Study of 0444 Gel in the Treatment of Inflammatory Lesions of Rosacea

Sponsor: Nycomed US Inc

The aim of this trial is to assess the efficacy of 0444 Gel in the Treatment of Inflammatory Lesions of Rosacea.

Treatment medication will be administered as follows: A thin film of gel will be applied and rubbed into the entire face once daily for a period of 70 days.

So what could this gel be ? As far as I can see, likely candidates include Solaraze as well as a new generic form of metrogel. These two classes of products are manufactured by companies related to or owned by Nycomed.

Solaraze

We learnt from a 2006 AAD Poster Session that Solaraze was being studied as a treatment for rosacea. SOLARAZE (diclofenac sodium-3%) Gel is indicated for the topical treatment of actinic keratoses (AKs).

SOLARAZE Gel is a registered trademarks of PharmaDerm, a Division of Nycomed US, Inc.

Solaraze is currently marketed in the US, Europe and Australia.

Generic Metrogel

Nycomed has a sister division Fougera Generics. A press release in 2005 alterted us to the fact that Fougera was poised to make generic metrogel 0.75%. Indeed you can find details on Fougera’s web site for Metronidazole Topical Lotion 0.75% (compares to MetroLotion) and Metronidazole Topical Cream 0.75% (compares to MetroCream).

Other Guesses

Any other guesses ? If you have more information about 0444 Gel please post in the comments below.

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I was alerted to the launch of a product called Promiseb by a comment left on the Sebclair for Seborrheic Dermatitis post. Since then the news web sites are also covering the press release. Promiseb (probably pronounced Promi-seb) is launching in the U.S. via Promius Pharma, after being licensed from Sinclair Pharma in 2007.

Promiseb Topical Cream (Sebclair) is a non-steroidal, prescription only cream for the treatment of seborrheic dermatitis. It has demonstrated anti-inflammatory and anti-fungal properties. Sebclair is approved for use in the European Union to treat seborrheic dermatitis. One of Sebclair’s (and now Promiseb’s) claims to fame is that it contains no corticosteroids or immunomodulating agents.

Promiseb is claimed to “Significantly reduced Malassezia yeasts, the organisms that may cause seborrheic dermatitis, by 94%”. These claims are more interesting when you consider the ongoing discussions like Malassezia Globosa causes seborrhea, Pyrithione Zinc is effective, Could M. Globosa Cause Rosacea? and Real cause of seborrhea discovered!.

For a description of the ingredients and suggested method of action see Sebclair for seborrheic dermatitis.

From the press release: Sebclair launched in the US by Dr Reddy’s Laboratories’  subsidiary Promius Pharma, LLC

Jeff Wasserstein, President of Promius Pharma, said “We are very excited about Promiseb Cream because it has the potential to replace both anti-inflammatoryand antifungal treatments in patients with seborrheic dermatitis. In a clinicalstudy Promiseb was shown to have efficacy comparable to desonide cream 0.05% atdays 14 and 28 with fewer relapses.

“Promiseb Cream also has an excellent safety profile with no restrictions onage, duration of use or application on the face.” He continued, “We are very enthusiastic about this product because our clinical research shows thatPromiseb Cream may be used as a first-line treatment for seborrheic flares andfor long-term maintenance”

A supporting web site for Promiseb is online at http://promiseb.com/.

[update:] Auburn-NH has posted an early review of Promiseb, from using a doctor supplied sample.

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This post-treatment therapy is in addition to some other recently published research that patients treated immediately after IPL with a LED device showed that their post-treatment redness subsided faster compared to not also being treated with LED.

We also know that 2% polyphenone in a hydrophilic cream has shown promise as a treatment for the papules and pustules of rosacea.

Topical polyphenolic antioxidants reduce the adverse effects of intense pulsed light therapy, J Cosmet Laser Ther. 2009 May 27:1-4, Freedman BM., Plastic Surgery Associates of Northern Virginia, McLean, Virginia, USA.

Background: Intense pulsed light therapy (IPL) has been associated with erythema and increased lipid peroxidation. Polyphenolic antioxidants have been shown to decrease inflammation and reduce oxidative stress in irradiated skin.

Objective: To determine whether the topical application of polyphenolic antioxidants to IPL-treated skin reduced the adverse effects of IPL exposure.

Methods: In a split-face study, 10 volunteers underwent three full-face IPL treatments (16 J/cm(2), 10ms, 560nm filter) spaced 3 weeks apart. A polyphenolic antioxidant solution was pneumatically applied to the left side of the face, beginning immediately before the first IPL treatment then weekly for six treatments. The lipid peroxide concentration, skin antioxidant level and skin moisture content were obtained before and after the study.

Results: Skin treated with IPL alone contained a significantly higher concentration of lipid peroxides when compared to skin treated with IPL plus polyphenolic antioxidants (p<0.05). Skin treated with IPL alone contained a significantly lower level of polyphenolic antioxidants and had a significantly lower moisture content (p<0.05).

Conclusions: In this study, the concurrent pneumatic topical application of polyphenolic antioxidants reduced lipid peroxidation and skin dehydration in IPL-treated skin. Polyphenolic antioxidants may confer a protective effect on facial skin and enhance the effects of IPL therapy.

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Showing just how important the internet is becoming for marketing new cosmetics, Pyratine XR has recently launched with a lot of press activity. As well as Senetek’s press releases on the internet I was also contacted by 2 PR representatives trying to get me to cover the release of this `new’ product. Pyratine XR was launched at the South Beach Dermatology Symposium in Miami on Feb 14 and also on March 6 at the AAD Annual Meeting in San Francisco.

The press release activity is based on an as-yet unpublished study of 18 mild to moderate rosacea over a period of 48 weeks.

So what is the difference between Kinerase, Pyratine-6 and Pyratine XR ? Well firstly they are all expensive over the counter cosmetics. The active ingredient in these products is furfuryl tetrahydropyranyladenine. As cosmetic products none of these can make claims to treat any particular disease.

Kinerase

Kinerase Cream contains 0.1% N6-furfuryladenine.

The ingredients of Kinerase are listed as: purified water, glyceryl stearate and laureth-23, isopropyl palmitate, propylene glycol, stearic acid, cetyl alcohol, carthamus tinctorius (safflower) seed oil, soya sterol, stearyl alcohol, dimethicone, imidazolidinyl urea, citric acid, sodium hydroxide, methylparaben, soluble collagen, carbomer, N6-furfuryladenine, panthenol, propylparaben, triethanolamine, ascorbic acid, hydrolyzed elastin, and aloe barbadensis leaf juice.

Pyratine-6

Pyratine 6 contains 0.1% N6-furfuryladenine and is marketed as an anti-aging product and as Senetek’s `second-generation patented cytokinin’

Pyratine XR

Pyratine XR contains 0.125% N6-furfuryladenine and is marketed as a rosacea product once Senetek increased the amount of the active ingredient and initiated the unpublished study mentioned in this article. It looks to me that the Red R in the labelling is also trying to suggest that this product is for rosacea sufferers.

Product Feedback

There is some strong skepticism about Pyratine XR over at the Rosacea Forum

I agree with Melissa:

1. The stuff is ridiculously expensive
2. It went "cosmetic" as to avoid having to conduct rigorous testing
3. It’s claims are yet to be approved by the FDA as far as I could find
4. There are no 3rd party tests of this product, only in house research done by the company
5. In the tests that were done the claim was that it was tested on people with mild to moderate rosacea, but the test data itself remains largely unpublished.
   Further: http://www.dermatology.uci.edu/IID%2…er%20final.pdf
   Are you kidding me? If the two test subjects pictured are the best examples to sell this product then it appears to only work well for those with really, really, really mild Rosacea.
6. I haven’t heard one good thing about Pyratine 6 from a real Rosacea sufferer, it is hard to imagine why this is going to be that much better
7. Spamming Rosacea web boards for business suggests a $ grab
8. I don’t know why this plant derivative substance is significantly different from others that have been around for some time that claim to also be anti-inflammatory and effective on ROS.
   Bottom line, there is no real reason to believe this product will work imo, but the jury is out. Once is comes out, if some reliable people post good results it might be worth a try. I would prefer seeing a large scale 3rd party double blind study on it.

Pyratine XR was due to be launched at the SF AAD Meeting. An interesting post from badhairday gives some insight into what this launch actually meant ;

Hi all,

Thought this would be helpful info re: Pyratine XR. I realize I don’t regularly post but I thought this was important. My sister in-law is a Derm. She attended the National Dermatology Conference in San Francisco this past weekend. I asked her to find this product and try to get me the inside scoop – like all of us I am cautiously hopeful of anything new but also skeptical. Here’s what she found.

The Pyratine XR booth – was a VERY hard to find tiny booth. There were two women representing the product (she said the ladies seemed a little sketchy – not necessarily important info but I trust my sisters judgement ). Just a few before and after pictures of people who had trialed it for 48 weeks – but NO real data on how the product works and the women wouldn’t get into any detail. They would only conditionally commit to give her 6 free samples (enough for the 48 months per patient) BUT the Dr. had to commit to recording results of their patients (data and pictures) through the period of the trial and report back to the company. If the Dr. didn’t want to commit to the following though on data gathering they would need to pay $400 + per patient (for an 48 month trial). This product will be sold over the counter only in physician offices (no pharmacies). My sister-in-law was concerned that this company was trying to solicit Doctors to do the research for them for free rather than setting up an actual study where patients are paid. Further she was sceptical that they wouldn’t give any free samples (it is $150 per tube!)

She reported that b/c it’s over the counter it doesn’t have to go though any "real" testing (a lot easier to get approved). Just need to prove that it doesn’t harm anyone. It seems to be a glorified anti aging product with natural plant exact ingredients which probably will be ok for many of us to use as most of the ingredients looked fairly benign. But it’s hard to say if it will have any effect on rosacea at this point. Her recommendation was to wait a year and not spend the money as it didn’t look promising enough and it didn’t have enough to back it up that would make it a worth while product at this point. Sorry to burst any bubbles – and again what doesn’t work for one may work for another and obviously a few people on this sight have had some luck. The product representation just seemed a little sketchy for me.

Good luck all – hope this helps a few of us to save a few bucks and… Jen

Paula Begoun has this to say about Kinetin.

Kinetin is a plant-growth hormone, and its technical name is N6-furfuryladenine. What makes kinetin interesting are the in vitro and animal studies demonstrating its effect as a growth factor.

…

I suspect that when it’s applied topically, kinetin isn’t of much use to the skin cell, and even if it could be utilized, there probably isn’t enough kinetin in any product to have a negative or positive impact but that is only a guess, no one knows for sure (Source: Dermatologic Clinics, October 2000, pages 609-615).

User Reviews & Feedback

As Pyratine XR has only recently launched there aren’t many testimonials available yet. Here are some thoughts from users of the related product Pyratine 6.

From DukeCity; I still am using the creme and think it’s the best moisturizer I’ve ever had, as far as toning down redness it’s so subjective, as I’ve had multiple IPL/Laser TX and am taking Oracea daily. But it is the only topical I’ve been using since last Feb./March. I will definitly be buying the Pyratine/RX as soon as it comes to public sale…

From dallascowgirl; On March 14, 2009, I will have completed a year using Pyratine- 6 lotion. (I tried the cream but it made my skin break out.) I still like it as much as ever– the first moisterizer I’ve ever been able to use. In this year, I have only used two 2.5 oz. tubes. I use a pea size glop twice a day while my face is slightly damp. I have had acne rosacea since I was 13 years old. Today, I have no breakout and my face skin is smooth, a little pink on my chin. Though it is expensive, I think I’ve actually saved money this year from not running out and buying the newest cream every month. Will I try the the new one? I really haven’t decided yet.

From sophie; I started using Pyratine last sept or oct, and loved my skin more after only a week or two. There has been a SMALL reduction in P&Ps [I still have them]. Likewise a SMALL reduction in redness [I'm still red]. The BIG difference was in the overall smoothness of my skin. Its still rougher than your average persons, but I’m quite sure that its the smoothest its been since pre-puberty [I'm now 33]. Funnily enough, I wonder whether my spider veins are now more defined now cause my skin is clearer. The other downside is that prolonged use hasn’t made my skin any better i.e. the almost immediate improvement has remained but not increased.

Over to You

So now that you have read all this background information, do you plan on trying Pyratine XR ?

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So now you know; you can apply your topicals before or after you moisturize and it won’t make any difference.

Impact of order of application of moisturizers on percutaneous absorption kinetics: evaluation of sequential application of moisturizer lotions and azelaic acid gel 15% using a human skin model, Cutis. 2009 Mar; 83(3):119-24., Del Rosso JQ, Lehman PA, Raney SG., Valley Hospital Medical Center, Las Vegas, Nevada, USA.

The medical management of rosacea increasingly has involved not only the appropriate selection of topical medication but also patient education and specific recommendations regarding appropriate skin care. The recognition that epidermal barrier dysfunction and transepidermal water loss (TEWL) play a pathophysiologic role in rosacea and that skin moisturization may help to mitigate signs and symptoms of the disease has led to a deeper appreciation of the importance of proper skin care in the treatment of rosacea. Data from a percutaneous penetration study performed using human skin suggest that any of the tested moisturizer lotions may be applied either before or after azelaic acid gel 15% without a major change in the percutaneous absorption profile of azelaic acid.

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Continuing recent consolidations in the pharmaceutical industry is the report that the giant GlaxoSmithKline (or GSK) are to purchase Stiefel. Stiefel is the manufacturer of Rosac Wash and Rosac cream with Sunscreens. Stiefel is also the makers of Rosasol – a formulation of metronidazole with SPF15 available in Canada.

Stiefel is also a supporter of the National Rosacea Society, having offered unrestricted educational grants in the past.

Rosac is a topical preparation that combines 2 sunscreens with sodium sulfacetamide and sulfur.

GSK is not known for its rosacea products, perhaps the closest they have ventured so far is Spectro Jel.

WSJ: GlaxoSmithKline May Buy Stiefel for $3B

GlaxoSmithKline (GSK: 30.61, -0.25, -0.81%) is close to a deal to acquire Stiefel Laboratories for around $3 billion, The Wall Street Journal reported, citing people familiar with the matter.

Major pharmaceutical industry players are rushing to merge to beat back growing competition from generic drug makers and replenish their product pipelines. So far this year a number of deals have been announced, such as Pfizer’s (PFE: 14.18, 0.29, 2.09%) pending buyout of Wyeth (WYE: 43.24, 0.37, 0.86%) and Merck’s (MRK: 25.7963, -0.0537, -0.21%) pending takeover of Schering-Plough (SGP: 23.4, 0.13, 0.56%).

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ADMINISTRATION OF TROPISETRON FOR TREATING INFLAMMATORY SKIN DISEASES/DISORDERS, United States Patent Application 20090048289.

Tropisetron or salt thereof, formulated into diverse pharmaceutical/dermatological compositions, is useful for the treatment of a variety of inflammatory skin disorders/diseases, e.g., eczema, psoriasis, rosacea, acne vulgaris, ulcers, seborrhoeic dermatitis and irritations induced by chemical, physical or mechanical agents, notably rosacea.

Tropisetron has been approved in the past in palliative therapy to prevent or treat chemotherapy induced nausea and vomiting and to treat post-operative nausea and vomiting. Tropisetron is not available in the United States.

Tropisetron has been found effective in treating rheumatic arthritis, IBS, diarrhoea, central nervous system related disorders like anxiety, drug addiction, cognitive functions, myofascial pain, chronic fatigue syndrome, fibromyalgia and certain forms of pruritus.

Further, Claim 8 in the patent application is interesting;  “there is, however, no published data regarding the use of tropisetron in order to treat an inflammatory skin disorder/disease and preferably rosacea”. If indeed Galderma have found this agent to be effective in treating rosacea, they may well end up owning the patent outright.

The claims proposed in the patent embody a topical agent being a gel, cream or lotion with a concentration from 0.0001% to 20%. The claims also mention topical application to the eye and cover oral and sub cutaneous preparations as well.

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EXCITING NEWS

We have just received word that four products that have been important to many rosacea sufferers will be available again later this spring. By arrangement with the originator of these products, the Rosacea Care Company will be manufacturing and distributing ZincO, Tinted ZincO, Vita-Oil and Oatmeal Cleanser.

The formulas will be exactly the same as the originals, and they will be manufactured by the same laboratory. They will appear as part of the Rosacea Care catalogue with a slight increase in prices. These much loved products will be available on-line at rosaceacare.com.

I have been asked to tell you that the exact release dates have not yet been established. Please don’t contact Rosacea Care at this time. As soon as availability dates are known, they will be posted here and on their web site. Thanks to all of you who participated in our recent poll which provided valuable information and encouragement to those involved.

Disclaimer: Rosacea Care is a site sponsor of rosacea-support.org 

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It appears to be called Atopiclair and is available from
http://www.atopiclair.com.au/ It is listed as Atopiclair Cream 40ml and is $49 including postage to anywhere in Australia.

The web site claims a “new, non-steroidal cream that is designed to relieve the symptoms and signs of eczema (atopic dermatitis) and allergic dermatitis (contact dermatitis).”

Going by the papers they cite on that page and the paper above both quoting MAS063DP (Atopiclair[TM]), and the fact that Otco Global is listed as the Australian distributor – I’d say that this is Sebclair.

Sebclair (MAS064D) is approved for use in the European Union to treat seborrheic dermatitis. One of Sebclair’s claim to fame is that it contains no corticosteroids or immunomodulating agents. The paper’s authors admit that it is difficult to know which compound is responsible for Sebclair’s success as a treatment.

The authors state “We believe that the major activity is probably due to the synergistic effect of both piroctone olamine, for its antimycotic action, and glycyrrhetinic acid, for its anti-inflammatory action.”

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The mechanism of action of calcitrol in the treatment of psoriasis has not been established but Vitamin D3 has been shown to contribute "to the regulation of development and function of mast cells, which play a critical role in several inflammatory disorders”. Also it seems to have important immunomodulating effects, both reducing levels of pro-inflammatory cytokines and increasing levels of anti-inflammatory cytokines. See RSRP: Vitamin D3 for more information.

The Vectical prescribing information says that it should not be applied to the eyes, lips or facial skin. This may well limit the applicability of Vectical to treat rosacea of course. With all of the interest in Vitamin D3, this new product does look interesting though.

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