects, 18 to 45 years of age. The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease other than AV following a detailed medical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, virology and urinalysis;
- Mild to moderate inflammatory acne vulgaris on the face, ≥5 inflammatory lesions (papules and/or pustules), present at screening and baseline visit
- A maximum of 5 nodules present at screening and baseline visit
- Inflammatory acne present for at least 6 months
- Fitzpatrick skin type I-II (Caucasian)
- Able and willing to give written informed consent and to comply with the study restrictions.
- Willing to comply with 2x2mm facial skin punch biopsies
Exclusion Criteria:
- Severe acne where systemic treatment is needed
- Use of any topical (anti-acne) medication (prescription or OTC) within 2 weeks prior to baseline
- Use of any oral/systemic treatment for acne, including oral antibiotics, excluding OAC, within 4 weeks prior to baseline
- Use of systemic isotretinoin within 6 months prior to baseline
- History of pathological scar formation (keloid, hypertrophic scar)
- Known hypersensitivity to erythromycin or clindamycin, drugs of the same class, or any of their excipients.
- Known contact dermatitis reaction to any product
- Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment.
- Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year.
- Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening
- Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding
Sites / Locations
- Centre for Human Drug ResearchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Erythromycin 4%
Clindamycin 1%
ethanol solution
Arm Description
Erythromycin 4% topical gel formulation, BID, 4 weeks
Clindamycin 1% topical lotion formulation, BID, 4 weeks
70% topical ethanol solution, BID, 4 weeks
Outcomes
Primary Outcome Measures
Efficacy endpoint 1 - Change in lesion count
The inflammatory lesions include papules pustules and nodules/cysts. At screening and every study visit, the evaluator will count the inflammatory lesions separately by area on the face (forehead, right cheek, left cheek, chin and nose). All lesion counts during the treatment and follow-up period will be performed by a treatment-blinded evaluator
Efficacy endpoint 2 - Change in investigator Global Assessment acne (IGA)
Acne severity will be assessed at screening and every study visit by the Investigator Global Assessment for facial acne (clear, almost clear, mild, moderate, severe, very severe). This will be done by a treatment blinded evaluator.
Change in Patient Reported Outcome (PRO)
Pre-dose and at EOT patients will be asked how they would rate their acne that day using the subjective Patient Global Assessment (clear, almost clear, mild, moderate, severe, very severe)
Pharmacodynamic endpoints 1 - Change in Standardized facial photography by Canfield Visia and via selfie app
A standardized set of 3 facial photos (front, left, right) will be taken every study visit by Canfield Visia CR. Furthermore, patients will take daily selfies with a validated mobile app.
Pharmacodynamic endpoints 2 - Change in Sebum measurements by Sebumeter®
Sebum excretion will be measured every study visit by Sebumeter®. The measurement will be repeated for 3 times and the average will be used for the analysis.
Pharmacodynamic endpoints 3 - Change in Perfusion by Laser Speckle Contrast Imaging (LSCI)
Cutaneous microcirculation will be assessed using the laser speckle imager (LSCI; PeriCam PSI System, Perimed Jäfälla, Sweden). Measurements have to be performed in a temperature controlled room with a temperature around 22°C. The subject has to get accommodated to the room temperature for a minimum of 15 minutes prior to testing. After this, the speckle assessments can commence. Briefly, the subject will be resting for at least ten minutes before any measurements take place. A suitable area of the face will be identified. This area will be illuminated' by the laser and the response signal will be captured.
If no suitable area can be identified, the measurement will not be performed and data will be entered as missing.
Pharmacodynamic endpoints 4 - Change in Morphology by Optical Coherence Tomography (OCT)
Skin morphology will be assessed by optical coherence tomography at every study visit. Optical coherence tomography uses reflected light returning from skin tissue to create an image of the skin and 2 mm below the skin. The visualization can be done because different skin structures reflect light in a different way and can therefore be distinguished. Optical coherence tomography is similar to ultrasound however instead of sound it uses light refraction to visualize tissue.
Pharmacodynamic endpoints 5 - Change in Local skin biopsy biomarkers
Two-millimetre punch biopsies are taken at day 0 and day 28 from a papule or pustule. Moreover, at day 0 a biopsy will be taken from nonlesional non-facial skin (upper back) as healthy control. The biopsies will be placed in RNAlater medium directly after harvest of the biopsy and stored at 4°C. Biomarker sequencing will be performed by RNA extraction and quantitative PCR will be performed for a subset of immunomodulatory biomarkers (including but not limited to IL-1b, IL-1a, TNF-a IL-6, IL-12, IL-8, IL-10, IL-17, IFN-g).
Pharmacodynamic endpoints 6 - Change in Local skin surface biomarkers by TAP
Skin biomarkers will be measured pre-dose and after 7, 14, 21, 28, and 42 days by TAP (FibroTx, Estonia). TAP consists of a multiplex capture-antibody micro-array that is supported by a dermal adhesive bandage for fixture to skin. When TAP is applied to skin and left on for 20 minutes, the antibodies printed on the micro-array capture biomarkers from skin through immune recognition.
Biomarkers (IL-1a, IL-1b, TNF-a, IL-8, IL-6, IL-17) captured from skin by TAP are qualitatively and quantitatively analyzed by spot-ELISA by a specific TAP analyzer.
Pharmacodynamic endpoints 7 - Change in skin microbiota
The skin swab will be placed in a 2 ml lysis tube containing DNA/RNA shield to stabilize and preserve the DNA. The DNA extraction will be performed using adapted DNA extraction method based on the Zymo Research fecal DNA extraction methodology. The microbiome will be analyzed according to 16S rRNA gene sampling
Pharmacodynamic endpoints 8 - Change over time in p. acnes cultures
Swabs of predefined lesional (papule of pustule) and non-lesional skin will be taken with a sterile cotton swab. Colony numbers (colony forming units - CFU) and minimal inhibitory concentrations (MIC) will be reported. In addition, swabs of other lesions (i.e. nodules or scars) may be taken if applicable.
Moreover, in order to study P. acnes in the pilosebaceous unit a comedo extraction will be performed and the sebum will be cultured for P. acnes. Comedo extraction will be performed if applicable (i.e. if the patient has comedones).
Pharmacodynamic endpoints 9 - Change over time in faecal microbiota
Faecal samples will be collected at home. Subjects will use a 'faeces catcher' in their toilet and afterwards use a cotton swab to transfer a scoop of faeces to a 2 ml lysis tube (REF ZY-R1103, Zymo Research) containing DNA/RNA shield to stabilize and preserve the DNA.
Secondary Outcome Measures
Full Information
NCT ID
NCT03883269
First Posted
February 15, 2018
Last Updated
March 18, 2019
Sponsor
Centre for Human Drug Research, Netherlands
Collaborators
Maruho Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03883269
Brief Title
Anti-inflammatory Effects of Topical Erythromycin and Clindamycin in Acne Patients
Official Title
A Randomized, Placebo-controlled, Evaluator-blinded, Study to Assess the Anti-inflammatory Effects of Topical Erythromycin and Clindamycin in Patients With Inflammatory Facial Acne
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Recruiting
Study Start Date
March 20, 2018 (Actual)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre for Human Drug Research, Netherlands
Collaborators
Maruho Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The combined bacteriostatic and immunomodulatory effects of erythromycin and clindamycin will be explored. Treatment effects will be extensively characterized by conventional methods including lesion counts, global assessment scales and visual grading as well as state-of-the-art methodology, including multi-modal photo analysis, perfusion by laser speckle contrast imaging, analysis of local skin surface, biopsy biomarkers and skin microbiota. This extensive response profiling, combined with the mechanistic insights from concurrent in vitro and in vivo studies in healthy volunteer challenges, will increase the understanding of erythromycin's and clindamycin's effects in acne vulgaris.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acne Vulgaris
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A randomized, open-label, placebo-controlled, evaluator-blinded study.
Masking
Outcomes Assessor
Masking Description
Evaluator-blinded
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Erythromycin 4%
Arm Type
Experimental
Arm Description
Erythromycin 4% topical gel formulation, BID, 4 weeks
Arm Title
Clindamycin 1%
Arm Type
Experimental
Arm Description
Clindamycin 1% topical lotion formulation, BID, 4 weeks
Arm Title
ethanol solution
Arm Type
Placebo Comparator
Arm Description
70% topical ethanol solution, BID, 4 weeks
Intervention Type
Drug
Intervention Name(s)
Erythromycin 4% topical gel formulation
Intervention Description
Erythromycin 4% topical gel formulation, BID, 4 weeks
Intervention Type
Drug
Intervention Name(s)
Clindamycin 1% topical lotion formulation
Intervention Description
Clindamycin 1% topical lotion formulation, BID, 4 weeks
Intervention Type
Drug
Intervention Name(s)
70% topical ethanol solution
Intervention Description
70% topical ethanol solution, BID, 4 weeks
Primary Outcome Measure Information:
Title
Efficacy endpoint 1 - Change in lesion count
Description
The inflammatory lesions include papules pustules and nodules/cysts. At screening and every study visit, the evaluator will count the inflammatory lesions separately by area on the face (forehead, right cheek, left cheek, chin and nose). All lesion counts during the treatment and follow-up period will be performed by a treatment-blinded evaluator
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Efficacy endpoint 2 - Change in investigator Global Assessment acne (IGA)
Description
Acne severity will be assessed at screening and every study visit by the Investigator Global Assessment for facial acne (clear, almost clear, mild, moderate, severe, very severe). This will be done by a treatment blinded evaluator.
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Change in Patient Reported Outcome (PRO)
Description
Pre-dose and at EOT patients will be asked how they would rate their acne that day using the subjective Patient Global Assessment (clear, almost clear, mild, moderate, severe, very severe)
Time Frame
Day 0 and day 28
Title
Pharmacodynamic endpoints 1 - Change in Standardized facial photography by Canfield Visia and via selfie app
Description
A standardized set of 3 facial photos (front, left, right) will be taken every study visit by Canfield Visia CR. Furthermore, patients will take daily selfies with a validated mobile app.
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Pharmacodynamic endpoints 2 - Change in Sebum measurements by Sebumeter®
Description
Sebum excretion will be measured every study visit by Sebumeter®. The measurement will be repeated for 3 times and the average will be used for the analysis.
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Pharmacodynamic endpoints 3 - Change in Perfusion by Laser Speckle Contrast Imaging (LSCI)
Description
Cutaneous microcirculation will be assessed using the laser speckle imager (LSCI; PeriCam PSI System, Perimed Jäfälla, Sweden). Measurements have to be performed in a temperature controlled room with a temperature around 22°C. The subject has to get accommodated to the room temperature for a minimum of 15 minutes prior to testing. After this, the speckle assessments can commence. Briefly, the subject will be resting for at least ten minutes before any measurements take place. A suitable area of the face will be identified. This area will be illuminated' by the laser and the response signal will be captured.
If no suitable area can be identified, the measurement will not be performed and data will be entered as missing.
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Pharmacodynamic endpoints 4 - Change in Morphology by Optical Coherence Tomography (OCT)
Description
Skin morphology will be assessed by optical coherence tomography at every study visit. Optical coherence tomography uses reflected light returning from skin tissue to create an image of the skin and 2 mm below the skin. The visualization can be done because different skin structures reflect light in a different way and can therefore be distinguished. Optical coherence tomography is similar to ultrasound however instead of sound it uses light refraction to visualize tissue.
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Pharmacodynamic endpoints 5 - Change in Local skin biopsy biomarkers
Description
Two-millimetre punch biopsies are taken at day 0 and day 28 from a papule or pustule. Moreover, at day 0 a biopsy will be taken from nonlesional non-facial skin (upper back) as healthy control. The biopsies will be placed in RNAlater medium directly after harvest of the biopsy and stored at 4°C. Biomarker sequencing will be performed by RNA extraction and quantitative PCR will be performed for a subset of immunomodulatory biomarkers (including but not limited to IL-1b, IL-1a, TNF-a IL-6, IL-12, IL-8, IL-10, IL-17, IFN-g).
Time Frame
Day 0 and day 28
Title
Pharmacodynamic endpoints 6 - Change in Local skin surface biomarkers by TAP
Description
Skin biomarkers will be measured pre-dose and after 7, 14, 21, 28, and 42 days by TAP (FibroTx, Estonia). TAP consists of a multiplex capture-antibody micro-array that is supported by a dermal adhesive bandage for fixture to skin. When TAP is applied to skin and left on for 20 minutes, the antibodies printed on the micro-array capture biomarkers from skin through immune recognition.
Biomarkers (IL-1a, IL-1b, TNF-a, IL-8, IL-6, IL-17) captured from skin by TAP are qualitatively and quantitatively analyzed by spot-ELISA by a specific TAP analyzer.
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Pharmacodynamic endpoints 7 - Change in skin microbiota
Description
The skin swab will be placed in a 2 ml lysis tube containing DNA/RNA shield to stabilize and preserve the DNA. The DNA extraction will be performed using adapted DNA extraction method based on the Zymo Research fecal DNA extraction methodology. The microbiome will be analyzed according to 16S rRNA gene sampling
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Pharmacodynamic endpoints 8 - Change over time in p. acnes cultures
Description
Swabs of predefined lesional (papule of pustule) and non-lesional skin will be taken with a sterile cotton swab. Colony numbers (colony forming units - CFU) and minimal inhibitory concentrations (MIC) will be reported. In addition, swabs of other lesions (i.e. nodules or scars) may be taken if applicable.
Moreover, in order to study P. acnes in the pilosebaceous unit a comedo extraction will be performed and the sebum will be cultured for P. acnes. Comedo extraction will be performed if applicable (i.e. if the patient has comedones).
Time Frame
Day 0, day 7, day 14, day 21, day 28 and day 42
Title
Pharmacodynamic endpoints 9 - Change over time in faecal microbiota
Description
Faecal samples will be collected at home. Subjects will use a 'faeces catcher' in their toilet and afterwards use a cotton swab to transfer a scoop of faeces to a 2 ml lysis tube (REF ZY-R1103, Zymo Research) containing DNA/RNA shield to stabilize and preserve the DNA.
Time Frame
before day 0 and after day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy male and female subjects, 18 to 45 years of age. The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease other than AV following a detailed medical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, virology and urinalysis;
Mild to moderate inflammatory acne vulgaris on the face, ≥5 inflammatory lesions (papules and/or pustules), present at screening and baseline visit
A maximum of 5 nodules present at screening and baseline visit
Inflammatory acne present for at least 6 months
Fitzpatrick skin type I-II (Caucasian)
Able and willing to give written informed consent and to comply with the study restrictions.
Willing to comply with 2x2mm facial skin punch biopsies
Exclusion Criteria:
Severe acne where systemic treatment is needed
Use of any topical (anti-acne) medication (prescription or OTC) within 2 weeks prior to baseline
Use of any oral/systemic treatment for acne, including oral antibiotics, excluding OAC, within 4 weeks prior to baseline
Use of systemic isotretinoin within 6 months prior to baseline
History of pathological scar formation (keloid, hypertrophic scar)
Known hypersensitivity to erythromycin or clindamycin, drugs of the same class, or any of their excipients.
Known contact dermatitis reaction to any product
Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment.
Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year.
Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening
Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Robert Rissmann, PharmD, PhD
Phone
+31 71 5246 400
Email
clintrials@chdr.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Diana Noort
Phone
+31 71 5246 400
Email
clintrials@chdr.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Rissmann, PharmD, PhD
Organizational Affiliation
CHDR
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Human Drug Research
City
Leiden
ZIP/Postal Code
2333 CL
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Rissmann, PharmD, PhD
Phone
+31 71 5246 400
Email
clintrials@chdr.nl
First Name & Middle Initial & Last Name & Degree
Diana Noort
Phone
+31 71 5246 400
Email
clintrials@chdr.nl
12. IPD Sharing Statement
Learn more about this trial
Anti-inflammatory Effects of Topical Erythromycin and Clindamycin in Acne Patients
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