As the trial is for the redness of rosacea, and Allergan bought Vicept Therapeutics in 2011, it is clear that AGN-199201 is the Oxymetazoline based product previously known as V-101.

Who are Allergan?

The new owners of V-101 are Allergan who are perhaps better known for making the dry eye treatment Restasis, Refresh artificial tears, and the product that was the genesis of Sansrosa – Alphagan P. Allergan are also the makers of Aczone.

What is Oxymetazoline

Oxymetazoline is the active ingredient in decongestant products like Afrin, Sudafed OM and Vicks Sinex as well as in eye drops like Visine LR.

A well known side effect of Visine is rebound redness, where continued use leads to the redness that you were originally treating. Extended usage of Afrin can also lead to rebound nasal congestion.

Safety and Tolerability of AGN-199201 in Patients With Erythema Associated With Rosacea

Clinical Trial NCT01579084

Phase 1

Primary Outcome Measures: Percentage of Patients with at Least a 2-grade Decrease from Baseline on Both Clinician Erythema Assessment (CEA) and Subject’s Self Assessment (SSA)

Drug: AGN-199201 Formulation A and B
Drug: AGN-199201 Formulation B and C
Drug: AGN-199201 Formulation C and A
Drug: AGN-199201 Formulation A and AGN-199201 Vehicle
Drug: AGN-199201 Formulation B and AGN-199201 Vehicle
Drug: AGN-199201 Formulation C and AGN-199201 Vehicle
Drug: AGN-199201 Formulation A
Drug: AGN-199201 Formulation B
Drug: AGN-199201 Formulation C
Drug: AGN-199201 Vehicle

Related Articles

• FDA gets tough with Allergan over Aczone
• Allergan buys Aczone, has plans for rosacea targeting ?
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The positive results from the study were based on the participants own clinical subject signs ie. how they rated their own stinging, discomfort, tightening and heat sensations. Uriage Thermal Water was able to show a statistically significant reduction in stinging sensations.

We are not told about any results for any reduction in the objective measures: erythema, edema and scaling. Even though the poster title mentions Facial Redness, the quoted results don’t specifically mention any reduction in erythema.

I’d say these results are on the weak side but could be interesting for those who want to try something like UTW.

Poster reference number 5011

Facial redness: Diagnosis and adjuvant topical use of thermal water in a series of 232 cases

American Academy of Dermatology 70th Annual Meeting, March 16–20, 2012, San Diego, California. Poster Abstracts, Supplement to JAAD, April 2012, Volume 66, Number 4.

Marius Anton Ionescu, MD, PhD, Dermatology Polyclinic, Saint-Louis Hospital, Paris, France; Luc Lefeuvre, PhD, Laboratoires Dermatologiques d’Uriage, Courbevoie, France; Michel Bohbot, PhD, Laboratoires Dermatologiques d‘Uriage, Courbevoie, France

Background: Uriage thermal water (UTW) is prescribed as topical adjuvant in post laser treatments or in chronic skin conditions as rosacea, atopic dermatitis.

Purpose: To assess the dermatologic entities included usually in the term of ‘‘facial red skin’’ and the benefit of UTW in the management of these conditions.

Methods: This open multicenter study (51 dermatologists) included adult patients consulting for a facial inflammatory, irritant or allergic skin condition (‘‘red skin’’).

UTW was prescribed in monotherapy or in association with dermocosmetic care or medical treatment. UTWwas applied for 4 weeks, with 2 examinations (baseline and week 4).

Clinical subjective criteria (stinging, discomfort, ‘‘tightening,’’ and ‘‘heat’’ sensations) and objective (erythema, edema, and scaling) were followed (scores from 0 [absent] to 4 [severe]).

Results: We included 232 patients, 81.6% female, 18.3% male, mean age 44. Fitzpatrick phototypes were: II, 50.2%; III, 35.9%; I and IV, 13.9%. The diagnosis and indications for the use of UTW were: rosacea 36.2%, postlaser 14.3%, seborrheic dermatitis 11.4%, post-dermosurgery procedure (peeling, fillers, electrocoagulation, and phototherapy) 10.5%, contact dermatitis 15.7%, atopic dermatitis 4.8%, postdermatologic treatment (AHA or isotretinoin) 3.3%, other 3.8%. UTW was prescribed in monotherapy in 52% of cases and in association with other treatments in 48%.

Clinical subjective signs were significantly improved after UTW use in monotherapy at week 4 compared to baseline (P<.001).

Self-assessment showed an improvement of ‘‘stinging’’ sensations in 80% of patients and a ‘‘soothing sensation’’ in 87%.

Skin tolerance was good to excellent in 96.6% of cases.

Conclusion: In this series of 232 patients with a diagnosis of ‘‘facial red skin’’ (postlaser, rosacea, or seborrheic dermatitis), UTW decreased significantly clinical subjective signs (P<.001).

Commercial support: 100% by Laboratoires Dermatologiques d’Uriage.

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No searching could find a product from L’Oreal that contained the following ingredients;

• palmitoyl tripeptide-8
• epurea extract
• bisabolol
• caffeine
• zinc gluconate

So it would appear that this is a new product under development from L’Oreal. This is potentially very good news for rosacea sufferers.

If you find the name of this product please let us all know in the comments below.

Rosacea sufferers will be aware that Rosacea heavyweight Galderma started life in 1981 as a joint venture between L’Oreal and Nestle.

Poster Session 5554

Clinical evaluation of the effectiveness and tolerance of a facial lotion on subjects with rosacea

American Academy of Dermatology 70th Annual Meeting, March 16–20, 2012, San Diego, California. Poster Abstracts, Supplement to JAAD, April 2012, Volume 66, Number 4.

Susana Raab, L’Oreal Research and Innovation, Clark, NJ, United States; Christian Oresajo, L’Oreal Research and Innovation, Clark, NJ, United States; Margarita Yatskayer, L’Oreal Research and Innovation, Clark, NJ, United States; Zoe Draelos, MD, Duke University School of Medicine, Durham, NC, United States

Background: Rosacea is a chronic skin condition involving inflammation of the cheeks, nose, chin, and forehead. It causes redness, flushing, and inflammatory papules. Subjects with rosacea have sensitive skin that is easily irritated by skin care products. There is a need for a topical product that reduces the signs and symptoms of rosacea without exacerbating the disease.

Methods: This study evaluates a facial lotion formulated with palmitoyl tripeptide-8, epurea extract, bisabolol, caffeine and zinc gluconate, in female volunteers with mild to moderate facial rosacea and the presence of a minimum of three inflammatory papules.

This clinical study included 50 female subjects between the ages of 25 and 60 with evaluations at baseline, postapplication, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after product application.

For the duration of the study, volunteers used the facial lotion twice daily, and continued using any rosacea medications provided the type and dosage was stable for 3 months prior to study participation.

Evaluations were performed by a board-certified dermatologist and included objective and subjective tolerance grading, clinical efficacy grading of facial skin attributes for redness, flushing, smoothness, radiance, skin tone evenness, overall appearance, and rosacea severity using a 5-point ordinal scale.

Lesion counts, noninvasive bioinstrumentation to assess transepidermal water loss (TEWL), hydration and skin redness, subject self-assessment questionnaires, and digital photography were also included in the study.

Results: The results of this study showed significant improvements in redness, flushing, smoothness, radiance, overall appearance and
rosacea severity. The results showed a significant reduction in lesion count at all time points when compared to baseline.

There was a statistically significant drop in facial redness at week 4 and the TEWL measurements remained steady throughout the study demonstrating that the lotion is a gentle to the skin. Tolerance evaluations indicated the facial lotion was well tolerated by the study  panel.

Commercial support: 100% is sponsored by L’Oreal Research and Innovation.

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• L’Oréal strong sales via Galderma and dermatology
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These latest large scale trials were able to confirm the positive findings resulting from the Phase II trials.

This must be a great relief to Galderma who had to return to Phase II trials after previously commencing Phase III trials.

March 16, 2012 08:00 ET

Galderma Announces Completion of Phase 3 Trials of Investigational Drug Targeting Facial Erythema of Rosacea

FORT WORTH, TX–(Marketwire – Mar 16, 2012) – Galderma Laboratories, L.P. today announced the completion of two independent Phase 3 clinical trials that evaluated the efficacy and safety of CD07805/47, a proprietary topical gel under investigation in adults with moderate to severe facial erythema (redness) of rosacea. Rosacea is a chronic, inflammatory and vascular condition of the face and eyes characterized by persistent erythema, flushing, inflammatory lesions and visible blood vessels that affects at least 16 million Americans and with estimates of prevalence ranging from less than 1% to more than 20% of the adult population in other countries globally.

The results of the two randomized, vehicle-controlled, multicenter Phase 3 trials that investigated the efficacy and safety of CD07805/47 applied topically once daily vs. vehicle (control) in adult patients with moderate to severe facial erythema of rosacea confirmed results observed in prior Phase 2 studies.

…

Galderma intends to submit a New Drug Application for CD07805/47 to the U.S. Food & Drug Administration and to the European Medicines Agency.

When Will Sansrosa Be Available?

Best answer: No ones knows. There are just too many things still to be decided. It may never even get to market. My guess at the earliest you might see Sansrosa available is mid 2014. I reserve the right to push this date out at any time and please note that mid 2014 is still a pretty hopeful date.

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A product from Merck designated as MK-0524, also known as Laropiprant, is to be trialled as a treatment for the redness of rosacea.

This is great news for rosacea sufferers as MK-0524/Laropiprant will now join Sansrosa and Oxymetazoline which are already in development for this mostly ignored group of rosacea symptoms.

Trialists will take either Lapropiprant or placebo once daily for 4 weeks and be assessed on any reduction in the erythema, or redness associated with rosacea.

Laropiprant is a selective prostaglandin-2 receptor inhibitor, and is believed to specifically target the cascade of events causing flushing.

When taken in combination with Niacin, Laropiprant is used to treat high cholesterol. Niacin on its own would be generally considered unsuitable for rosacea sufferers because of the unwanted side effect of inducing facial flushing. Laropiprant itself has no cholesterol lowering effect, but it reduces facial flushes induced by niacin. The trial specifically excludes anyone who is currently taking more than 500mg a day of Niacin.

To date Merck have not had a product that could be called a rosacea treatment.

Clinical Trial NCT01451619

A Study of Laropiprant (MK-0524) in Participants With Moderate to Severe Erythematotelangiectatic Rosacea (MK-0524-155)

This study will assess the effect of MK-0524 relative to placebo, on signs and symptoms of rosacea and to determine the safety and tolerability profile of MK-0524 in participants with rosacea

A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel Group Study to Assess the Pharmacodynamics of MK-0524 in Subjects With Moderate to Severe Erythematotelangiectatic Rosacea. (Protocol No. 155)

Trial participants are expected to use effective forms of contraception during the trial and may not have more than 5 papules/pustules. The full list of exclusions further suggests that this drug can have significant side effects.

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• How to Cure a Red Face (facial erythema or redness)

Steroid Induced Rosacea is, sadly, one hot topic.

I know this because the blog posting Treating Steroid Induced Rosacea is one of the most visited pages on this site, and is currently approaching 1000 comments. Unfortunately many who find themselves suffering from steroid rosacea have to endure a prolonged withdrawal and recovery period.

This just published abstract relating to Steroid Induced Rosacea is interesting for a few reasons;

• The average period of treatment for these steroid using patients was 20 months.
• The majority were using potent steroids (but we also know that OTC Steroids can cause Steroid Rosacea).
• The majority were using steroids for what the authors claim to be trivial dermatoses.

Could it be the case that vanity is driving some of the suffering that occurs from steroid rosacea?

I wonder if anyone who is suffering from the angry red face of steroid withdrawal would be so quick to use steroids if they had known where it could lead?

The paper ends with the conclusion that oral antibiotics and topical tacrolimus (Protopic) is the treatment of choice.

Steroid-induced rosacea: a clinical study of 200 patients, Indian J Dermatol. 2011 Jan;56(1):30-2, Bhat YJ, Manzoor S, Qayoom S.

Department of Dermatology, SKIMS Medical College Hospital, Srinagar, Jammu and Kashmir

BACKGROUND: Topical corticosteroids were first introduced for use in 1951. Since then uncontrolled use (abuse) has caused many different reactions resembling rosacea – steroid dermatitis or rosacea. Multiple pathways including rebound vasodilatation and proinflammatory cytokine release have been proposed as the mechanism for such reactions.

AIM: The aim was to study the adverse effects of topical steroid abuse and the response to various treatment modalities.

MATERIALS AND METHODS: Two hundred patients with a history of topical steroid use on face for more than 1 month were studied clinically and various treatments tried.

RESULTS: The duration of topical corticosteroid use varied from 1 month to 20 years with an average of 19.76 months. Majority of patients were using potent (class II) topical steroids for trivial facial dermatoses. The common adverse effects were erythema, telangiectasia, xerosis, hyperpigmentation, photosensitivity, and rebound phenomenon. No significant change in laboratory investigations was seen.

CONCLUSION: A combination of oral antibiotics and topical tacrolimus is the treatment of choice for steroid-induced rosacea.

It is Time to Taper!

If you are using steroid creams regularly then this abstract should serve as some good advice to think about tapering off. Don’t withdraw cold turkey style, but taper off instead. See if you can find a doctor to support you.

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A Press Release today (Vicept are happy to generate publicity at every step of their development) touting more Phase II Study results for their Oxymetazoline based V-101 product. V-101 is a topical slated to treat the redness of rosacea.

The first Phase II trial results for V-101 were announced just 3 months ago.

It isn’t yet clear what Vicept Therapeutics have done with the commonly available active ingredient oxymetazoline to package it as palatable to the sensitive skin of rosacea sufferers.

This most recent study `was designed to optimize the concentration of V-101 Cream in preparation for Phase III clinical testing in patients with erythematous rosacea and to further characterize the duration of the clinical effect’.

The previous Phase II trial examined 4 concentrations but this latest trial evaluated 2 concentrations of the active ingredient in V-101.

Vicept Therapeutics are now pushing for a meeting with the FDA to seek permission to enter into Phase III evaluations.

Vicept Therapeutics Announces Positive Results from a Second Phase II Study of V-101 for the Treatment of Type I Rosacea (Erythematotelangiectatic Rosacea)

Malvern, PA – April 19, 2011

Vicept Therapeutics, Inc. announced today positive results from a second Phase II clinical trial evaluating the dose-response relationship of two concentrations of V-101 cream, a topical cream for the treatment of Type I Rosacea (Erythematous Rosacea).

The results demonstrated a statistically significant improvement (p= <0.01) in the primary endpoint, a reduction in facial erythema or redness, over a twelve hour period versus placebo cream in patients with erythematous rosacea.

Further, V-101 demonstrated a safety profile similar to placebo cream. This is the second of two V-101 Phase II studies to achieve statistical significance in the primary endpoints.

Related Patents

See Vicept Therapeutics gets funding for V-101 for coverage of the Patents owned by Vicept relating to their Oxymetazoline based treatment.

What About Rebound Redness?

There is still a question in my mind about how in-development treatments like V-101 will deal with the possibility of rebound redness.

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A brief extract today covering a paper detailing how the topical Xylometazoline can be used to treat the redness of rosacea.

Similar to oxymetazoline, xylometazoline is marketed as a nasal decongestant under many brand names. Brands you may come across include Otrivine, Otrivin, Sinutab Nasal Spray, Cirovin and Novorin.

Oxymetazoline is the active ingredient in over the counter products such as Afrin, Vicks Sinex and Visine. The potential side effects of oxymetazoline when applied topically include rebound redness, hypertension and palpitation.

We know that both oxymetazoline and xylometazoline are fast acting topical decongestants and that their effects are similar. Oxymetazoline was developed from Xylometazoline in 1961.

Caution

Even though the active ingredient discussed in this paper is readily available as a nasal decongestant, it doesn’t follow that applying Otrivin topically is a good idea. There are many other ingredients in these topicals that may be irritating to rosacea skin. Also you cannot be sure that you are applying the correct amount when you use a spray topically. Finally, the long term effects of the metazolines on skin won’t be known until a lot more research and trials are completed.

Some Good News

What is encouraging, though, is the fact that more researchers are looking at the metazoline family and that new treatments for the redness of rosacea are on the horizon.

Rosacea (erythematotelangiectatic type) effectively improved by topical xylometazoline.

J Dermatol. 2010 Nov 3. doi: 10.1111/j.1346-8138.2010.00999.x.

Kim JH, Oh YS, Ji JH, Bak H, Ahn SK., Department of Dermatology Institute of Basic Medical Science, Yonsei University Wonju College of Medicine, Wonju Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

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We were tipped off by a comment on the blog posting about Cutanix going offline, to the possible future availability of a Cutanix like product. The commenter, who works for SkinMedica told us that;

skincarejunkie

Bioform was sold to Merz Aesthetics.
In that sale Cutanix was sold to SkinMedica.
They will launch the product this Jan so stay tunned!

The last news from Cutanix was in April 2007 when they disappeared off the internet and a warning letter from the FDA surfaced. At that stage DRL was a part of my regular regime, it kept my facial redness under pretty good control. I, along with many others was sad to hear that this product was no longer available.

Now SkinMedica has announced the availability of their formulation of the Cutanix DRL, as a new product called Redness Relief Calmplex Treatment Moisturizer.

This product is available in 1.6 ounces (50ml / 45gm) for $80 at skinmedica.com.

By comparison we have been used to paying $45.00, or less with a discount, for 1.7 oz of Cutanix DRL.

How to Purchase

SkinMedica products are available at physician offices across the US. You can use their Physician Finder to find one close to you. Alternatively you can purchase RR CalmPlex from their web site and designate any physician when you place your order.

Ordering outside the US is to be possible via the international distributors for SkinMedica.

Does it Work ?

The Redness Relief Camplex contains the same active ingredient from the Cutanix Dynamic Relief Lotion, namely 4-Ethoxybenzaldehyde. SkinMedica call this ingredient CalmPlex. Cutanix’s moniker was Quadrinone.

SkinMedica tell us that they have commissioned Dr. Zoe Draelos to undertake pilot studies into the effectiveness of Redness Relief CalmPlex and that the results of these studies are on file at SkinMedica. Of course not being able to read this studies does mean that we can’t see for ourselves how effective is has proven to be. Perhaps in the future more research will become available.

The publicity for RR CalmPlex also tells us that in in-vitro (i.e. in the lab, not on skin) CalmPlex was found  to be an inhibitor of Prostaglandin E2 (PGE2), claimed to be a key natural vasodilator.

A small pilot study published in 2005 concluded that this benzaldehyde-derived anti-inflammatory agent may be useful in reducing facial erythema in a rosacea model.

Redness Relief CalmPlex Ingredients

Water/Aqua/Eau, Glycerin, Ethoxydiglycol, Squalene, Isocetyl Stearate, Simmondsia Chinensis (Jojoba) Seed Oil, Isostearyl Palmitate, Mineral Oil, Glyceryle Stearate, PEG-100 Stearate, Niacinamide, Glycereth-7, PEG-7 Glyceryl Cocoate, 4-Ethoxybenzaldehyde (CalmPlex), Cetyl Ricinoleate, Polysorbate 20, Polyacrylamide, C13-14 Isoparaffin, Laureth-7, Phenoxyethanol, Methylparaben, Propylparaben, Butylparaben.

Defunct Cutanix DRL Ingredients

By comparison, here are the Cutanix DRL Ingredients. Note that Cutanix referred to 4-Ethoxybenzaldehyde  as Quadrinone.

Purified Water, Glycerin, Ethoxydiglycol, Glyceryl Stearate (and) PEG 100 Stearate, Squalane (vegetal), Isocetyl Stearate, Isostearyl Palmitate, Simmondsia Chinesis (Jojoba) Seed Oil, Lipovol MOS-130, Niacinamide, Glycereth-7, PEG-7 Glyceryl Cocoate, Polyacrylamide (and) C13-14 Isoparaffin (and) Laureth-7, Quadrinone, Cetyl Ricinoleate, Phenoxyethanol (and) Methylparaben (and) Ethylparaben (and) Butylparaben (and) Propylparaben (and) Isobutylparaben, Polysorbate-20

Are you Excited?

I can well remember the sad thoughts when Cutanix was no longer available. Will you be tempted back to try RR CalmPlex?

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One of the up and coming treatments for the redness of rosacea is the use of oxymetazoline based formulations.

Oxymetazoline is the active ingredient in decongestant products like Afrin, Sudafed OM and Vicks Sinex as well as in eye drops like Visine LR.

Recent publicity from Vicept Therapetics suggests that their product in development V-101 contains the active ingredient oxymetazoline.

A well known side effect of Visine is rebound redness, where continued use leads to the redness that you were originally treating. Extended usage of Afrin can also lead to rebound nasal congestion.

Rebound redness with eyedrop use

PEOPLE’S PHARMACY

Oxymetazoline is a long-acting topical drug that constricts, or shrinks, blood vessels. That is how it relieves congestion in the nose. But people who use nasal decongestants for allergies, colds or sinus problems are warned to use such products for only three to five days. After that they may experience rebound congestion as the medicine wears off.

The same thing can happen in the eyes. Rebound redness occurs when the blood vessels dilate after the effects of the medicine fade. It can take several days (or sometimes longer) for this effect to gradually disappear. You may be better off with artificial tears rather than anti-red drops.

For any oxymetazoline based treatment to succeed as a treatment for a chronic condition like rosacea (i.e. rosacea isn’t a condition that goes away after just a couple of days), the promoters will need to prove that their formulations are safe for use in the medium to long term.

A 2007 paper Successful Treatment of the Erythema and Flushing of Rosacea Using a Topically Applied Selective α1-Adrenergic Receptor Agonist, Oxymetazoline attempted to answer this questions thus;

Neither of our patients exhibited either problem with the application of oxymetazoline to the skin. While the laboratory induction of receptor desensitization cannot yet be perfectly correlated with actual physiologic response, recent laboratory studies indicate that agonists that are more selective for α1D-adrenoceptors are less prone to induce receptor desensitization than are α1A- or α1B-agonists. The clinical significance of this may be an important consideration in contemplating any potential future use of these drug classes on the skin because agonists with certain receptor subtype binding profiles may retain their clinically desirable effects while minimizing their adverse effect.

(emphasis mine)

You can download a full copy of this article from the Archives of Dermatology website; Successful Treatment of the Erythema and Flushing of Rosacea Using a Topically Applied Selective α1-Adrenergic Receptor Agonist, Oxymetazoline

So we all wait to see how the trials of V-101 prove performance with extended and intermittent usage of oxymetazoline.

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