Clinical trial NCT03883269: 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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acne Vulgaris
Lead sponsor: Centre for Human Drug Research, Netherlands
Sponsor class: OTHER
Collaborators: name: Maruho Co., Ltd.
First posted: 2019-03-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, open-label, placebo-controlled, evaluator-blinded study.
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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;
2. Mild to moderate inflammatory acne vulgaris on the face, ≥5 inflammatory lesions (papules and/or pustules), present at screening and baseline visit
3. A maximum of 5 nodules present at screening and baseline visit
4. Inflammatory acne present for at least 6 months
5. Fitzpatrick skin type I-II (Caucasian)
6. Able and willing to give written informed consent and to comply with the study restrictions.
7. Willing to comply with 2x2mm facial skin punch biopsies

Exclusion Criteria:

1. Severe acne where systemic treatment is needed
2. Use of any topical (anti-acne) medication (prescription or OTC) within 2 weeks prior to baseline
3. Use of any oral/systemic treatment for acne, including oral antibiotics, excluding OAC, within 4 weeks prior to baseline
4. Use of systemic isotretinoin within 6 months prior to baseline
5. History of pathological scar formation (keloid, hypertrophic scar)
6. Known hypersensitivity to erythromycin or clindamycin, drugs of the same class, or any of their excipients.
7. Known contact dermatitis reaction to any product
8. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment.
9. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year.
10. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening
11. Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding

Primary outcomes:
measure: Efficacy endpoint 1 - Change in lesion count
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Efficacy endpoint 2 - Change in investigator Global Assessment acne (IGA)
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Change in Patient Reported Outcome (PRO)
timeFrame: Day 0 and day 28
measure: Pharmacodynamic endpoints 1 - Change in Standardized facial photography by Canfield Visia and via selfie app
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Pharmacodynamic endpoints 2 - Change in Sebum measurements by Sebumeter®
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Pharmacodynamic endpoints 3 - Change in Perfusion by Laser Speckle Contrast Imaging (LSCI)
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Pharmacodynamic endpoints 4 - Change in Morphology by Optical Coherence Tomography (OCT)
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Pharmacodynamic endpoints 5 - Change in Local skin biopsy biomarkers
timeFrame: Day 0 and day 28
measure: Pharmacodynamic endpoints 6 - Change in Local skin surface biomarkers by TAP
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Pharmacodynamic endpoints 7 - Change in skin microbiota
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Pharmacodynamic endpoints 8 - Change over time in p. acnes cultures
timeFrame: Day 0, day 7, day 14, day 21, day 28 and day 42
measure: Pharmacodynamic endpoints 9 - Change over time in faecal microbiota
timeFrame: before day 0 and after day 28
Secondary outcomes:
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
Study officials:
affiliation: CHDR
name: Robert Rissmann, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References: