XYON Health Clinical Studies: SiloxysSystem™ Gel

Background on finasteride
Oral finasteride has been used to treat androgenetic alopecia (also known as male pattern hair loss) for over 20 years. This medication targets the enzyme 5-alpha reductase, which is involved in the production of the male sex steroid hormone dihydrotestosterone (DHT). The binding of DHT to hair follicle cells is recognized as the cause of hair follicle miniaturization and ultimately, premature hair loss in susceptible individuals (Cranwell & Sinclair, 2016).

Clinical and real-world data have shown that finasteride is effective at reducing levels of DHT, slowing or even halting the progression of hair loss and encouraging hair regrowth (Zito et al., 2022). However, as with most medications, it may come with side effects.

The side effect profile of oral finasteride has been extensively studied. Current data suggests that the majority of side effects are sexual (e.g. erectile dysfunction, decreased libido, decreased ejaculatory volume). However, psychiatric and mood changes have also been reported (Divicarro et al., 2020).

In many cases, these side effects resolve over time. However, in a small subset of individuals presenting with post-finasteride syndrome, side effects can persist even after discontinuing treatment (Pereira & Coelho, 2020). 

In our tests, we used a small human skin sample as the membrane to mimic the body’s natural barrier. Three different gel carriers were compared: (1) SiloxysSystem™ Gel, (2) a standard carbopol-based gel and (3) a standard liposomal gel. Each gel was individually combined with the same amount of finasteride (2.5% by weight).

The gels were then individually introduced into the donor chamber of the Franz Cell. Permeation (absorption) of finasteride through the skin membrane was measured over the course of 24 hours. The amount of drug in these samples was further quantified using liquid chromatography and mass spectroscopy, which are two standard analytical techniques.

Franz cell results: measuring skin absorption of finasteride

The amount of finasteride that permeated the skin membrane at the end of 24 hours was found to be 0.66 ± 0.24 mcg/cm2 with SiloxysSystem™ Gel, 1.55 ± 0.06 mcg/cm2 with the carbopol-based gel and 4.11 ± 1.50 mcg/cm2 with the standard liposomal gel. A calculation of estimated plasma steady state concentrations was also performed.

What is steady state?
Steady state refers to the point at which the quantity of a medication being eliminated from the body equals the rate at which the same quantity of medication enters the body. This is generally considered the point at which the mediation will have its maximum effect. For some medications, steady state may be achieved within days of starting treatment. For others, this process may take weeks.

Using a standard reference value for systemic clearance (rate of elimination) for oral finasteride, maximum plasma concentrations of the medication were obtained for each of the three gel carriers.

These concentrations were found to be 0.49 ng/mL, 0.74 ng/mL and 2.69 ng/mL for SiloxysSystem™ Gel, the carbopol-based gel and standard liposomal gel, respectively.

Interpretations of Franz cell data
When administered with SiloxysSystem™ Gel technology, permeation of finasteride across the skin was approximately 6-7 times less than that of a typical liposomal carrier over 24 hours. Additionally, in the case of the standard liposomal gel, a bolus effect (delivery of a single large dose of medication over a short time interval) was observed within the first 8 hours of introduction into the donor chamber.

In comparison, when SiloxysSystem™ Gel was used to deliver 2.5% finasteride, a near constant rate of drug delivery was achieved over a 24 hour period. This demonstrates a highly desirable “controlled release” kinetic pattern.

Furthermore, estimations of plasma steady state concentrations of finasteride showed that SiloxysSystem™ Gel technology is associated with the lowest levels of finasteride (0.49 ng/mL) among the three carriers tested. For reference, the plasma steady state concentration of oral finasteride 1 mg (taken once daily) is 9.2 ng/mL, approximately 19 times higher.

This data suggests that when used as a carrier, SiloxysSystem™ Gel can reduce permeation of a medication such as finasteride. The gel’s barrier-forming properties allow for slow and steady release of the medication that is not observed in either the standard carbopol or liposomal gels. This is a highly desirable attribute to have in a delivery system for medication.

PK study: overview

PK studies provide further insight into a medicine’s ADME (absorption, distribution, metabolism and excretion) properties. To assess how much of a medication such as finasteride has entered and remains in the systemic circulation, a series of blood draws is performed on study participants after administration of the medication.

This is done in order to measure the concentration of the medication in the circulation at different time points over a 24-hour period and provides a more accurate representation of the exposure of the body to a medication, compared to a single blood draw at one time point.

Methods
A PK study was performed to assess the effect of administering finasteride using SiloxysSystem™ Gel technology on:

1. How much finasteride is absorbed and remains in the bloodstream and
2. Blood levels of DHT.

Study eligibility
In order to be eligible for this clinical study, participants needed to be diagnosed with male pattern hair loss. The degree of hair loss was assessed using the Hamilton-Norwood Scale and individuals with more advanced hair loss were included.

Participants were ensured to not be taking finasteride at the time of the study and could not have taken finasteride in the month prior to enrollment. Furthermore, they could not have taken any anabolic steroids, antiandrogen therapies or testosterone replacement in the past 6 months. Scalp skin had to be intact and healthy. Concomitant use of any other topical medications or investigative drug products was not permitted.

Study candidates who met the above criteria were informed of the risks and potential benefits of the treatment. A consent form was dated and signed by each participant prior to voluntarily participating in this study. Each participant was counselled on possible side effects of finasteride and instructed to inform the physician if they experienced any untoward reaction(s) to the medication.

Study procedures
First, a pre-treatment blood draw was performed to obtain a baseline DHT measurement for each study participant. This was repeated two more times at hour 1 and hour 4 after the first blood draw in order to allow each participant to act as his own control.

Immediately following the third DHT measurement at hour 4, study participants applied 2.5% Topical Finasteride with SiloxysSystem™ Gel as instructed by the study investigator, Dr. Victor Hasson. Participants were asked to continue once daily application of the gel every morning for one month. This was to ensure that the drug would reach steady state before the next round of blood draws.

After one month of home treatment with 2.5% Topical Finasteride with SiloxysSystem™ Gel, study participants were brought back to the clinic. A pre-dose blood draw was performed on each participant prior to their morning application (this is known as a trough level).

Following dosing, additional blood draws were performed at hours 1, 2, 4, 8 and 24 to assess post-dose finasteride concentrations, as well as the effect on serum DHT levels. Participants were asked to abstain from strenuous exercise and sexual activity in the 2 days prior to testing to minimize the possibility of transient DHT elevations interfering with measurements.

Interpreting PK test data:

7 participants were enrolled into the study. Application of 2.5% Topical Finasteride with SiloxysSystem™ Gel resulted in a mean plasma concentration of finasteride of 0.74 ± 0.34 ng/mL (Figure 2). This is a markedly lower level of circulating finasteride compared to the reference value of 9.20 ± 2.63 ng/mL seen with the oral pill. Additionally, once steady state was achieved, there was no post-dose spike in finasteride levels over a 24 hour period (Figure 3).

It was also noted that the effect of topical finasteride on serum DHT levels was minimized with SiloxysSystem™ Gel technology. Compared to oral finasteride, suppression of serum DHT levels decreased by 55% (-31 ± 21% with the topical vs. -70 ± 9% with the oral) (Figure 4) and mean plasma DHT concentrations remained fairly constant over the course of 24 hours (Figure 5).