Cutis posts Oracea Phase 4 (ORCA) papers for free online

Written by on January 18, 2011 in doxycycline, Galderma, Oracea (40mg doxycycline) with 0 Comments


Late last year Galderma generated quite a lot of publicity in the lead up to the release of the Phase 4 trials of Oracea.

Phase IV trials typically try to replicate the efficacy 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.  Physicians typically use the Phase IV results to build confidence in prescribing a particular medicine.

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.

Now, The journal Cutis has posted the papers that describe the details of the Oracea Phase 4 trial online. You can read the full text of these papers online for free.

The supplement contains the 3 papers listed below and an introduction. Download the PDF for the full details.

The ORCA (Oracea for Rosacea: A Community-Based Assessment) Trial: A Large-Scale, Phase 4 Trial in Papulopustular Rosacea

VOL. 86 NO. 5S[i] NOVEMBER 2010

An Open-Label, Community-Based, 12-Week Assessment of the Effectiveness and Safety of Monotherapy With Doxycycline 40 mg
(30-mg Immediate-Release and 10-mg Delayed-Release Beads), Guy F. Webster, MD, PhD

Rosacea is a common inflammatory disorder of the skin of middle-aged and older adults. A unique 40-mg formulation of doxycycline (30-mg immediate-release and 10-mg delayed-release beads) developed for its anti-inflammatory properties is the only US Food and Drug Administration–approved oral medication for the disorder.
This report describes the results of the Oracea for Rosacea: A Community-Based Assessment (ORCA) trial, a phase 4 trial of the 40-mg formulation as monotherapy in adults with mild to severe papulopustular rosacea. A total of 1197 participants were enrolled in the monotherapy arm of the 12-week open-label study at 271 community-based investigational sites.

The primary outcome measure was a change in the 5-point investigator global assessment (IGA) score from baseline to end point (week 12). Secondary outcome measures included change in the 5-point clinician erythema assessment (CEA) score from baseline to end point, IGA success, and adverse events (AEs). 

The monotherapy per-protocol (PP) population was selected a priori as the primary analysis population and safety assessments were performed on all participants who received at least 1 dose of the study drug. In the PP population of 826 monotherapy participants who completed the trial, approximately 75% of participants with mild to severe rosacea at baseline were clear or near clear by week 12 according to IGA scores.

Furthermore, approximately 75% of participants had CEA scores reflecting none or mild erythema after 12 weeks. In the safety population of 1196 participants, treatment-related AEs were reported in 6.7% of participants that were mainly mild or moderate in severity.

Adverse events that occurred in more than 1% of the safety population included diarrhoea (1.2%), nausea (1.3%), and headache (1.0%). The incidence of fungal and yeast infections was 0.4%. The results of the ORCA trial support the effectiveness and safety of the 40-mg formulation of doxycycline in patients with papulopustular rosacea.

Effectiveness and Safety of Doxycycline 40 mg (30-mg Immediate-Release and 10-mg Delayed-Release Beads) Once Daily as Add-on Therapy to Existing Topical Regimens for the Treatment of Papulopustular Rosacea: Results From a Community-Based Trial, James Q. Del Rosso, DO

Rosacea is a prevalent inflammatory skin disorder that affects approximately 16 million individuals in the United States. Although its exact etiology is unknown, basic science, histologic evidence, and clinical evidence suggest that it is inflammatory in nature.

In this 12-week, open-label, multicenter, community-based, phase 4 trial, we evaluated the anti-inflammatory effects of once daily subantimicrobial-dose doxycycline 40 mg (30-mg immediate-release and 10-mg delayed release beads) in participants with papulopustular rosacea (PPR) who were receiving topical therapy (metronidazole, azelaic acid, and/or sodium sulfacetamide–sulfur) at the time of the study entry but whose rosacea symptoms were still present.

The primary outcome measure was the change in the investigator global assessment (IGA) score from baseline to end of study (week 12). Secondary outcome measures were changes from baseline to end of study in the clinician erythema assessment (CEA) score, treatment responders (IGA score of clear, near clear), and safety.
After week 12, 75.7% of participants in the per-protocol (PP) population had IGA scores of clear or near clear. In addition, there were significant differences in the distribution of baseline and week 12 IGA scores in the PP group (P=.0012). At week 12, most participants (63.6%) had mild CEA scores; the distribution was significantly different from baseline (P=.0407). Only 7% of participants had treatment-related adverse events (AEs), mostly mild or moderate in severity.

Thus the 40-mg formulation of doxycycline proved to be effective and well-tolerated in a real-world setting in participants with rosacea who were receiving topical therapy but still experiencing symptoms.

A Community-Based Study of the Effectiveness of Doxycycline 40 mg (30-mg Immediate-Release and 10-mg Delayed-Release Beads) on Quality of Life and Satisfaction With Treatment in Participants With Rosacea, Hilary E. Baldwin, MD

Changes to the skin of the face in patients with rosacea have the potential to substantially impair multiple domains of quality of life (QOL); however, the number of publications providing evidence for this topic is limited.

This 12-week, open-label, community-based, phase 4 trial of 1421 participants is the largest study of the disease to date. It explores the effects of mild to severe rosacea and its treatment on QOL.

Participants were treated with doxycycline 40 mg (30-mg immediate-release and 10-mg delayed-release beads) as monotherapy or add-on treatment to existing topical therapy.  This article examines QOL issues in the primary analysis population consisting of 966 participants who completed the trial without a major protocol violation. Quality of life was assessed at baseline and study end (week 12) with the RosaQoL , a validated 21 -question instrument.

Participant and investigator satisfaction with treatment also were evaluated. In the monotherapy group, the mean RosaQoL score was 3.3 at baseline and 2.8 at end of study. In the add-on therapy group, the mean RosaQoL score was 3.2 at baseline and 2.8 at end of study. The improvement in QOL was both clinically and statistically significant (P=.0001) and was similar in both monotherapy and add-on therapy groups.

Most participants expressed satisfaction with treatment and approximately 90% of the community-based investigators reported that they were likely or very likely to continue prescribing this formulation. The study demonstrates that the impaired QOL in patients with rosacea can be substantially improved during a 3-month period by once-daily treatment with the anti-inflammatory activity of subantimicrobial-dose doxycycline

Supported by an educational grant from Galderma Laboratories, L.P. It seems reasonable to me that because this research is funded externally to the journal, the full text of the papers can be made available for free.

The Elephant in the room

Whilst this data confirms that Oracea can continue as a mainstream rosacea treatment, the spectre of the impending availability of generic Oracea also hangs over this product’s long term profit making ability.

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About the Author: David Pascoe started the Rosacea Support Group in October 1998. .

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