Efficacy of Extended-Release 45 mg Oral Minocycline and Extended-Release 45 mg Oral Minocycline Plus 15% Azelaic Acid in the Treatment of Acne Rosacea

March 2013 | Volume 12 | Issue 3 | Original Article | 292 | Copyright © March 2013

J. Mark Jackson MD,a Douglas J. Lorenz PhD,b and Leon H. Kircik MDc-e

aDivision of Dermatology, bDepartment of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY cMount Sinai Medical Center, New York, NY dIndiana University School of Medicine, Indianapolis, IN ePhysicians Skin Care, PLLC, Louisville, KY

After the baseline visit, each patient was scheduled for return visits at weeks 4, 8, 12, and 16. The following evaluations were conducted at each visit: lesion score, IGA score, and CEA score.

Efficacy Evaluation

Efficacy of the study medication was assessed for each dose group compared with the placebo group on the basis of the following parameters:
Primary Efficacy Parameters
  1. Change in total inflammatory lesion count of papules plus pustules plus nodules from baseline to the week 12 visit (end point).
Secondary Efficacy Parameters
  1. Change from baseline in the IGA score to the week 12 visit (end point).
  2. Proportion of patients achieving a score of 0 or 1 (clear/near clear) on the IGA score at the week 12 visit (end point).
  3. Change in CEA score from baseline to the week 12 visit (end point).
Ancillary Efficacy Parameters
  1. Change from baseline in total lesion count (papules, pustules, and nodules) at the week 4, 8, 12, and 16 visits.
  2. Change from baseline in CEA score at the week 4, 8, 12 and 16 visits.
  3. Responder analysis: Percentage of patients achieving at least a 50% reduction from baseline inflammatory lesion count at the week 12 visit (end point).
  4. Percent change in total inflammatory lesion count from baseline to the week 12 visit (end point).

Safety Evaluation

Safety was assessed during the study by collection of study events and review of concomitant treatments. All adverse events (AEs) were recorded regardless of their intensity or relationship to the drug. Any patient who suffered a serious AE was withdrawn from the study.

Statistical Considerations

Stating the Problem
The objective of this study is to investigate the therapeutic effect of 45 mg daily oral doses of minocycline vs 45 mg daily oral doses of minocycline plus once daily 15% azelaic acid and their benefits in patients with rosacea.

Study Design

This double-blind, 2-center study was a 2-armed, parallel-group design. Treatment was randomly allocated to patients in blocks of 2. Blocks were centrally assigned to investigators as needed and based on enrollment.
The goal of the analyses was to assess evidence of an overall effect of 45 mg minocycline and the overall effect of 45 mg oral minocycline plus 15% azelaic acid in the therapy of patients with acne rosacea. Two types of study populations were analyzed, namely, the intention-to-treat (ITT) and the per-protocol (PP) populations.
Intention-to-Treat Analysis Population
The ITT population included all randomized patients for whom it could not be excluded that they had taken the study medication at least once after randomization.
The ITT population included patients who had no data at week 12 for any reason, eg, patients withdrawn from treatment before week 12. The last observations (postrandomization) in these patients were used for the ITT end point analysis reflecting each patient’s final postrandomization visit, ie, the last observation was carried forward for the end point analysis.
The analysis of safety was performed by evaluating vital signs and adverse drug experiences, based on the ITT population. The ITT analysis provides estimates of treatment effects, which may be more likely to mirror those effects observed in practice. Consequently, this analysis was considered the primary efficacy analysis.
Per-Protocol Analysis Population
The PP population is a subset of the ITT population and was defined by the absence of any major protocol violations, including violations of any inclusion/exclusion criterion.
Possible protocol violations/deviations included those defined as follows:
  • Failure to meet the inclusion criteria and pass the exclusion criteria;
  • noncompliance of treatment medication, defined as less than 80%;
  • use of concomitant drugs not allowed according to the protocol; and
  • erroneous unblinding.
  • Patients who discontinued treatment before week 12 were included in the PP analysis. However, no imputation technique to compensate for missing data was used in the PP analysis.

    Primary Efficacy Variables

    Total Inflammatory Lesion Count (Papules Plus Pustules Plus Nodules)
    Total inflammatory lesion count is the sum of the papule count, pustule count, and the nodule count. The total inflammatory lesion count obtained at week 12 (end point) was used for the primary efficacy evaluation. Any week 12 observation obtained.