Double Blinded Randomized Placebo Controlled Clinical Study for the Evaluation of the Efficacy of One Active Ingredient Incorporated Into a Food Supplement
Phase: NA
Conditions: Spot Pigmented, Wrinkle
Sponsor: Mibelle Group Biochemistry

 
Mod.099.02 
 
 
 
 
 
Official Title of the study:  
DOUBLE BLINDED RANDOMIZED PLACEBO CONTROLLED 
CLINICAL STUDY FOR THE EVALUATION OF THE EFFICACY OF 
ONE ACTIVE INGREDIENT INCORPORATED INTO A FOOD 
SUPPLEMENT 
 
 
NCT number (not yet assigned) 
 
Date of the document: 08/03/2024 

 
Mod.099.02 
 
CIP n 
P016C23_v02 
Study beginning 
date: 
21/06/2023 
Study conclusion/ 
suspension date: 
08/03/2024 
Title 
Double blinded randomized placebo controlled clinical study for the evaluation of the 
efficacy of one active ingredient incorporated into a food supplement 
 
Study Protocol 
The primary aim of this in vivo clinical study is to evaluate the depigmenting effect of an 
active ingredient incorporated into a food supplement through the evaluation of the 
melanin variation parameter, assessed with the equipment Antera 3D (Miravex, 
Ireland), after 28 consecutive days of food supplement’s once-daily intake, in 
comparison with the baseline and a placebo. 
The secondary objective of this study is to evaluate in vivo the depigmenting effect of 
the same active ingredient incorporated into a food supplement through the 
evaluation of the melanin variation parameter, assessed with the equipment Antera 3D 
(Miravex, Ireland), after 56 and 84 consecutive days of food supplement’s once-daily 
intake. 
Other goals of this clinical study are to evaluate in vivo the effect of the same active 
ingredient incorporated into a food supplement, after 28, 56 and 84 consecutive days 
of a once-daily intake, in comparison with the baseline and a placebo (1) on skin 
whitening/brightening through the evaluation of the L* parameter, assessed with the 
equipment Antera 3D (Miravex, Ireland), (2) on the skin colour homogeneity through 
the measurement of the ITAº (Individual Typology Angle) parameter, assessed with the 
equipment Colorimeter® CL400, (3) on the skin tone evenness through the 
measurement of the standard deviation of the skin colour, assessed with the equipment 
Colorimeter® CL400, (4) on the skin density of the dermis, measured with the equipment 
Episcan 20 MHz (Longport Inc, United States), (5) on skin hydration assessed through 
capacitance measurements with the equipment Corneometer® CM825, (6) on the skin 
firmness, skin overall elasticity and skin total deformation measured with the equipment 
Cutometer® SEM 575 (Courage+Khazaka electronic GmbH, Germany), and (7) on skin 
radiance through clinical evaluation performed by an expert. 
It is also objective of this clinical study to evaluate (8) subjects’ tolerance, acceptability, 
perception of efficacy and future use/purchase intention towards the food 
supplements by filling out a subjective evaluation questionnaire after 28, 56 and 84 
consecutive days of food supplement’s once-daily intake. 
Study Protocol, Statistical Analysis Plan and Results of the Study 

 
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To perform this study, 110 female healthy subjects, with ages between 25 and 60 years 
old, presenting mild to moderate fine lines and wrinkles, mild to moderate skin spots 
and phototype III to V, according to the Fitzpatrick phototyping scale, are enrolled. The 
subjects are randomly divided in two groups, the test group, taking the active 
ingredient incorporated into a food supplement and the placebo group, taking the 
food supplement without the active ingredient. 
A 2 weeks washout period is performed, if subject has taken any kind of supplements 
(Vitamins, antioxidants, nutraceuticals) before the beginning of the study. In this period 
subjects cannot use any kind of supplements. 
Each subject shall take 1 capsule of the food supplement per day, with lunch, for 84 
consecutive days. 
 
Statistical Analysis Plan 
A descriptive statistical analysis of the skin depigmenting, skin whitening/brightening, 
skin density, skin hydration, skin firmness, skin overall elasticity, skin total deformation and 
skin radiance results are performed for each group at each evaluation time-point, 
including the calculation of mean, standard deviation, and graphic representations. 
Normality tests (Shapiro-Wilk test) are performed in order to assure normal distribution of 
the objective data obtained. 
If normal distribution of the data is verified: 
- paired-sample t-tests are applied to compare the results obtained for each 
parameter before (t0) versus after 28 (t1), 56 (t2) and 84 (t3) days of each food 
supplement’s intake; 
- independent t-tests are applied to compare the differences to baseline obtained 
with the investigational product versus the ones obtained with the comparator 
product at each time-point of evaluation (t1, t2 and t3). 
For non-normal distributions non-parametric tests are used: 
- Wilcoxon-tests are applied to compare the results obtained for each parameter 
before (t0) versus after 28 (t1), 56 (t2) and 84 (t3) days of each food supplement’s 
intake; 
- Mann-Whitney tests are applied to compare the differences to baseline obtained 
with the investigational product versus the ones obtained with the comparator 
product at each time-point of evaluation (t1, t2 and t3). 
The significance value is established at 0.05 and at a power of 0.95. 
Descriptive statistics of the subjective evaluation is performed at each time-point of 
evaluation with the calculation of number and percentage of subjects responding to 
each answer option and the results presented in graphic representations. 
 

 
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Results 
The most relevant results that can be concluded from this study are: 
 
Investigational product 
Comparator product placebo 
Skin  
depigmenting 
The product showed a skin depigmenting effect 
after 84 days of products’ intake, in comparison to 
the baseline. After 28 and 56 days of products’ 
intake, no improvement was observed. 
No improvement in the skin depigmenting was 
observed after 28, 56 and 84 days of products’ 
intake, in comparison to the baseline. 
The investigational product has no effect on the skin depigmenting, in comparison to the placebo. 
− 
28.00%, 52.08% and 61.22% of the subjects agreed to strongly agreed that their skin is with less 
hyperpigmentation spots 28, 56 and 84 days after the daily intake of the investigational product, 
respectively. 
− 
26.53%, 55.10% and 53.07% of the subjects agreed to strongly agreed that their skin is with less 
hyperpigmentation spots 28, 56 and 84 days after the daily intake of the placebo, respectively. 
Skin 
whitening/ 
brightening 
The product demonstrated a skin whitening/ 
lightening effect after 56 and 84 days of products’ 
intake, in comparison to the baseline. After 28 days 
of products’ intake, no improvement was observed. 
The product demonstrated a skin whitening/ 
lightening effect after 56 and 84 days of products’ 
intake. After 28 days of products’ intake, no 
improvement was observed. 
The investigational product has a skin whitening/brightening effect, in comparison to the placebo, after 84 
days of products’ intake. 
− 
32.00%, 60.42% and 55.10% of the subjects agreed to strongly agreed that their skin had a luminous 
effect 28, 56 and 84 days after the daily intake of the investigational product, respectively. 
− 
32.65%, 51.02% and 57.14% of the subjects agreed to strongly agreed that their skin had a luminous 
effect 28, 56 and 84 days after the daily intake of the placebo, respectively. 
Skin colour 
The product revealed a skin tone lightening effect 
after 28, 56 and 84 consecutive days of products’ 
intake, in comparison to the baseline. 
The product revealed a skin tone lightening effect 
after 56 days of products’ intake, in comparison to 
the baseline. After 28 and 84 days of products’ 
intake, no improvement was observed.  
The investigational product has an almost statistically significant improvement in the skin tone lightening, in 
comparison to the placebo, after 84 days of products’ intake, supporting the skin whitening/lightening 
effect observed previously. 
Skin tone 
evenness 
No improvement in the skin tone evenness was 
observed after 28, 56 and 84 days of products’ 
intake. 
No improvement in the skin tone evenness was 
observed after 28, 56 and 84 days of products’ 
intake. 
The investigational product has no effect on the skin tone evenness, in comparison to the placebo. 
− 
32.00%, 60.42% and 67.34% of the subjects agreed to strongly agreed that their skin is with more 
homogeneous skin tone 28, 56 and 84 days after the daily intake of the investigational product, 
respectively. 
− 
32.65%, 59.18% and 59.18% of the subjects agreed to strongly agreed that their skin is with more 
homogeneous skin tone 28, 56 and 84 days after the daily intake of the placebo, respectively. 
Skin density 
No improvement in the density of the dermis was 
observed after 28, 56 and 84 days of products’ 
No improvement in the density of the dermis was 
observed after 28, 56 and 84 days of products’ 

 
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intake, in comparison to the baseline. Instead, a 
significant decrease was observed. 
intake, in comparison to the baseline. Instead, a 
significant decrease was observed. 
The investigational product has no effect on the density of the dermis, in comparison to the placebo. 
− 
14.00%, 33.33% and 32.65% of the subjects agreed to strongly agreed that their skin is denser 28, 56 
and 84 days after the daily intake of the investigational product, respectively. 
− 
22.45%, 36.73% and 38.77% of the subjects agreed to strongly agreed that their skin is denser 28, 56 
and 84 days after the daily intake of the placebo, respectively. 
Skin hydration 
No improvement in the skin hydration was observed 
after 28, 56 and 84 days of products’ intake, in 
comparison to the baseline. 
No improvement in the skin hydration was observed 
after 28, 56 and 84 days of products’ intake, in 
comparison to the baseline. Instead, a decrease 
was observed after 84 days of products’ intake. 
The investigational product has no effect on the skin hydration, in comparison to the placebo. 
− 
50.00%, 60.42% and 61.23% and 36.73% of the subjects agreed to strongly agreed that their skin is 
more hydrated 28, 56 and 84 days after the daily intake of the investigational product, 
respectively. 
− 
36.73%, 51.02% and 69.39% of the subjects agreed to strongly agreed that their skin is more 
hydrated 28, 56 and 84 days after the daily intake of the Placebo, respectively. 
Skin total 
deformation 
No improvement in skin total deformation was 
observed after 28, 56 and 84 days of products’ 
intake, in comparison to the baseline. Instead, an 
increase was observed after 84 days of products’ 
intake. 
No improvement in skin total deformation was 
observed after 28, 56 and 84 days of products’ 
intake, in comparison to the baseline.  Instead, an 
increase was observed after 84 days of products’ 
intake. 
The investigational product has no effect on the skin total deformation, in comparison to the placebo. 
Skin overall 
elasticity 
No improvement in skin overall elasticity was 
observed after 28, 56 and 84 days of products’ 
intake, in comparison to the baseline. 
The product showed to increase the skin overall 
elasticity after 84 days of products’ intake, in 
comparison to the baseline. After 28 and 56 
consecutive 
days 
of 
products’ 
intake, 
no 
improvement was observed. 
The investigational product has no effect on skin overall elasticity, in comparison to the placebo. 
Skin firmness 
No improvement in skin firmness was observed after 
28, 56 and 84 days of products’ intake, in 
comparison to the baseline. 
The product showed to increase the skin firmness 
after 84 days of products’ intake, in comparison to 
the baseline. After 28 and 56 consecutive days of 
products’ intake, no improvement was observed. 
The investigational product has no effect on skin firmness, in comparison to the placebo.). 
− 
18.00%, 37.50% and 42.86% of the subjects agreed to strongly agreed that their skin is firmer 28, 56 
and 84 days after the daily intake of the investigational product, respectively. 
− 
28.57%, 40.81% and 42.85% of the subjects agreed to strongly agreed that their skin is firmer 28, 56 
and 84 days after the daily intake of the placebo, respectively. 
Skin radiance 
The product demonstrated a skin radiance effect 
after 28, 56 and 84 days of products’ intake, in 
comparison to the baseline. 
The product demonstrated a skin radiance effect 
after 28, 56 and 84 days of products’ intake, in 
comparison to the baseline. 

 
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The investigational product has no effect on the radiance condition of the subject’s skin, in comparison to 
the placebo. 
 
Additionally, the following results were obtained from the subjects’ subjective 
evaluation: 
• 
In a general way, 73.47% and 63.26% of the subjects evaluated the 
investigational product and placebo as good to very good, respectively, after 
84 days of daily intake; 
• 
92% and 91.84% of the subjects agreed to strongly agreed that it was practical 
to include the investigational product and placebo in their daily routine, 
respectively; 
• 
75.51% and 67.35% of the subjects agreed to strongly agreed that their skin is 
with better appearance 84 days after the daily intake of the investigational 
product and placebo, respectively; 
• 
89.80% and 75.51% of the subjects agreed to strongly agreed that they would 
like to continue taking the supplement and placebo, respectively; 
• 
89.80% and 77.56% of the subjects agreed to strongly agreed that they would 
recommend the supplement and placebo to a friend, respectively. 
 
The product was in general well tolerated by the subjects with no subjects reporting any 
serious adverse events. However, five subjects reported mild discomforts, which were 
resolved during the study. 
 
The benefits of the investigation superposed the risks, as the efficacy degree of the 
products was assessed and no adverse events were observed. 
 
The principal hypothesis of this clinical study is that the melanin variation parameters will 
decrease at least 7.02% after 28 days of the intake of the investigational product, 
compared to the placebo. This hypothesis was not verified with this clinical 
investigation.  
 
In conclusion, the investigational product showed to have a skin whitening/brightening 
effect, in comparison to the placebo, after 84 days of products’ intake, while no effects 
were observed for the skin depigmenting, skin tone evenness, skin density, skin 
hydration, skin total deformation, skin overall elasticity, skin firmness and skin radiance, 
in comparison to the placebo, after 28, 56 and 84 consecutive days of products’ intake.