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 ?
• Allergan buying Vicept Therapeutics to get V-101 / Oxymetazoline

This latest confirmation comes from the World Heath Organisation’s International Clinical Trials Registry Platform Search Portal. The search for CD5024 reveals trials that have completed in the Czech Republic, Germany and Hungary. The register was created in 2006, the same year as when CD5024 was trialed in Australia.

EUCTR2006-001999-20-CZ

ASSESSMENT OF THE EFFICACY AND SAFETY OF THREE CONCENTRATIONS: 1%, 0.3%, 0.1% OF CD5024 CREAM ONCE DAILY AND CD5024 1% CREAM TWICE DAILY, VERSUS ITS VEHICLE AND VERSUS METRONIDAZOLE 0.75% CREAM (ROZEX®), IN PATIENTS WITH PAPULO-PUSTULAR ROSACEA OVER 12 WEEKS

Intervention(s)

Product Name: CD5024

Product Code: CD5024

Pharmaceutical Form: Cream

INN or Proposed INN: IVERMECTIN

CAS Number: 70288-86-7 Current Sponsor code: CD5024 Other descriptive name: ANTI PARASITIC Concentration unit: % percent Concentration type: equal Concentration number: 1% Pharmaceutical form of the placebo: Cream Route of administration of the placebo: Cutaneous use Product Name: CD5024 Product Code: CD5024 Pharmaceutical Form: Cream

INN or Proposed INN: IVERMECTIN CAS Number: 70288-86-7 Current Sponsor code: CD5024 Other descriptive name: ANTI PARASITIC Concentration unit: % percent Concentration type: equal Concentration number: 0.3% Pharmaceutical form of the placebo: Cream Route of administration of the placebo: Cutaneous use Product Name: CD5024 Product Code: CD5024 Pharmaceutical Form: Cream

INN or Proposed INN: IVERMECTIN CAS Number: 70288-86-7 Current Sponsor code: CD5024 Other descriptive name: ANTI PARASITIC Concentration unit: % percent Concentration type: equal Concentration number: 0.1%

Pharmaceutical form of the placebo: Cream Route of administration of the placebo: Cutaneous use Trade Name: Rozex 0.75% Crème Product Name: METRONIDAZOLE (ROZEX®) Pharmaceutical Form: Cream INN or Proposed INN: METRONIDAZOLE CAS Number: 443-48-1 Other descriptive name: ANTI BACTERIAL Concentration unit: % percent Concentration type: equal Concentration number: 0.75-

Related Articles

• Massive Rosacea Study (CD5024) Recruiting Underway
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A recent press release teases rosacea sufferers that a topical foaming form of minocycline might become a new treatment.

The trial results promoted in the press release are for a condition called Impetigo, a bacterial skin infection.

Minocycline, as a member of the tetracycline family may offer some anti-inflammatory benefit to rosacea sufferers, but the question remains as to whether this benefit can be seen via a topical application. Minocycline is an unstable chemical and thus far has only been suitable as a systemic treatment – topical treatments have not been readily available.

Foamix Minocycline and Rosacea

We learnt in 2010 that a Phase II clinical trial was underway to examine whether a topical form of minocycline could help with rosacea. This trial NCT01134991 is due to complete in March 2012.

Foamix Impetigo Press Release

Foamix’s Minocycline Foam – 100% Effective in Impetigo Phase II Clinical Trial With No Side Effects – 80% Improved Significantly After 3 Days of Treatment

REHOVOT, Israel, March 14, 2012 /PRNewswire via COMTEX/ — Foamix, a clinical stage specialty pharmaceutical company, announced today the successful completion of the Phase II clinical trial of Minocycline foam in Impetigo patients. Minocycline Foam has shown to be highly effective against bacteria, including some multi-drug resistant strains (such as MRSA).

…

"These results are excellent; especially considering this study is the first to treat patients with topical Minocycline. The results confirm the efficacy of our Minocycline Foam in skin infections. It is also significant that our Minocycline Foam was well-tolerated and that there was no evidence of clinical safety concerns since one of the persistent barriers to the development of new classes of antibiotics has been the issue of patient safety," commented Dov Tamarkin, Foamix CEO. "We intend to aggressively pursue the development of our Minocycline Foam as a first-line treatment for a range of skin conditions, including Acne, Rosacea, Impetigo and other skin infections."

Key Features of Foamix’s Minocycline Foam

Minocycline is an extremely unstable compound, which currently exists only in oral dosage forms. Foamix successfully developed a stable, patient-friendly topical foam containing up to 4% Minocycline.

The topical administration of Minocycline Foam provides concentrated drug delivery to the infected lesion site, and leads to rapid cure, whilst avoiding the side effects common in the oral Minocycline treatment.

With a twice daily application, Minocycline Foam can lead to better patient compliance compared with other treatment options.

Foam is a user friendly dosage form which spreads evenly and absorbs easily without rubbing. This offers a great advantage when treating open wounds especially in small children.

Related Articles

• RSRP: Minocycline
• Foamix to Trial Foaming Topical Minocycline
• How do Tetracyclines Help Rosacea ?

In January 2009 we learnt that Medicis was interested in trialing Ziana as a treatment for rosacea. Medicis may be known to rosacea sufferers because they also make Plexion and Solodyn.

Sadly the rigorous nature of a clinical trial was not able to show that Ziana could reduce the papules and pustules of rosacea any better than the placebo.

Some Small Good News

The trial did find “nearly significant” (a hopeful term if I ever heard one) improvement in how the doctors perceived the broken blood vessels and also provable significant improvement in the redness associated with the rosacea symptoms.

Note also that participants experienced statistically significant increased facial scaling.

So overall not a great result for Medicis, whom I’m sure would have liked to been able to promote Ziana as an official treatment for the papules and pustules of rosacea.

User Reviews

Did you try Ziana ? Did you find any reduction in redness and facial blood vessels ? Would you recommend it ?

A randomized, double-blind, placebo-controlled, pilot study to assess the efficacy and safety of clindamycin 1.2% and tretinoin 0.025% combination gel for the treatment of acne rosacea over 12 weeks.

J Drugs Dermatol. 2012 Mar 1;11(3):333-9.

Chang AL, Alora-Palli M, Lima XT, Chang TC, Cheng C, Chung CM, Amir O, Kimball AB.

Background: Papulopustular acne rosacea is a chronic inflammatory condition which can be difficult to treat. Many patients are unwilling to use systemic medications, and single topical agents alone may not address all the symptoms of rosacea. A combination topical clindamycin phosphate 1.2% and tretinoin 0.025% gel is efficacious for acne vulgaris, and may be helpful for rosacea, since acne vulgaris and rosacea shares many similar clinical and histologic features.

Objective: To assess the preliminary efficacy and safety of a combination gel consisting of clindamycin phosphate 1.2% and tretinoin 0.025% on papulopustular rosacea after 12 weeks of usage.

Methods: Randomized, double-blind, placebo controlled two site study of 79 participants with moderate to severe papulopustular acne rosacea using both physician and subjects’ validated assessment tools. Primary endpoint consisted of statistically significant reduction in absolute papule or pustule count after 12 weeks of usage.

Results: There was no significant difference in papule/pustule count between placebo and treated groups after 12 weeks (P=0.10).

However, there was nearly significant improvement in physicians’ assessments of the telangiectasia component of rosacea (P=0.06) and erythematotelangiectatic rosacea subtype (P=0.05) in treated versus placebo group after 12 weeks.

The only significant adverse event different was facial scaling, which was significantly increased in treated group (P=0.01), but this did not result in discontinuation of study drug.

Conclusions: A combination gel of clindamycin phosphate 1.2% and tretinoin 0.025% may improve the telangiectatic component of rosacea and appears to better treat the erythemotelangiectatic subtype of rosacea rather than papulopustular subtype.

Our preliminary study suggests that future studies with much larger sample size might confirm our findings.

Clinical Trials: NCT00823901.

Related Articles

• Medicis readies to trial Ziana for rosacea
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A large study looking at a treatment for the papules and pustules of rosacea is looking to recruit participants right across the US and Canada.

A web site just for this study has been created at www.pprstudy.com (Papulo – Pustular – Rosacea Study). On the site you can use your ZIP code to see if there is a study location close to you.

As there is such a good overlap with study locations this publicity push looks to be for Trial NCT01493687.

Study  NCT01493687 is for Galderma’s mysterious CD5024 1% Cream and involves 45 locations and around 1360 participants.

My guess is that CD5024 is 1% Metrocream – seems reasonable that as the trial wants to compare against the “competition” in Finacea, the concentration is 1%, it is a Phase III trial, and the target is the papules and pustules of rosacea.

[update:] CD5024 is Ivermectin

I now believe that CD5024 is not Metronidazole. I speculated last year that Galderma might be looking at at topical Ivermectin preparations - Topical Ivermectin + Metrogel from Galderma and this page from the NHS UK seems to offer a clue as well – New Drugs Online – Ivermectin.

So I will go out on a limb and say that CD5024 is Topical Ivermectin 1%. Good news – rosacea sufferers might shortly have a new treatment available to them.

Do Let Us Know

Please do let us know in the comments below if you can confirm CD5024 is Ivermectin based, or if you get to be involved in the trials, how it goes.

Related Articles

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Taro Pharmaceuticals in fact already markets a generic form of Metrogel – Metronidazole Gel USP, 0.75%

When the patent covering Metrogel 0.75% expired, Galderma changed the formulation, increased the concentration of metronidazole to 1% and now produces the best-known rosacea treatment, Metrogel 1%.

This is good news for rosacea suffers, who can only benefit from competition in the rosacea treatment staples market. Often rosacea sufferers come away from their first visit to the doctor and pharmacist with one thought – Why is this Metrogel so expensive?

Trial CT01513863 is listed to compare Taro Pharmaceutical’s Generic Metronidazole 1% Gel with Galderma’s Metrogel 1% (and also placebo).

Clinical Trial NCT01513863

A Therapeutic Equivalence Study of Two Metronidazole 1%Topical Gel Treatments for Patients With Rosacea (MTZG)

A Randomized, Double-Blind, Placebo Controlled, Parallel Design, Multi-Site Clinical Study to Compare the Bioequivalence of Two Metronidazole 1% Topical Gel Formulations in Patients With Moderate to Severe Rosacea

Arm 1

Metronidazole Topical Gel 1%: Experimental

Intervention: Drug: Metronidazole Topical Gel 1%

Arm 2

Metronidazole Topical Gel 1% (Metrogel ): Active Comparator

Intervention: Drug: Metronidazole Topical Gel 1% (Metrogel)

Arm 3

Placebo: Placebo Comparator

Intervention: Drug: Placebo

Related Articles

• Generic Metrogel soon – Fougera
• Metrogel 1% Pump; for those who don’t like a Tube?
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Do We Need Finacea Foam?

It seems clear the Intendis wants to expand the number of products it manufactures to treat rosacea. This makes sense from the point of view of the company; another potential revenue stream and more products appear in your portfolio.

But what about rosacea sufferers – should they be excited about Finacea Foam? Well that is yet to be seen. It seems unlikely to me that a mineral oil based emulsion, such as is common in foaming products, will offer too many options to wanting rosacea sufferers. Time will tell.

Investigational Azelaic Acid Foam Quells Rosacea

11/17/11

FROM THE ANNUAL CONGRESS OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY

Medical Dermatology

By: BRUCE JANCIN, Skin & Allergy News Digital Network

LISBON – Physicians may soon have a new option for the treatment of papulopustular rosacea in the form of 15% azelaic acid foam.

The 15% foam is an extension of an existing product line which includes 15% azelaic acid gel as an approved topical therapy for mild to moderate rosacea, Dr. Blanka Havlickova explained at the annual congress of the European Academy of Dermatology and Venereology.

VITALS

Major Finding: In all, 43% of patients with papulopustular rosacea were rated as clear or as having minimal residual disease after 12 weeks of twice-daily, topical, 15% azelaic acid foam therapy.

Data Source: A double-blind, vehicle-controlled, randomized clinical trial of 401 patients with mild to moderate papulopustular rosacea who were randomized to 12 weeks of twice-daily, self-applied azelaic acid foam or vehicle.

Disclosures: The trial was funded by Intendis, which is developing the investigational agent.

Related Articles

• Finacea Foam vs. Finacea Gel
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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.

Related Articles

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

Recently a Cochrane review of 58 clinical trials told us that Metrogel, Finacea and Oracea are Best for Rosacea.

What is a Cochrane Review?

From The Cochrane Collaboration: Cochrane Reviews are designed to facilitate the choices that doctors, patients, policy makers and others face in health care. Most Cochrane Reviews are based on randomized controlled trials, but other types of evidence may also be taken into account, if appropriate.

Powell’s Comments

Interventions for ‘rosacea’

F.C. Powell, S. Ni Raghallaigh, British Journal of Dermatology, Volume 165, Issue 4, pages 707–708, October 2011

[speaking of Cochran Reviews] Reviews such as these are important summaries of evidence relating to the efficacy of particular treatments. They also reinforce the need for high-quality RCTs for future research. However, dermatologists should be aware that this review has limitations for clinical practice for two main reasons.

[read more]

Professor Powell suggests 3 reasons that large clinical trials are only part of the story. Here is my paraphrasing.

• Firstly, clinical trials almost always only interested in treating the papules and pustules of rosacea.
• Secondly, it is also worth noting that because large clinical trials are so expensive, only big pharmaceuticals companies will fund them. This leads to a bias where cheap traditional treatments are unlikely to be explored. It makes perfect sense that pharmaceutical companies want to research and develop new products that will lead to profits for their shareholders.
• Thirdly only concentrating on large trials will inhibit experimentation by dermatologists that drive the innovation we see in the “short form report” journal article.

As much I really want to see new treatments proven effective by a randomized trial, I do appreciate that this approach really is too restrictive. None of us want to visit the doctor and only have them offer the same old treatments, especially if they have already been found wanting.

Dermatologists that are willing to try innovative methods based on their knowledge – that really is something we need to encourage.

Featured Book

Related Articles

• Book Review: Rosacea: Diagnosis and Management, Frank C. Powell
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A recently posted proposed Clinical Trial has me thinking that Galderma wants to be able to market Oracea as a product to Maintain Rosacea Remission.

First Some History

In 1998, Archives of Dermatology published a much quoted paper Topical Metronidazole Maintains Remissions of Rosacea. (the PDF of the full paper is available online). The premise of the research was that for a majority of subjects studied, once rosacea symptoms (specifically their papules and pustules) were brought under control with oral tetracycline and topical metronidazole combined, the remission of symptoms could be maintained by the use of metrogel alone.

The 1998 study was funded by Galderma and the distinguished list of authors included academics and consultants paid by Galderma.

Note that Metrogel 1% was launched in the US in 2005, well after the 1998 trial that used Metrogel 0.75%, which at that stage was still protected by Galderma’s patents.

Oracea Maintains Remission?

This new trial will attempt to prove that Oracea is also capable of keeping the papules and pustules of rosacea at bay, once they have first been brought under control when treated in combination with Metrogel 1%.

The trial will also be able to confirm the safety of Oracea when used for a period of up to 1 year. Which pharmaceutical company wouldn’t want to be able to promote their profitable drug as effective and safe for such a long period?

Should this trial succeed Galderma will be able to market Oracea in new ways in the future.

Clinical Trial NCT01426269

Evaluation of Relapse, Efficacy and Safety of Long-term Treatment With Oracea vs Placebo After 12 Weeks of Oracea and MetroGel 1%

The purpose of this study is to assess relapse, efficacy and safety in subjects with rosacea during long-term treatment with either Oracea® or placebo, after an initial 12-week regimen of Oracea® and MetroGel® 1%.

Detailed Description:

Adult subjects with moderate to severe papulopustular rosacea will receive Oracea and MetroGel 1% once daily during phase 1 (baseline to week 12) of the study.

Subjects will be eligible to enter phase 2 of the study based upon improvements in the Investigator’s Global Assessment (IGA) score.

During phase 2, subjects will receive either Oracea or placebo once daily for up to an additional 40 weeks. Subjects who relapse during phase 2 will be discontinued from the study.

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