Frontage Clinical in Hackensack, NJ is conducting a research study to evaluate the safety of an investigational topical gel medication for moderate to severe facial redness associated with ROSACEA.

All qualified participants will receive at no cost evaluations by a certified physician, investigational gel medication and compensation for participating.

Must be 18 years or older and have been diagnosed with Rosacea.

Must contact Recruiting Department at (201) 678-0288 for further information

A reasonable guess is that this trial is for the Oxymetazoline based V-101 product from Vicept Therapeutics or the Phase II dose finding study for Sansrosa / CD07805/47. Perhaps there is some clue in that Sansrosa is called a gel and V-101 is called a cream, tipping me to guess that this the Sansrosa trial.

Regardless of the topical in question, I would expect that a lab involved in any trial will keep the product and client close to their chests in the interests of keeping blind tests blind.

If anyone is available then please do join the program so that a new treatment for the redness of rosacea can progress closer to possible availability.

This latest trial will compare Sansrosa, or CD07805/47 as Galderma now calls it, in strengths of 0.5% and 0.18% against a placebo containing just the vehicle gel. A total of 260 patients will be studied with an estimated primary completion date of February 2011.

Efficacy and Safety Study of CD07805/47 Topical Gel in Subjects With Facial Erythema Associated With Rosacea

Estimated Enrollment: 260

Study Start Date: August 2010

Estimated Study Completion Date: March 2011

Estimated Primary Completion Date: February 2011

The purpose of this vehicle controlled study is to evaluate the efficacy and safety of CD07805/47 gel 0.5% applied topically once daily (QD) for 4 weeks, and CD07805/47 gel 0.18% applied topically once daily (QD) or twice daily (BID) for 4 weeks, in subjects with moderate to severe facial erythema associated with rosacea.

This trial is in addition to the September 2009 trial covered by Rosacea News as Sansrosa starts Phase II strength tests, still a long way to go. That earlier dose-finding trial compared topical gel concentrations of 0.07%, 0.18% and 0.50% and involved 112 participants.

One could speculate from this just listed trial that Galderma is not impressed with the efficacy of CD07805/47 Gel at 0.07%.

It is well worth noting that Sansrosa is now firmly fixed back in Phase 2 trials, and the all important much larger Phase III trials cannot even be contemplated until at least the middle of 2011.

Since Galderma acquired Collagenex in February 2008, Sansrosa has only headed backwards in its development cycle. Galderma don’t seem to be in any rush to get this product to market. This is surprising as there is such a dearth of treatments for the redness of rosacea.

In June 2008 Collagenex tested topical Sansrosa 0.18% against Bromidine Ophthalmic 0.2% to compare systemic absorption of the active molecule.

Previous Phase 2 dose-finding trials by Collagenex, for COL-118, as they then called it, were made public as far back as August 2007  (see Sanrosa (COL-118) phase 2 looking promising).

Here we are 3 years later, and yet again this product is undergoing trials to determine the percentage of active ingredient that should be further developed.

Whilst it may be easy for those waiting for this product to become discouraged, it is a positive that we at least know that Galderma have the R&D dollars to see this product through. Of course this is itself predicated on Galderma continuing to believe that Sansrosa will become a viable product and make substantive returns for their shareholders.

Sansrosa; the never ending story.

Related Articles

• Sansrosa starts Phase II strength tests, still a long way to go
• Sansrosa ingredients revealed in patent application

Signum Biosciences have announced that their first generation “Signal Transduction Modulator” product, AFC Medirepair (Arazine), is now officially available in Japan.

From the product web site, the product has some other related products names such as Skin Moisture Calm as well as DRx AFC Medirepair. AFC is an abbreviation for the chemical name of Arazine.

AFC Medirepair comes in a 15mL tube and retails for a MSRP 1,890 yen which is around $21 USD. Other snippets from the site suggest that it offers 8 hours of continuous moisturizing. No indication on the site if they are shipping outside of Japan.

The wonderful automatic translation of the Japanese usage instructions is “Dosage taken as a hand, please let me gently soften areas of concern.”

The ingredients listing translates to the following ;

Arazine Ingredients

Water, petrolatum, glycerin, tri (caprylate / caprate), glyceryl, squalane, sorbitan stearate, PEG-40 hydrogenated castor oil, hydrogenated lecithin, Asechirufaruneshirushisutein, TEA, soy sterol, Cetyl alcohol, coconut fatty acid sucrose, xanthan gum, carbomer, peppermint oil, BHT, EDTA-2Na, Methylparaben, Propylparaben

Here is an extract from today’s press release;

Signum Biosciences, Inc. Announces Commercial Launch of Arazine

Proprietary skincare technology platform reaches market

PRINCETON, N.J., July 12, 2010 /PRNewswire via COMTEX/ — Signum Biosciences announced that its partner, Rohto Pharmaceutical Co., Ltd., has launched AFC Medirepair with Signum’s compound Arazine (n-acetyl-s-farnsylcysteine or AFC) in Japan.

Arazine is the first compound from Signum’s novel anti-inflammatory platform to be commercialized from Signum’s pipeline of Signal Transduction Modulators (STMs).

The DRx AFC Medirepair website can be found at: http://www.drx-web.com/aa/prod_afc.htm .

"We’re excited to launch Arazine in the Japanese market providing a completely new and effective product for treating skin inflammation," said Signum president, Maxwell Stock. "The commercialization of Arazine is a significant milestone for Signum and validates our underlying business model."

Arazine is a Signal Transduction Modulator (STM) with anti-inflammatory properties, which has been developed for topical skin treatment.

STMs block inflammation and neutrophil infiltration in chronic redness, acne, skin irritation, and other skin conditions by modulating G-protein signal transduction pathways. They also act as antioxidants to neutralize free radicals and prevent UV damage, cellular degeneration and production of chemicals that cause further damage.

Arazine is closely followed by Signum’s pipeline of compounds including SIG990 which is being developed for rosacea and other inflammatory skin conditions.

Related Articles

• Signum Biosciences developing SIG990 for Rosacea
• SIG990 Excellent for Redness, several years away

Vicept Therapuetics is based in Malvern in Pennsylvania and is a privately held company.

From Fidelity Biosciences Joins $10M Series A for Vicept Therapeutics

“We are delighted by the strong investor interest in this round of financing which will allow us to continue to advance the development of our product pipeline utilizing our novel, patent protected α-adrenergic receptor technology for the treatment of diseases of the skin,” added Dr. Walker. “With this investment, we will have the necessary resources to continue progress with our lead candidate through Phase II for rosacea as well as pursuing other dermatologic conditions including actinic purpura and peri-procedural bruising of the skin.”

Great to see another company getting funding to develop new treatments for rosacea. Obviously there is a belief by venture capitalists that rosacea is a growth market, especially for the treatment for erythema.

The following patent looks likely to be related to the company and their product development.

COMPOSITIONS AND METHODS FOR TREATING PURPURA

(WO/2009/065116)

PCT/US2008/083774

VICEPT THERAPEUTICS, INC

SHANLER, Stuart D; ONDO, Andrew

Embodiments of the present invention are directed to compositions and methods for the treatment of purpura. Preferred compositions comprise an α adrenergic receptor agonist selected from selective α₁ adrenergic receptor agonist, selective α₂ adrenergic receptor agonist, non-selective α₁/α₂adrenergic receptor agonist, agents with α₂ adrenergic receptor agonist activity and combinations thereof, in a pharmaceutically acceptable carrier in order to treat and improve the cosmetic appearance of hemorrhagic (purpuric) lesions in the skin.

The authors of this 2009 patent describe some trials where the following formulations were trialled;

• Oxymetazoline hydrochloride from Afrin Original 12 Hour Nasal Spray
• Naphazoline hydrochloride from Clear Eyes Maximum Redness Relief
• Tetrahydrozoline hydrochloride from Visine Original
• Phenylephrine hydrochloride from Neo-Synephrine Extra Strength Spray
• Brimonidine tartrate from Bausch & Lomb
• Oxymetazoline hydrochloride and brimonidine tartrate combined.

The results of this trial claimed;

… that this demonstrates that selective αi adrenergic receptor agonists and selective α₂ adrenergic receptor agonists, used separately or in combination, when topically applied to and around a treatment site after a procedure that can/will induce purpura, will reduce the size and appearance of the purpuric macules/ patches and is an effective treatment to hasten their resolution.

The source of the purpura in this instance was a pulse dye laser at 585nm.

The publishers of this patent have an additional similar patent that was mentioned by Rosacea News  in 2007;  Sansrosa’s sister to enter redness race

Method and therapeutic/cosmetic topical compositions for the treatment of rosacea and skin erythema using a1-adrenoceptor agonists

United States Patent Application 20050165079

Shanler, Stuart D.; (New York, NY) ; Ondo, Andrew; (Las Cruces, NM)

The present invention is directed to the treatment of skin erythema as exhibited in rosacea and other conditions characterized by increased erythema (redness) of the skin. These conditions exhibit dilation of blood vessels due to a cutaneous vascular hyper-reactivity. In particular, the present invention is directed to a novel composition and method for the treatment of skin erythema using .alpha..sub.1-adrenergic receptor (.alpha..sub.1-adrenoceptor) agonists incorporated into cosmetic, pharmacological or dermatological compositions for topical application to the skin.

Whilst it appears that no new molecules have been discovered, these patents, if allowed, will protect the usage of these formulations to treat the redness of several skin conditions including rosacea. As we have seen with the Sanrosa product it can take many years and a large investment in R&D to progress from a discovery to a sellable product. It is great news that Vicept has secured funding to begin this drug approval process.

Related Articles

• oxymetazoline good for 6 hours and safe for 3 months
• oxymetazoline may be good for 2 years
• AAD Poster Sessions: oxymetazoline
• patents abound for treating rosacea with alpha agonists

Signum Biosciences has several molecules under development, SIG990 is their lead candidate for rosacea.

Anti-Redness Efficacy of SIG0990

In an article perhaps somewhat cryptically titled Signal transduction modulators to treat rosacea, Signum Biosciences introduced us to their work “that targets several stages of the inflammatory cascade, resulting in a significant reduction of redness and erythema. This class of anti-inflammatory STMs inhibits inflammation by reducing the release of critical inflammatory mediators that underlie rosacea pathogenesis, including tumor necrosis factor alpha, interleukins IL-1, IL-6, and IL-8. This leads to a dramatic reduction in neutrophil infiltration and the consequent production of toxic reactive oxygen species.”

(extract) Activity of STMs and topical rosacea treatments.

Using a mouse ear model of inflammation, compounds were tested for activity measuring for the reduction of erythema. Compounds azelaic acid (Finacea 15%), metronidazole (Metrogel 1%), brimonidine 0.2%, STMs (SIG0990 4%).

The above graph extracted from the article published in the RRDi journal is a teaser for more detailed data that has been presented at the Society of Investigative Dermatology 2010 Annual Meeting in Atlanta, Georgia. More on that paper soon.

The graph suggests that in their studies, SIG990 potentially has superior anti-erythema effects compared to both the well known Finacea and Metrogel products and the yet-to-be-approved Brimodine based (Sansrosa) product.

Good News for Rosacea Sufferers

If this research translates safely and effectively to human skin then Signum Biosciences’s data suggests that they may have a new class of anti-erythema product on its hands.

As we know from the development pipeline of other developing treatments, the path from interesting molecule to approved product is measured in years and fraught with delays and pitfalls. Dr. Pérez estimation of this product being several years away seems to be a fair estimate to heed.

Arazine Available Soon

Dr. Pérez has confirmed that their first-generation-molecule based product known as Arazine will available next month (June 2010) via Rohto Pharmaceuticals in Japan.

[update]: DRx AFC Medirepair (Arazine) is now available in Japan.

Related Articles

• Signum Biosciences developing SIG990 for Rosacea
• How to cure a red face

The aim of this trial is show which strength is the most suitable for general use. Trial participants will be using one of 4 different strengths: 0.07%, 0.18%, %0.50 or effectively %0 contained in the gel vehicle. This trial should be completed by the end of the year, paving the way for an eagerly anticipated FDA approval in 2010.

Rosacea News previously found a patent application listing the full ingredients for Sansrosa, which included a mention of the active ingredient Brimonidine tartrate at a concentration of 0.18%. This trial suggests that Galderma is now also interested in a almost 3 times as strong version of %0.50.

The trial details again confirm that Sansrosa is to be applied once per day and that benefits can be expected for up to 12 hours after application. The patent related to the Sanrosa product itself suggested that typical usage was 1-4 times per day.

Galderma is looking for 112 participants, and the register suggests that residents of Pennsylvania, Texas, Virginia  and Arkansas are eligible. Please do post below if you get to be a part of this final phase of testing.

Galderma acquired the Sansrosa product through their acquisition of Collagenex. Rosacea News has been following this product for several years now, since Collagenex first started talking about a new product COL-118, in 2006.

Galderma is now back at one of the Phase II tests for a new drug. This seems disappointing given that Phase 2 Trials were thought to completed in August 2007 and Phase III was slated to commence in early 2008. One can only speculate that Galderma wasn’t satisfied with the progress and likely success of sansrosa and has sent it back for further testing.

It has been a long slow process, but it is encouraging to see that Galderma is still investing in developing this much-awaited product.

Read more of my extensive coverage of Sansrosa News.

Dose-Finding Study of CD07805/47 Topical Gel in Subjects With Erythematotelangiectatic Rosacea

This is a randomized, double-blind, parallel-group, vehicle-controlled, dose-finding study to investigate the pharmacodynamics and the safety of three dosages of CD07805/47 topical gel (0.07%, 0.18%, and 0.50%), after a single application in subjects with a clinical diagnosis of stable moderate to severe erythematotelangiectatic rosacea. Subjects will be randomized in a 1:1:1:1 ratio to receive either one of three CD07805/47 topical gel concentrations (0.07%, 0.18%, or 0.50%) or Vehicle Gel. All subjects will be treated with a single application (once daily dosing for one day) of study medication.

Update: the Dose-Finding has now completed. Note that these trials are part of the Phase II of development of sansrosa. Before a new drug can be approved by the FDA, Galderma must  conclude well-controlled Phase III trials and/or Long Term safety studies.

Related Articles

• Sansrosa ingredients
• DermatologyTimes: Sansrosa not available for several years
• Sansrosa Phase 3 Delayed until END of 2008
• COL-118/Sansrosa $150+ a month ?

The article mentions the positive results from the “most recent research” on Brimonidine ;

In the most recent research, a double-blind study for Galderma, a 1 g application of 0.18 percent COL-118 facial gel (1.8 mg brimonidine) was administered topically in the morning; a second, four hours later. The erythema began decreasing within an hour, and the results lasted most of the day.

Almost suggesting that the real success of Sansrosa is it’s placebo effect are the following comments ;

Dr. Leyden describes the redness as significantly reduced when the brimonidine is applied, and he says that patients are thrilled with the results.

"They’re ecstatic. They know the result isn’t permanent and will wear off in a matter of hours, but just the fact that redness can be controlled is more than what they have had," Dr. Leyden tells Dermatology Times.

While there is no medical reason for the preparation to have a lasting effect on a patient’s basic rosacea erythema, Dr. Leyden says some improvement can often be seen in that baseline redness.

"It may be because stress is one of the contributing factors in rosacea. Once the patient knows there is a way to reduce the redness, they worry less about a flare-up, and the base redness decreases as a result," he says.

Whilst is it fine to state that the method of operation is unknown, claiming a drug’s success is psychological is a little concerning. Whilst the placebo effect is well known and somewhat understood, it naturally doesn’t form any solid basis for a product’s success. One has to ask whether the product will be universally successful across the population if an important part of the treatment is the belief that it will work. Having said all this, it might just be a throw away line, as indeed double-blind placebo-controlled trials are designed to prove that the active agent is effective.

Moving on to discuss Oxymetazoline, the article quotes Dr. Shanlen and covers information that is well known to readers of Rosacea News (oxymetazoline may be good for 2 years).

Dr. Baumann cautions about the topical use of Afrin;

"I would caution patients with rosacea not to go out and apply straight Afrin on their skin. Afrin contains several ingredients that can be irritating. But the ingredients used in Afrin do show signs of offering a breakthrough in rosacea treatment in the future," she says.

We also know from the Feb. 2008 meeting of the AAD that oxymetazoline is effective for up to 6 hours after application, and that no negative side effects have been seen after 3 months usage.

Dr. Shanlen holds a patent on the usage of oxymetazoline to treat rosacea.

This DermatologyTimes article is in addition to some encouraging publicity at the recent AAD Meeting in SFO, which also highlighted Oxymetazoline as a treatment for rosacea.

Related Articles

• oxymetazoline may be good for 2 years
• AAD: oxymetazoline, dapsone and light therapy
• Sansrosa’s sister to enter redness race
• Sansrosa has neuro protective properties
• Sansrosa composition revealed in patent application

Those following the development of sansrosa closely will be encouraged by this patent application; making this new treatment seem one step closer to being available.

Brimonidine Compositions for Treating Erythema, United States Patent Application 20090061020

The present invention is directed to a pharmaceutical composition including brimonidine tartrate in an amount from about 0.17 percent by weight to about 0.19 percent by weight in a pharmaceutically acceptable carrier such as a gel or cream. The invention also relates to a method of treating erythema in a patient with rosacea by administering the composition of the invention to the site of erythema on the skin of the patient.

More extracts:

A composition wherein the gel comprises water, a gelling agent, a skin-penetrating agent (propylene glycol), a moisturizer (glycerin), a preservative (methylparaben or phenoxyethanol), a gelling agent (Carbomer 934P), a protective agent (titanium dioxide), a carrier to have a pH of about 5 to about 7.5 (sodium or potassium hydroxide)

A composition wherein the gel comprises water, a carbomer, propylene glycol, glycerin, methylparaben, phenoxyethanol, glycerin, titanium dioxide and a sufficient amount of base to cause the carrier to have a minimum pH of about 6.2 and a maximum pH of about 6.8 when the gel is diluted by a factor of ten.

Later on we can see the relative amounts of each component.

Gel Formulation

The Phase 2 studies used a composition similar to the above gel formulation. Three strengths were used for the trials – 0.02%, 0.07% and 0.20% brimonidine tartrate. The placebo of course contained no brimonidine tartrate. A strong benefit in reduction of erythema was seen in the mid and high doses.

Cream Formulation

Dosage

We can also see that `Typically, one to four applications per day are recommended during the term of treatment.’

Do you see anything you don’t like ? Anything interesting or of concern given your own experience with topicals ?

Related Articles

• Sansrosa has neuro protective properties
• Sansrosa gel vs. eyes drops absorption trial details posted
• COL-118/Sansrosa $150+ a month ?

We know from patent filings that the active ingredient in the in-development sansrosa product is brimonidine tartrate. This is also the active ingredient in Alphagan P, a treatment for glaucoma.

Alphagan P 0.1%, is known as an alpha2-adrenergic receptor agonist, and is used to lower intraocular pressure and reduce ocular hypertension. Around 10-20% of users of Alphagan P experience adverse side effects including conjunctivitis, swelling of the conjuctiva and itchiness of the eye. Extreme caution is advised in patients with cardiovascular disease.

Sansrosa, also known by its in-house name COL-118, is based on brimonidine tartrate, and is in the process of being assessed by the FDA and it believed to be scheduled to start Phase 3 trials in early 2009.

A recently published paper has shed some light on the method of operation of brimonidine tartrate. This could be interesting to rosacea sufferers, especially those investigating the link between nerve mediated flushing and rosacea. Could the active ingredient also help rosacea sufferers by protecting against nerve damage in your skin ? This is a question that I think is worth investigating.

After topical instillation, brimonidine reduces intraocular pressure within 1 hour, and the peak effect occurs at 2–3 hours after dosing. Preclinical trials have shown that brimonidine has neuroprotective effects in animal models of optic nerve damage. Neuroprotection has been investigated as a therapeutic approach for neurodegenerative conditions including stroke, spinal cord injury, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Alzheimer’s disease.

Interestingly, systemic administration of brimonidine, which does not reduce Intraocular Pressure, is also neuroprotective.

Clinical efficacy and neuroprotective effects of brimonidine in the management of glaucoma and ocular hypertension

Abstract: Elevated intraocular pressure (IOP) is a signifi cant risk factor for the development and progression of glaucomatous optic neuropathy, but increasingly we appreciate that non-pressure dependent factors, are key to our understanding of the pathophysiology of these neurodegenerative diseases, that target the retinal ganglion cell. As we try to expand therapy beyond IOP control, medications are being assessed for their neuroprotective abilities. Brimonidine is an effective ocular hypotensive treatment both as a fi rst and second line agent, in the management of glaucoma and ocular hypertension. Brimonidine tartrate 0.2% is generally safe and well tolerated, with its safety profi le further enhanced in the altered formulation brimonidine-Purite™ 0.1%. Beyond brimonidine’s pressure lowering capacity, laboratory and early clinical evidence supports its neuroprotective potential. We await validation of this in human clinical trials. 

Keywords: brimonidine, neuroprotection, clinical effectiveness, tolerability

Related Articles

• Collagenex CEO says rebound not yet seen in Sansrosa
• Sansrosa’s sister to enter redness race
• DermatologyTimes: Sansrosa not available for several years
• Sansrosa Phase 3 Delayed until END of 2008
• Sansrosa composition revealed in patent application

One article talks about how Galderma/Collagenex is excited about new possible drugs. It doesn’t directly name the Sansrosa product, but it does have a little note that it `likely won’t be available for several years’. If that is a direct quote from Dr. Schlessinger, a long term investigator from Galderma/Collagenex then that will be discouraging news for many.

Now on trial: New rosacea medications hold promise for future

One of the medications being studied by scientists at Galderma Laboratories acts as a vasoconstrictor. A topical gel, it decreases redness around the area for up to 12 hours, a considerable increase over current treatments. The compound has shown very dramatic results and is beneficial for people with significant rosacea, according to Dr. Schlessinger.

Although initial trials have been conducted, the product likely will not be available for several years.

Collagenex had an excellent Public Relations engine and were normally very quick to release any official news about upcoming products – especially one would imagine if that might effect investors’ view of the company. Since Galderma purchased Collagenex, the Collagenex web site has morphed into a Galderma corporate site, and subsequently lost a lot of the bleeding edge information about Sansrosa. This would be as expected, now that the much smaller operations of Collagenex, and indeed SansRosa Pharmaceutical Development have been merged into Galderma.

The latest official information from Galderma was that they `anticipate completing the study in the third quarter of 2008 and commencing our Phase III clinical trials before the end of 2008’ (Sansrosa Phase 3 Delayed until END of 2008).

We know that in May 2008 details of the commencement of the additional Phase 2 trials were posted on clinicaltrials.gov, and shortly later the trial was listed as completed. Apart from that, we are still waiting for more official news. While we wait, we are left wondering if the Phase 2 trials didn’t go well, or if it is just the  wheels of bigpharma drug development processes turning slowly.

Related Articles

• Read more of the comprehensive coverage of Sansrosa News
• Collagenex CEO says rebound not yet seen in Sansrosa
• COL-118/Sansrosa $150+ a month ?
• Sansrosa’s sister to enter redness race
• oxymetazoline good for 6 hours and safe for 3 months