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.

Related Articles

• Solaraze (diclofenac sodium topical gel) being studied
• metronidazole (metrogel, flagyl) popular rosacea treatment
• generic metrogel soon – Fougera

A summary from a the recent 18th Congress of the European Academy of Dermatology and Venereology has presented some findings relating to the most effect dosage of accutane to treat rosacea.

Accutane (Isotretinoin) has been successfully prescribed in low doses to treat rosacea, and especially the `lumps and bumps’ of rosacea that have not responded to other treatments.

Despite some good published papers that deal with treating rosacea with low doses of accutane, officially isotretinoin needs to be prescribed `off label’ for treating rosacea.

For those enrolled in this blind study, 0.3 mg/kg per day was found to be as effective as 50mg a day of doxycycline at treating the papules, pustules and phymatous growth of rosacea.

Getting the dose right is important if you want to try Isotretinoin as a treatment for your troublesome rosacea. How do you know if you are taking too much ? A high dose of accutane can lead to unpleasant side effects and even worsen the flushing associated with rosacea.

If you consider an average weight of 166 pounds (around 75kg) this paper would lead to a recommended dosage of around 22mg a day. Even this amount may be viewed as moderate to high when compared to advice from Dr. Plewig that “doses of isotretinoin typically used in the United States and Europe are far too high. For many patients, as little as 2.5 mg twice a week, which he describes as `a drop of rain on a dusty road’ is adequate.”

Dr. Erdogan et.al. suggested that “In our small group, using a daily dose of 10 mg of isotretinoin, we did not observe such adverse effects. Although we selected patients resistant to treatment with a long history of complaints, our results confirmed the efficacy of isotretinoin use, but whether remissions will continue after the cessation of treatment is not addressed by our study.”

Further, advice from Dr. Hofer suggests doses of around 3mg to 8mg in what he calls his continuous microdose regime are suitable for treating rosacea. In 2000, Palmer et al. showed that continuous microdose isotretinoin (CMI) treatment (0.04-0.11 mg/kg daily) was sufficient to control adult relapsing acne, but they mentioned that this is an unlicensed method administration.

This paper will hopefully give some weight to the argument that under controlled circumstances, in the right doses, and for the indicated rosacea symptoms, low dose accutane can be a viable treatment.

If indeed this research helps lead to accutane being available as an on-label prescription for rosacea sufferers, then that is good news especially for those desperate for relief from the recalcitrant lumps and bumps of rosacea.

Optimal Isotretinoin Dosing for Rosacea Identified

BERLIN (EGMN)–Isotretinoin could be headed for a new indication as a licensed treatment for rosacea.

The workhorse oral retinoid has been used off label to treat challenging cases of rosacea for more than 2 decades. However, Barcelona-based Almirall recently sponsored a successful multicenter randomized trial aimed at earning an indication from regulatory authorities for its branded version of isotretinoin in the treatment of rosacea, Dr. Harald Gollnick said at the annual congress of the European Academy of Dermatology and Venereology.

The double-blind, 12-week study involved 224 patients with the papulopustular or phymatous forms of rosacea. Participants in the five-armed trial were randomized to isotretinoin at 0.1, 0.3, or 0.5 mg/kg per day; doxycycline at 100 mg per day followed by 50 mg per day; or placebo, explained Dr. Gollnick, professor of dermatology at Otto-von-Guericke University, Magdeburg, Germany, and president of the European Board of Dermato-Venereology.

The optimal isotretinoin dose proved to be 0.3 mg/kg per day. Its efficacy was superior to placebo and similar to that of doxycycline, with both regimens achieving a 90% reduction in papules and pustules at 12 weeks, according to Dr. Gollnick, who is also chairman of the Global Alliance to Improve Outcomes in Acne, an international group of acne experts.

“That means in the near future we’ll most probably have an on-label indication for isotretinoin in rosacea,” he said.

Over the years isotretinoin has been used off label to treat rosacea, but the best dose was a matter of guesswork. The Almirall-sponsored trial is particularly welcome because it is the first formal study aimed at defining the optimal dose, added Dr. Gollnick.

The 0.3 mg/kg dose was associated with a low rate of side effects, consisting mainly of mild lipid changes and liver enzyme elevations. The 0.5 mg/kg dose wasn’t any more effective, and it produced more irritation and facial dermatitis. The 0.1 mg/kg dose, while significantly better than placebo, was less effective than 0.3 mg/kg.

Topical therapies for rosacea include 0.5%-2% metronidazole, azelaic acid, 0.025% tretinoin, and 2.5%-5% permethrin. Systemic treatments include metronidazole at 500 mg/day, minocycline at 50 mg/day, tetracyclines at 0.5-1.5 g/day, and a subantimicrobial formulation of doxycycline.

Over to You

What dose of accutane have you found to work best for you ?

Related Articles

• low dose doxycycline hyclate (SDD)
• Subantimicrobial Dose Doxycycline for Acne and Rosacea
• focus on low-dose accutane
• long term extra low dose accutane

A previous study in 1994 also found that Vitamin K cream reduced the severity of post PDL purpura.

Whilst the redness and indeed purpleness that Pulsed Dye Laser treatments can cause will heal without intervention, any option to reduce the downtime after treatment will be welcomed.

Pulsed Dye Laser treatments can also be extremely painful. A 2009 paper detailed the use of Pnuematic Skin Flattening to reduce the pain of PDL.

Topical formulations of Vitamin K Oxide are currently available via some doctors and indeed online. A product range from Biopelle known as Auriderm suggests the following to support the promotion of its’ products; “It’s the Vitamin K Oxide – not the Vitamin K – that clears unwanted discoloration and builds vasculature. Vitamin K was effective because it provided the raw material to create Vitamin K Oxide, which really did the work.”

The science of Vitamin K Oxide

Vitamin K has shown effectiveness in dealing with this because it initiates the Vitamin K cycle of healing: In the event of trauma, Vitamin K converts to Vitamin K Oxide, activating the Coagulation Factors in the clotting cascade. The cycle continues when Vitamin K Oxide converts back to Vitamin K, converting the staining ion (Fe+3) to the more easily absorbed ion (Fe+2), blocking and/or reversing the formation of hemosiderin.

Vitamin K itself is inherently unstable in topical formulations, perhaps explaining why Vitamin K topicals so far haven’t to date shown huge promise as rosacea treatments.

It is also worth noting that is has been shown that some people are allergic to Vitamin K. Also note that Auriderm suggests that Arnica Montana tablets be taken post-operatively, but some caution may be advised – Paula Begoun, in her article, When Blushing is Not by Choice: Causes and Treatments for Rosacea (web archive link), lists Arnica as something that potentially should be avoided.

Finally a related word of warning from a 2007 Scientific Committee on Consumer Products opinion on Vitamin K1 (phytonadione) suggested that;

Because of the inadequate nature of the dossier submitted, the SCCP is unable to provide an adequate safety evaluation for the use of vitamin K1 (phytonadione) and its "oxide" in cosmetic products. However, as such use may cause cutaneous allergy, individuals so affected may be denied an important therapeutic agent.

Now to the Abstract:

The role of topical vitamin K oxide gel in the resolution of postprocedural purpura.

J Drugs Dermatol. 2009 Nov;8(11):1020-4.

BACKGROUND AND OBJECTIVE: Facial purpura is a frequent barrier to patient acceptance and satisfaction with the results of various cosmetic procedures. Methods to shorten the duration of purpura after such procedures are often sought by patients. This study evaluated the efficacy and safety of a topical gel containing vitamin K oxide in the resolution of laser induced purpura.

METHODS: In this randomized, double-blinded, placebo-controlled split-face study, 20 subjects with bilateral facial telangiectasia were treated with a pulsed dye laser (PDL) device at purpuric settings. The test articles, a gel containing vitamin K oxide and placebo (vehicle), were each randomly assigned to one side of the subject’s face. Subjects applied the test articles twice a day for the following 9 +/- 1 days. Improvement in both focal and general field purpura on each side of the face was assessed by the investigator using photographs. A scale of -100% (worsening) to 100% (improving) was used to rate photos against a baseline photograph obtained 15-30 minutes after treatment with the PDL device.

RESULTS: Resolution of the field of purpura was consistently greater with the vitamin K oxide gel after the second day of treatment. The greatest difference between the vitamin K oxide gel and placebo scores occurred on the fourth day after treatment. Although differences in active versus placebo scores did not reach statistical significance during the nine-day study period, a trend toward faster resolution of purpura with the active product was seen. Treatment-related adverse effects were not observed in any subject.

CONCLUSION: Vitamin K oxide gel appears to hasten the resolution of pulsed dye laser-induced purpura in subjects being treated for bilateral facial telangiectasia, and may well be useful in accelerating resolution of facial bruising from other cosmetic procedures such as fillers used for soft-tissue augmentation as well as other types of cutaneous surgical procedures

As there are so few genuine treatments for the redness of rosacea, the availability and promotion of Vitamin K Oxide may lead to some interesting and useful options for rosacea sufferers.

Highlighted Product

Related Articles

• PSF reduces the pain of Pulsed Dye Laser
• How to cure a red face
• pain, swelling and redness after pulse dye laser treatments
• Photoderm Blisters: First, Do No Harm
• rosacea swelling relief regime
• arnica montana for swelling and bruising
• allergic reaction to Vitamin K  & Vitamin E

News today that Sol-Gel Technologies has filed for Investigational New Drug for a product they are calling DED45-EV. This topical gel is targeted as a treatment for rosacea.

There doesn’t seem to be other copies of this release, or related information so this could just be a pure PR exercise.

The exact details of the active ingredients in this product are not being made public. So far, only PR speak along the lines of ““As Sol-Gel’s microcapsulation forms a protective barrier between the drug and the skin, we expect it to reduce irritation when applied to the relatively sensitive skin of rosacea patients,“said Dr. Stanley Shapiro, Sol-Gel’s Head of Skin Care Science & Technology.” is being published.

My guess back in July in Sol-Gel Trialling Benzoyl Peroxide (DER 45 EV) for Rosacea ? was that this topical gel was in fact benzoyl peroxide. Certainly the publicity so far from Sol-Gel has been related to acne and acne treatments.

Sol-Gel Anti-Acne Clinical Study Shows Significantly Improved Efficacy and Safety

“In the Sol-Gel kits, the proprietary silica microcapsules encase and continuously release the benzoyl peroxide, enabling a significant increase in efficacy and tolerance in comparison to products containing free benzoyl peroxide

As I said in July, many rosacea sufferers will know from their own experiences, many acne treatments are just too harsh for their sensitive rosacea skin.

If anyone sees some more information that confirms the makeup of DER45-EV please do let us know.

Related Articles

• Business Wire: Sol-Gel’s IND Application for Rosacea Accepted by FDA
• Sol-Gel Trialling Benzoyl Peroxide (DER 45 EV) for Rosacea ?

A newly filed patent contains a proposed rosacea treatment using small bands of infrared radiation between 790nm and 900nm with a power between 1 and 100 mW/cm^2. The unit proposed could be a LED device, used from twice a day to every 10 days. An energy density between 3 and 180 Joules/cm^2 is proposed.

Infrared Light is in the invisible spectrum below red, with wavelengths from 700nm to 2,000nm. We know that infrared light penetrates skin tissue more effectively than visible light.

An example device described is the OMNILUX Plus, which is promoted as “(Infra-red) works as a combination therapy with the Revive (red) head for even better skin rejuvenation, ideal for deeper lines and wrinkles”. OMNILUX Plus is based on a matrix of Infra Red LEDs, which provide narrowband 830nm light. This device is not currently promoted as a treatment for rosacea, so it seems that this patent covers using an existing treatment method for a new condition – rosacea.

The example treatment regime used an OMNILUX Plus unit at 830nm (+/- 0.5nm), using 55 mW/cm^2 at a distance of 1-10cm from the skin for 20 minutes with a power of 66 Joules/cm^2, twice a week for four weeks. Goggles were used and the unit was further placed 3-5cm from the patient’s nose.

The patent says that the patient enjoyed substantially reduced telangiectasia and reduced inflammatory papules.

Treating erythematotelangiectatic rosacea or papulopustular rosacea with narrow-band infrared light radiation and radiation kits therefor

United States Patent Application 20090270847, Lee; Seung Yoon, October 29, 2009

A method of treating erythematotelangiectatic rosacea or papulopustular rosacea in a subject comprises exposing the subject’s skin in need thereof to narrow-band infrared radiation at a wavelength(s) in a range of between 790 nm and 900 nm and having a band width of between 0 nm and 20 nm, in an effective dose to treat erythematotelangiectatic rosacea or papulopustular rosacea and essentially not to cause photothermolysis of the skin. Alternatively, a method of treating erythematotelangiectatic rosacea or papulopustular rosacea in a subject comprises exposing the subject’s skin in need thereof to narrow-band infrared radiation at a wavelength(s) in a range of between 790 nm and 900 nm and having a band width of between 0.1 nm and 20 nm, in an effective dose to treat erythematotelangiectatic rosacea or papulopustular rosacea. A kit for such methods comprises a radiation source generating narrow-band infrared radiation at a wavelength(s) in a range of between 790 nm and 900 nm, the narrow-band infrared radiation having a band width of between 0 nm and 20 nm and having a power density of between 1 mW/cm^2 and 100 mW/cm^2, and a manual instructing a user how to use the narrow-band infrared radiation for treating erythematotelangiectatic rosacea or papulopustular rosacea.

Featured Product

Related Articles

• Handheld OMNILUX clear-U, red and blue LEDs together
• LED post laser helps recover from redness
• Red LEDs for acne and rosacea
• Infrared saunas • Rosacea Support Community
• LLLT – an overview • Rosacea Support Community

I can’t say that I know how much industry weight is carried by the publication Medical Marketing & Media, but they have awarded Galderma the Gold Award for `Best Individual Product Advertisement in Consumer Press’ for their marketing of Oracea.

Apparently, “in order to drive product demand, the ads needed to educate consumers about the disease state. They also needed to be sensitive to the fact that the condition upsets and frustrates patients.”

The campaign is further praised for `sensitive drawings of people with the condition and an illustration of how the product works under the skin at the root of the problem’.

Further praises included `demonstrating the condition without making it unnecessarily heavy’ and `very charming execution that would make a reader stop to read more.’

I guess it is kind of cute to promote the whole `works from within’ angle. If you want to see the print advertisement you can click on the graphic above or view the video version at oracea.com.

Even though Oracea is a delayed release form of already available treatment, it is clear that  Oracea is successfully creating it’s own market segment. In the year ended July 2009 Oracea was responsible for revenue of $104m. Additionally we know that 2 rival pharmaceutical companies, Impax Laboratories and Mylan Pharmaceuticals want to get a piece of the 30+10mg doxycycline market.

So what is Oracea, really ?

I find it fascinating that a company can take an existing product, such as periostat, do some research and development, obtain a handful of patents, identify a market segment by targeting a disease not well serviced, and come up with a product we now know as Oracea.

The new owners of Oracea – Galderma, gladly added Oracea to their rosacea portfolio that already included another of the rare rosacea targetted prescriptions – metrogel.

Of course it is a massive venture to get a new drug through the FDA, but so far it looks like the venture has paid off financially.

All of this despite being able to make an argument that Oracea is comparable to 50mg a day of generic doxycycline.

Related Articles

• Is Oracea different to 50mg doxycycline ?
• Oracea too expensive ?
• Oracea worth $104m a year, good news for Sansrosa

Galderma announced in February a new SPF 50 Facial Sunscreen called Cetaphil UVA/UVB Defense SPF 50. Actually Galderma is not promoting this product as a sunscreen, but as a facial moisturizer.

Said to be non-greasy and hydrating, the UVA/UVB Defense SPF 50 contains 4 chemical filters as well as micronized titanium dioxide to offer a very high sun protection factor of 50. Thus the Defense 50 contains both chemical and physical sun protecting factors.

The Cetaphil range of moisturizers and cleansers are reasonably well tolerated and liked by rosacea sufferers. My daily regime still includes the Gentle Skin Cleanser and Moisturizing Lotion.

Although some rosacea sufferers may not be able to tolerate the chemical sunscreens in this product, it is good news for those who can because the Cetaphil range of products are easily available and generally quite affordable.

The web site for the Cetaphil UVA/UVB Defense SPF 50 lists the following components

Active Ingredients: Octinoxate 7.5%, Octisalate 5%, Octocrylene 7%, Oxybenzone 6%, Titanium Dioxide 5.7%

Inactive Ingredients: Water, Propylene Glycol, Glycerin, Dimethicone, VP/Eicosene Copolymer, Cyclohexasiloxane, Stearic Acid, Potassium Cetyl Phosphate, Glyceryl Stearate, PEG-100 Stearate, Aluminum Hydroxide, Dimethiconol, Disodium EDTA, Tocopherol, Cyclopen-tasiloxane, Triethanolamine, Phenoxyethanol, Ethylparaben, Chlorphenesin, Cetyl Alcohol, Acrylates/C10-30 Alkyl Acrylate Crosspolymer, Methylparaben, Xanthan Gum

What do YOU think ?

This product doesn’t appear to have been used by many rosacea sufferers to date.

The Cetaphil UVA/UVB Defense SPF50 reviews at amazon.com do suggest that users are liking the high sun protection offered, as well as the product being quite moisturizing and easy to apply.

If rosacea sufferers can get past the 4 chemical sunscreens in this product then it may well become a good choice for when you need super sun protection.

Featured Product

Related Articles

• cetaphil moisturizing cream helps rosacea dry skin
• Cetaphil Gentle Cleansing Bar well tolerated, even helps rosacea
• cetaphil gentle skin cleanser well tolerated
• what is the best moisturizer for rosacea ?
• the best moisturisers with sunscreen
• CeraVe Hydrating Cleanser and CeraVe Moisturizing Lotion

So please feel free to start your own Rosacea Community Blog.

Why would I want one of those ?

Your own blog will allow you post your thoughts, ideas, rants etc. in a part of the community site that you can call your own. Each post will be stored and given its own unique web address, stored underneath your Rosacea Support Community Username.

Getting Started

To get started, just login and look for the link titled “My Blog” near the top right hand side.

Writing a blog post feels very much like writing a forum posting. Just select “Post a Blog Entry’ and you are underway. Type a good descriptive Subject, your post text and hit Submit.

Once you have posted a blog entry, other users will be able to comment on your post.

Other Blogs

You can see what others are saying on their blog my taking the link to Blogs, also on the top right hand side.

You will also notice a new link above the forum index called “View blog posts” that will show you who has posted an entry recently.

Once a user has posted some blog entries, you’ll see a link below their profile.

What is allowed ?

Basically anything that is and isn’t allowed on the community forum, will also be allowed or frowned upon on the Community Blogs. Any post that seeks to build friendships and uplift rosacea sufferers will be fine.

How do I register ?

Not a member of the Rosacea Support Community ? No problem, just Register here.

Already registered ? Great, what are you waiting for ? Start your Rosacea Community Blog now.

Dr. Mannis in his interview for the RSRP had this to say about IPL and ocular rosacea.

Q: Do you think IPL treatment of the face usually improves ocular rosacea? What about patients who feel that it has made their ocular rosacea worse, eg more veins showing in the white of the eye, lids more sensitive, eyelashes falling out, hot compresses now cause the eyes to swell?

A: Unfortunately, as ophthalmologists, we have very little experience with IPL. That’s something that’s done by and large by dermatologists. I am not aware of any definite ocular side effects from facial treatments with IPL.

Q: Does ocular rosacea increase the likelihood of cataracts or other eye diseases such as macular degeneration, or central serrous corinopathy (retinopathy)?

A: No. But, if IPL is done, there needs to be eye protection. Any kind of laser treatment done on the skin around the eye requires the practitioner to use eye shields to be sure that the globe is not exposed to the intense light in any way. As long as it’s not, then the likelihood of any of those problems occurring is very small.

For more information on Dry Eye see the following articles: Dry Eye: Awareness, Diagnosis, and Management and Dry Eye Syndrome from Sunday Times Sri Lanka

Zapping Dry Eye

Posted: 12:23 pm EDT October 8, 2009

Christopher Coad, M.D., Ophthalmologist at Chelsea Eye & Cosmetic Surgery Associates in New York City, is using a technique for some dry eye patients called intense pulsed light therapy (IPL). IPL is sometimes used to reduce facial skin redness caused by growth of abnormal blood vessels in patients with rosacea. Doctors noticed that some rosacea patients reported easing of dry eye symptoms after getting IPL. That finding led physicians to try it for patients with dry eye.

First, eye shields and a cooling ultrasound gel are placed around the eyes to protect the eyes and surrounding skin. Then, the IPL is aimed under the lower lid, moving across the eyes. Two passes of the light are made. Then the gel and eye shields are removed.

Coad says IPL has three main effects on dry eye. First, the heat acts like a warm compress to liquefy the blocked oil that’s plugging the meibomian gland. Second, the small blood vessels that carry inflammatory cells to the site are sealed. Third, the light treatment improves the health and function of the meibomian gland, reducing the risk of further inflammation.

Related Articles

• claritin, zyrtec and dry eyes
• Dry Eye: Awareness, Diagnosis, and Management
• dry eye and linoleic acid
• Dry Eye Syndrome from Sunday Times Sri Lanka
• cyclosporine (restasis) shows promise for ocular rosacea

Zoe Draelos MD is listed as a contact for the trial. Dr. Draelos is well known to rosacea sufferers. You can read some more of her research via the popular Rosacea News items: cleansing and the management of rosacea, finacea is good for acne and hyper pigmentation as well, and cetaphil gentle skin cleanser well tolerated.

Not a lot can be found on the internet about the company or the product mentioned in this trial. It seems that Topical Dissolved Oxygen has been trialled as a wound healing stimulant – an alternative to hyperbaric chamber therapy. If you have any more information, please post in the comments below.

The Role of Topically Dissolved Oxygen (TDO) to Ameliorate Signs of Photodamage

This study is an evaluation of the role of topical dissolved oxygen to lessen visible signs of photodamage using a select regimen of topical dissolved oxygen containing cosmeceutical products. Evaluation of the overall skin tolerability of topical dissolved oxygen (safety) utilizing the regimen of products.

Related Items

• reapply sunscreen to avoid skin damage
• photo rejuvenation with IPL