Healthy
Conditions
Keywords
volunteers
Brief summary
Exploratory, mono-center, randomized, intra-individual, controlled trial involving healthy volunteers to compare the effect on MAL penetration into the skin following various mechanical penetration enhancement techniques.
Detailed description
At baseline, each mini-zone was selected and randomly assigned to a pretreatment: 3 zones with microneedling Dermaroller®, 3 zones with ablative fractional CO2 Laser, and 3 zones with no pretreatment. After performing pretreatment, MAL cream was applied on the 6 assigned mini-zones for 3 hours incubation. Each condition was tested with and without occlusion. The three mini-zones with no product applied were used to perform biophysics measures.
Interventions
OTHERocclusive bandage
DEVICEablative fractional CO2 laser pretreatment
DEVICEMicroneedles pretreatment
DRUGMETVIXIA Cream
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female of non childbearing potential, who is at least 18 years of age or older at screening visit. * The subject has a skin phototype of I to III on Fitzpatrick's scale (Fitzpatrick et al., 1993) at screening visit. * Subject should have 9 mini zone areas on the back that will be able to receive pre-treatments according to protocol. (checked at Screening visit, and assigned at Baseline visit) * Female of non childbearing potential (postmenopausal \[absence of menstrual bleeding for 1 year prior to screening visit, without any other medical reason\], hysterectomy or bilateral oophorectomy).
Exclusion criteria
* Subject with porphyria, * Subject with past history of skin cancer, or current clinical diagnosis of other skin disease (including non-melanoma skin cancer), or tattoos, or cheloid and hypertrophic scars on the test zones, which, in the opinion of the investigator, might interfere with the interpretation of the clinical results, * Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with the interpretation of the clinical trial results, and/or put the subject at significant risk (according to Investigator's judgment) if he/she participates in the clinical trial. * Known or suspected allergies or sensitivities to any components of any of the study drugs (see Product label). * The subject has received, applied or taken some specific treatments within specified time frame prior to the baseline visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Fluorescence Levels Measured by Spectrofluorometer Probe at Timepoint T0 (Before Metvixia® Application) | At T0 (before Metvixia® application ) | Spectrofluorometer probe in contact with skin was used to measure surface, deeper skin fluorescence, using different photoactive Protoporphyrin IX (PpIX) excitation wavelengths. Fluorescence measurements were used to estimate quantity of PpIX in skin, corresponding with degree of Metvixia® skin penetration. Three measurements were taken at different locations within each mini-zone at 5 time points: T0 (before Metvixia® application), and 30 minutes,1 hour(hr),2hr, 3hr after Metvixia® application (immediately after cream removal at 3hr time point). Fluorescence data obtained using spectrofluorometer probe for two wavelengths that is, 405 nanometer(nm) measured fluorescence on skin surface, 632nm measured fluorescence in deep skin reported in this outcome measure. Maximal value was used to characterize Peak Effect, time point of this value was used to characterize Time to Peak. Negative values meant there was no longer fluorescence, it was corrected measurement derived from fluorescence. |
| Mean Fluorescence Levels Measured by Spectrofluorometer Probe at Timepoint T30 (30 Minutes After Metvixia® Application) | At T0+ 30 minutes (30 minutes after Metvixia® application) | A spectrofluorometer probe in contact with the skin was used to measure surface, as well as deeper skin fluorescence, using different Protoporphyrin IX (PpIX) excitation wavelengths. Fluorescence measurements were used to estimate the quantity of PpIX in the skin, corresponding with the degree of Metvixia® skin penetration. Three measurements were taken at different locations within each mini-zone at 5 time points: T0 (before Metvixia® application), and 30 minutes, 1 hour, 2 hours and 3 hours after Metvixia® application (immediately after cream removal at the 3 hour time point). Fluorescence data obtained using the spectrofluorometer probe for the two wavelengths that is, 405 nm measured fluorescence on skin surface and 632 nm measured fluorescence in deep skin were reported in this outcome measure. The maximal value was used to characterize the Peak Effect, and the time point of this value was used to characterize the Time to Peak. |
| Mean Fluorescence Levels Measured by Spectrofluorometer Probe at Timepoint 1 Hour (After Metvixia® Application) | At 1 Hour (After Metvixia® Application) | A spectrofluorometer probe in contact with the skin was used to measure surface, as well as deeper skin fluorescence, using different Protoporphyrin IX (PpIX) excitation wavelengths. Fluorescence measurements were used to estimate the quantity of PpIX in the skin, corresponding with the degree of Metvixia® skin penetration. Three measurements were taken at different locations within each mini-zone at 5 time points: T0 (before Metvixia® application), and 30 minutes, 1 hour, 2 hours and 3 hours after Metvixia® application (immediately after cream removal at the 3 hour time point). Fluorescence data obtained using the spectrofluorometer probe for the two wavelengths that is, 405 nm measured fluorescence on skin surface and 632 nm measured fluorescence in deep skin were reported in this outcome measure. The maximal value was used to characterize the Peak Effect, and the time point of this value was used to characterize the Time to Peak. |
| Mean Fluorescence Levels Measured by Spectrofluorometer Probe at Timepoint 2 Hour (After Metvixia® Application) | At T0+ 2 Hour (After Metvixia® Application) | A spectrofluorometer probe in contact with the skin was used to measure surface, as well as deeper skin fluorescence, using different Protoporphyrin IX (PpIX) excitation wavelengths. Fluorescence measurements were used to estimate the quantity of PpIX in the skin, corresponding with the degree of Metvixia® skin penetration. Three measurements were taken at different locations within each mini-zone at 5 time points: T0 (before Metvixia® application), and 30 minutes, 1 hour, 2 hours and 3 hours after Metvixia® application (immediately after cream removal at the 3 hour time point). Fluorescence data obtained using the spectrofluorometer probe for the two wavelengths that is, 405 nm measured fluorescence on skin surface and 632 nm measured fluorescence in deep skin were reported in this outcome measure. The maximal value was used to characterize the Peak Effect, and the time point of this value was used to characterize the Time to Peak. |
| Mean Fluorescence Levels Measured by Spectrofluorometer Probe at Timepoint 3 Hour (After Metvixia® Application) | At 3 Hour (After Metvixia® Application) | A spectrofluorometer probe in contact with the skin was used to measure surface, as well as deeper skin fluorescence, using different Protoporphyrin IX (PpIX) excitation wavelengths. Fluorescence measurements were used to estimate the quantity of PpIX in the skin, corresponding with the degree of Metvixia® skin penetration. Three measurements were taken at different locations within each mini-zone at 5 time points: T0 (before Metvixia® application), and 30 minutes, 1 hour, 2 hours and 3 hours after Metvixia® application (immediately after cream removal at the 3 hour time point). Fluorescence data obtained using the spectrofluorometer probe for the two wavelengths that is, 405 nm measured fluorescence on skin surface and 632 nm measured fluorescence in deep skin were reported in this outcome measure. The maximal value was used to characterize the Peak Effect, and the time point of this value was used to characterize the Time to Peak. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Fluorescence Levels Measured by Mini-zone Photo Camera Device at Timepoint T0 (Before Metvixia® Application) and 3 Hours (After Metvixia® Application and Immediately After Cream Removal) | At T0 (Before Metvixia® application) and 3 Hours (After Metvixia® Application and Immediately After Cream Removal) | A mini-zone camera device was used to measure skin surface fluorescence at a single excitation wavelength 405 nm before, and after Metvixia® application. Fluorescence measurements were used to estimate the quantity of PpIX in the skin, corresponding with the degree of Metvixia® skin penetration. This device uses the classical excitation wavelength: 405nm, was designed for Actinic Keratoses (AK) and had fluorescence references included. Pictures were performed for each zone before pre-treatment and after cream removal at visit 2 (V2) for documentation of fluorescence. |
| Fluorescence Levels Measured by Trans-Epidermal Water Loss (TEWL) at Timepoint T0 (Before Metvixia® Application) | At timepoint T0 (Before Metvixia® application) | TEWL evaluated the efficiency of the skin water barrier, which correlates with the degree of damage to the barrier function of the stratum corneum. TEWL was assessed on the mini-zones that were not treated with Metvixia®. It was measured in Grams of Water Per Square Meter Per Hour (g/m\^2/hr). |
Participant flow
Recruitment details
The study was conducted from 27 Feb 2014 to 09 May 2014.
Pre-assignment details
Study drug was tested under 3 different conditions (2 pre-treatments-using Homecare Dermaroller and CO2 Ablative Fractional Laser, and normal skin) each of which was tested under occlusion and without occlusion for a total of 6 mini-zones applied. In addition, 3 mini-zones were pre-treated but no product was applied. In total, all these conditions was tested on 9 different mini zones (at back) of 2\*2 centimeters (cm) area (4 cm\^2) on each participant.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41.5 Years STANDARD_DEVIATION 9.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
| Skin phototype II | 2 Participants |
| Skin phototype III | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 2 / 10 | 1 / 10 | 1 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
None listed