Azelaic acid gel was evaluated for the treatment of mild to moderate papulopustular rosacea in two multicenter, randomized, double-blind, vehicle-controlled, 12-week clinical trials having identical protocols and involving a total of 664 (active: 333; vehicle: 331) subjects aged 21 to 86 years (mean age = 49). Overall, 92.5% of subjects were Caucasian and 73% of subjects were female. Enrolled subjects had mild to moderate rosacea with a mean lesion count of 18 (range 8 to 60) inflammatory papules and pustules. The following subjects were excluded: a) those without papules and pustules; b) those with nodules, rhinophyma, or ocular involvement and c) those with a history of hypersensitivity to propylene glycol or to any other ingredients of the study drug. Azelaic acid gel or its vehicle were to be applied twice daily for 12 weeks; no other topical or systemic medication affecting the course of rosacea and/or evaluability was to be used during the studies. Subjects were instructed to avoid spicy foods, thermally hot food/drink and alcoholic beverages during the study. Subjects were also instructed to use only very mild soaps or soapless cleansing lotion for facial cleansing.
The primary efficacy endpoints included both 1) change from baseline in inflammatory lesion counts as well as 2) success defined as a score of clear or minimal with at least a 2-step reduction from baseline on the Investigator s Global Assessment (IGA), defined as follows below:
CLEAR:No papules and/or pustules; no or residual erythema; no or mild to moderate telangiectasiaMINIMAL:Rare papules and/or pustules; residual to mild erythema; mild to moderate telangiectasiaMILD:Few papules and/or pustules; mild erythema; mild to moderate telangiectasiaMILD TO MODERATE:Distinct number of papules and/or pustules; mild to moderate erythema; mild to moderate telangiectasiaMODERATE:Pronounced number of papules and/or pustules; moderate erythema; mild to moderate telangiectasiaMODERATE TO SEVERE:Many papules and/or pustules, occasionally with large inflamed lesions; moderate erythema; moderate degree of telangiectasiaSEVERE:Numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate or severe erythema; moderate or severe telangiectasia
Primary efficacy assessment was based on the intent-to-treat (ITT) population with the last observation carried forward (LOCF).
Both trials demonstrated a statistically significant difference in favor of azelaic acid gel over its vehicle in both reducing the number of inflammatory papules and pustules associated with rosacea (Table 2) as well as demonstrating success on the IGA in the ITT-LOCF population at the end of treatment.
Table 2: Inflammatory Papules and Pustules (ITT population)*
| Study One Azelaic Acid Gel, 15% N=164 | Study One VEHICLE N=165 | Study Two Azelaic Acid Gel, 15% N=167 | Study Two VEHICLE N=166 |
| Mean Lesion Count Baseline | 17.5 | 17.6 | 17.9 | 18.5 |
End of Treatment* | 6.8 | 10.5 | 9.0 | 12.1 |
Mean Percent Reduction End of Treatment* | 57.9% | 39.9% | 50.0% | 38.2% |
*ITT population with last observation carried forward (LOCF)
Although some reduction of erythema which was present in subjects with papules and pustules of rosacea occurred in clinical trials, efficacy for treatment of erythema in rosacea in the absence of papules and pustules has not been evaluated.
Azelaic acid gel was superior to the vehicle with regard to success based on the IGA of rosacea on a 7-point static score at the end of treatment (ITT population; Table 3).
Table 3: Investigator s Global Assessment at the End of Treatment*
| Study One Azelaic Acid Gel, 15% N=164 | Study One VEHICLE N=165 | Study Two Azelaic Acid gel, 15% N=167 | Study Two VEHICLE N=166 |
| Clear, Minimal or Mild at End of Treatment (% of Subjects) | 61% | 40% | 61% | 48% |
*ITT population with last observation carried forward (LOCF)
