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?
• Metronidazole (Metrogel, Flagyl) is a popular rosacea treatment

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
• Finacea Foam being trialled
• Finacea Gel (azelaic acid 15%) as a Rosacea Treatment

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
• General Rosacea Research Methods Still Wanting 
• Metrogel, Finacea and Oracea are Best for Rosacea

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.

Related Articles

• Oracea to replace Periostat, new rosacea treatment launched
• How Collagenex (Galderma) are Promoting Oracea
• Oracea Phase IV Results (ORCA) show users are happy
• Oracea too expensive ?
• Oracea set to generate $260m in 2011

The trial is scheduled to involve 170 participants at multiple centres. If you are able to attend the Los Angeles clinic as detailed below, you will be compensated and may even end up receiving free Oracea during the trial.

From Pearl E Grimes, M.D. Clinical Trials

Do you suffer from Rosacea?

Dr. Pearl E. Grimes, Medical Director of the Vitiligo & Pigmentation Institute of Southern California, is nationally and internationally recognized for her research work. The institute is conducting a clinical study for rosacea.

If you are between the ages of 18 and 70 and have a red face with at least 5 but no more than 40 papules and/or pustules, you may be eligible to participate in this study. Involvement in this study may last up to 13 weeks.

All qualified participants will receive all study-related care and either oral medication or placebo at no cost, and will be compensated for time, participation and travel.

Are you interested?

If you are interested, please contact:
Kali Ghazali, CRC
Vitiligo & Pigmentation Institute of Southern California
5670 Wilshire Blvd, Suite 650
Los Angeles, CA 90036
t: (323) 467-4389 ext 6
e: Research@pearlgrimesmd.com

Related Articles

• Generic Oracea Legal Trial now in July 2011
• Galderma, with Oracea looking for Inflammatory Pathway Markers
• Cutis posts Oracea Phase 4 (ORCA) papers for free online
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Now a new trial has been listed to compare Finacea Gel with Finacea Foam.

As I noted a year ago, these kind of `swings and roundabouts’ trials tend to be seen when a product reaches maturity and the manufacturer is seeking to build their portfolio with derivative products.

This trial will be valuable because it will be able to prove if the foam delivery system is able to offer a measurable benefit to users. Note that this trial will be looking at the Pharmacokinetics of the active ingredient – azelaic acid; that is, how much of it is available in the skin for the 12 hours after application. Thus the trial will be able to provide proof that the foam delivery mechanism it more or less effective or indeed just as effective as the topical gel.

The purpose of the test also refers to “repeated application” but doesn’t detail what this means.

Safety and Pharmacokinetics of Azelaic Acid Foam, 15% in Papulopustular Rosacea

Investigator-blinded, Randomized, Cross-over, Multiple Dose Phase I Study on Safety and Pharmacokinetics of Topically Applied Azelaic Acid Foam, 15% Compared to Azelaic Acid Gel, 15% in Subjects With Papulopustular Rosacea.

Primary Outcome Measures:

• Baseline corrected area under the curve (AUC) [ Time Frame: 12 hours ]

Related Articles

• Finacea Foam being trialled for rosacea
• Finacea (azelaic acid 15%) as a Rosacea Treatment

Timolol has been used orally in the treatment for hypertension and opthalmic solutions have been used to reduce intraocular pressure in glaucoma.

Clinical Trial NCT01250457: Topical Timolol for the Treatment of Benign Vascular Periocular Lesions

Pre-treatment and post-treatment lesion size will then be compared to determine whether twice-daily topical application of timolol 0.5% solution alters the morphometry of benign vascular periocular lesions.

…

Benign vascular tumors of the eyelid are common causes of ocular morbidity. Capillary hemangiomas in children cause refractive and occlusive amblyopia. In adults, Rosacea-associated eyelid telangiectasis and sclerosis can result in keratitis and corneal neovascularization.

Corticosteroid therapy of benign vascular lesions risks sight-threatening complications including central retinal artery occlusion and significant systemic morbidity.

Alternatively, oral and intravenous beta-blockers have been reported to induce regression of benign vascular lesions. One recent report documented efficacy of topical timolol in treating a large capillary hemangioma of the eyelid in a child.

Topical application reduces systemic side effects of beta-blockers including bradycardia, hypotension, heart block, and bronchospasm. This one-year prospective case-control series will investigate whether topical Timolol 0.5% solution applied twice daily causes significant regression of benign vascular periocular lesions.

Related Articles

• Treating Ocular Rosacea (from the AAO)
• Restasis (cyclosporine) as ocular rosacea treatment
• ocular rosacea treatment and pathogenesis
• RSRP: Beta-Blockers & Alpha Antagonists
• Sansrosa’s Sister to enter redness race
• Sansrosa started as eye drops ?

 

Phase IV trials typically try to replicate the success and safety of drugs seen in Phase III trials, but on a much larger scale. Phase IV trials are conducted after a drug is already generally available.

The ORCA study was able to confirm that the majority of sufferers of the papules and pustules of rosacea were clear or near-clear after 12 weeks of being on Oracea. The redness associated with the rosacea lesions was also similarly reduced after 12 weeks.

GALDERMA ANNOUNCES RESULTS OF LARGEST-EVER ROSACEA TRIAL

Community Based Trial Studying Oracea (OR-AY-SHA) was Designed to Reflect Real World Conditions when Managing Papulopustular Rosacea

Fort Worth, TX – October XX, 2010  (yes they really did a release with a date of XX, and released it as a Word Document whatsmore).

A community-based study of 1,421 patients with mild to severe papulopustular rosacea (PPR), found that in patients suffering from PPR, Oracea^® (doxycycline 40 mg) effectively reduces rosacea pustules and papules when used as a monotherapy treatment or when added-on to other topical rosacea therapies

…

In the monotherapy arm (Oracea prescribed on its own as a rosacea treatment), IGA (investigator global assessment) scores showed about 75% of the 826 participants were clear or near clear by week 12 while CEA (clinician erythema assessment) scores showed about 75% had no or mild erythema after 12 weeks.

Adverse events that occurred in more than 1% of the safety population included diarrhea (1.2%), nausea (1.3%), and headache (1.0%).

For background see also the Clinical Trials register entry NCT00892281;

ORCA – Oracea® for Rosacea: A Community-based Assessment

A Phase 4, Open-Label, Multicenter, Community-based, 12-Week Trial Assessment of Effectiveness, Safety, and Subject Satisfaction With Oracea® [Doxycycline, USP] Capsules 40 mg (30 mg Immediate Release & 10 mg Delayed Release Beads) When Used as Monotherapy or as Add-On Therapy to Existing Topical Regimens for the Treatment of Rosacea

Enrollment: 1421

Study Start Date: April 2009

Study Completion Date: October 2009

Primary Completion Date: October 2009

Galderma is under threat in the market for sub-antimicrobial treatments for rosacea. Mylan Pharmaceuticals is hoping to be able to manufacture Generic Oracea in the first quarter of 2011.

Related Articles

• Oracea should be tested against Generic Doxycycline
• Oracea to replace Periostat, new rosacea treatment launched

Despite the global financial economic situation and despite the seemingly crowded skincare market, the research and development of rosacea treatments continues at pace. I wonder if you would be surprised to see the number of rosacea clinical trials listed at ClinicalTrials.gov that have had activity in the last year?

Even though many products never get past official clinical trials, it is still encouraging to see that companies are still willing to invest in research and development.

1. Apremilast

This product is described as “a novel, orally available small molecule compound that exhibits anti-inflammatory activities through the suppression of multiple pro-inflammatory mediators including, TNF-alpha, interleukins 6, 17 & 23, and interferon-gamma among others.”"

It will be trialled for both Erythematotelangiectatic Rosacea and Papulopustular Rosacea (see Apremilast from Celgene being trialled for rosacea.)

2. Atralin

Atralin Gel contains Tretinoin 0.05%. Tretinoin is a topical medication that is known to improve photodamage. The study is attempting to find out if Atralin (tretinoin 0.05%) Gel used for up to 46 weeks will improve erythematotelangiectatic rosacea (ETR) (see Atralin Gel (Tretinoin 0.05%) being trialled for the redness of rosacea).

3. Calcium Dobelisate + Pulsed Dye Laser

This study is to determine the efficacy of calcium dobesilate in combination with pulsed dye laser for the treatment of rosacea. Calcium dobesilate (2,5-dihydroxybenzene sulfonate) is a drug that inhibits vascular smooth muscle cell growth and inhibits cellular proliferation (see Doxium being trialled as Pulsed Dye Laser adjunct).

4. CD07805/47 (Sansrosa)

Known previously as Sansrosa, three strengths of CD07805/47 topical gel (0.07%, 0.18%, and 0.50%) are being tested for the redness of rosacea. The study completed in December 2009 so we await the next stage of this product’s development (see Galderma sends Sansrosa backwards – Phase 2 Dosage Trials Again).

5. Finacea + Oracea vs. Metrogel + Oracea

Intendis, the makers of Finacea are sponsoring this trial. Subjects with moderate papulopustular rosacea will be treated either with azelaic acid 15% gel topically plus Oracea or with metronidazole 1% gel topically once daily plus Oracea at total of twelve weeks to determine the rapidity of improvement, and the length of time to reach 25%, 50% and 75% clearing compared to baseline (see ho hum: finacea + oracea vs. metrogel 1% + oracea).

6. Finacea Foam

A new formulation of Finacea, a foam used twice a day is being trialled. Note that they are only comparing the active against the vehicle foam, so will not be able to compare regular topical Finacea with Finacea Foam to see if the foam formulation makes any difference to the outcome (see Finacea Foam being trialled).

7. IDP-115

Dow Pharmaceutical Sciences, which is now owned by Valeant Pharmaceuticals, has completed their trials of something they call IDP-115. Whilst details are sketchy the product appears to be similar to Rosasol, a formulation of metronidazole and sunscreen agents (see Mysterious topical IDP-115 being trialled)

8. Isotretinoin (0.25 mg/kg)

This trial is looking at the medium dosage (15mg a day for a 65kg patient) of Isotretinoin in treating the papules and pustules of rosacea. (See trial NCT00882531). The company sponsoring this trial, Laboratoires Bailleul-Biorga, manufacture Oral Isotretinoin (Accutane) in strengths of 5mg, 10mg, 20mg and 40mg.

9. Minocycline Foam

A special formulation of Topical Minocycline Foam FXFM244 is being trialled in strengths of 1% and 4%. The makers of the foam, Foamix  promote the ease of application and the absence of alcohol in their products, suggesting that it is ideal for many dermatological agents (see Foamix to trial foaming topical minocycline)

10. Nycomed 0444 Gel

This Phase III trial which has listed as completed looked at Nycomed’s 0444 Gel for the treatment of the papules and pustules of rosacea. Not a lot of information has surfaced as yet as to the makeup of this product (see What is this mysterious Nycomed 0444 Gel ?).

11. Oxymetazoline (V-101)

The product is known as V-101 and all indications are that it is a formulation containing oxymetazoline (as found in products like Afrin, Vicks Sinex and Visine). V-101 is being trialled in strengths of 0.01%, 0.06%, 0.1% and 0.15% (see V-101 (Oxymetazoline) starting Dose-Finding Trials).

12. Sol-Gel SGT DER 45 EV Gel

This product know only as DER 45 EV Gel (in strengths of 1% and 5%) has been listed in a dose-range trial for the papules and pustules of rosacea. One guess is that this product is a novel form of benzoyl peroxide, but so far no more information has been published (see Sol-Gel Trialling Benzoyl Peroxide (DER 45 EV) for Rosacea).

13. SR-01

This mysterious topical, being sponsored by Dr. Mark Dahl MD from the Mayo Clinic has listed as completed. SR-01 is listed as a topical agent for the treatment of red skin (see NCT00279890).

14. Topical Oxygen (TDO)

Aria Aesthetics is sponsoring a trial where topically disolved oxygen (TDO) based cosmeceuticals are used to treat several skin conditions (see Topical Oxygen being trialled for sun damaged skin).

15. Ziana

Ziana has been approved as an acne treatment. The aim is to determine whether Clindamycin Phosphate 1.2% And Tretinoin 0.025% Gel are effective and safe in the treatment of papulopustular rosacea. (see Medicis readies to trial Ziana for rosacea)

What do you think?

Are you encouraged by the number of products in this list? Or do they feel all too much like same old same old to you?