Secondary Endpoints
The percent of subjects achieving clear or almost clear based on the IGA rating and percent reduction of inflammatory lesions at week 4 and at week 8 are the secondary endpoints.
Lesion Counts (Papules/Pustules)
Counting of the number of papules/pustules at each study visit was completed by the investigator using only the face in the assessment (the whole face down from the hairline edge to the mandibular line).
Subject Global Assessment (SGA)
The Subject Global Assessment (SGA) was rated by all randomized subjects at each study visit using a 5-point comparative grading system (much worse, slightly worse, same, slightly better, much better).
Study Compliance
Compliance with the study treatment regimen was assessed at each visit by study site personnel. If the total amount of study medication used was less than half of the quantity of dispensed drug, those subjects were excluded from statistical analysis.
SAFETY AND TOLERABILITY EVALUATIONS
Local Signs and Symptoms (Facial Skin)
At each visit, the current severity of erythema, dryness, peeling, and oiliness using a 5-point scale for each parameter was rated as defined in the study protocol (0=absent, 1=trace, 2=mild, 3=moderate, 4=severe). The current severity of pruritus was documented from the subject through questioning by the investigator at each visit using a 6-point scale as defined in the study protocol (0=absent, 1=trace, 2=mild, 3=moderate, 4=marked, 5=severe).
Adverse Events
All subjects were monitored throughout the study for adverse events (AEs), irrespective of causality, including any illness, injury, toxicity, sensitivity, or sudden death. A reported AE must either not be present pre-study or must worsen in either intensity or frequency during the study. An unexpected AE was defined as any treatment-related AE that is not identified in nature, severity, or frequency in current literature as related to the study medication. Any serious or treatment-related unexpected AEs occurring during the study were promptly reported to the IRB as per protocol-mandated study guidelines.
Statistical Analysis
An estimated total of 100 subjects was the target sample size for this pilot study.
Statistical analyses were conducted on an intent-to-treat basis, with all tests two-sided and interpreted at a 5% significance level. Descriptive statistics (ie, mean, standard deviation, etc.) were provided for all continuous variables and frequencies and for all categorical variables, presented by treatment group. Comparisons between treatment groups will be performed using an ANCOVA technique; baseline values were used as the covariate providing necessary assumptions for parametric test satisfaction. The Wilcoxon Rank-Sum test was used if needed assumptions for parametric testing were not satisfied; comparative mean scores were also evaluated. Safety analyses were performed assessing incidence and severity of local tolerance signs and symptoms and adverse and/or unexpected events, including comparisons of mean scores. A complete listing of all reports of adverse and/or unexpected events was collected and tabulated.
At each visit, the current severity of erythema, dryness, peeling, and oiliness using a 5-point scale for each parameter was rated as defined in the study protocol (0=absent, 1=trace, 2=mild, 3=moderate, 4=severe). The current severity of pruritus was documented from the subject through questioning by the investigator at each visit using a 6-point scale as defined in the study protocol (0=absent, 1=trace, 2=mild, 3=moderate, 4=marked, 5=severe).
Adverse Events
All subjects were monitored throughout the study for adverse events (AEs), irrespective of causality, including any illness, injury, toxicity, sensitivity, or sudden death. A reported AE must either not be present pre-study or must worsen in either intensity or frequency during the study. An unexpected AE was defined as any treatment-related AE that is not identified in nature, severity, or frequency in current literature as related to the study medication. Any serious or treatment-related unexpected AEs occurring during the study were promptly reported to the IRB as per protocol-mandated study guidelines.
Statistical Analysis
An estimated total of 100 subjects was the target sample size for this pilot study.
Statistical analyses were conducted on an intent-to-treat basis, with all tests two-sided and interpreted at a 5% significance level. Descriptive statistics (ie, mean, standard deviation, etc.) were provided for all continuous variables and frequencies and for all categorical variables, presented by treatment group. Comparisons between treatment groups will be performed using an ANCOVA technique; baseline values were used as the covariate providing necessary assumptions for parametric test satisfaction. The Wilcoxon Rank-Sum test was used if needed assumptions for parametric testing were not satisfied; comparative mean scores were also evaluated. Safety analyses were performed assessing incidence and severity of local tolerance signs and symptoms and adverse and/or unexpected events, including comparisons of mean scores. A complete listing of all reports of adverse and/or unexpected events was collected and tabulated.
STUDY OUTCOMES
Among the 102 subjects enrolled, 97 subjects completed the study, 72 in the sarecycline-treated group and 25 in the Centrum-treated group. Five subjects withdrew for varying reasons. All results throughout this report are based on the 97 subjects that completed the study. The majority of subjects were female (80; 82%) and white (95; 98%). The mean age was 52.4 years (SD = 14.5 years) and similar in both study groups, with an age range of 22 years to 81 years. Subjects were enrolled between 6/30/2019 through 7/1/2020, with a study period of 455 days. Times between study visits were consistent over all study sites and treatment groups.
Primary Endpoints
IGA Primary Endpoint
At baseline, IGA scores were evenly distributed between treatments at baseline (van Elteren test, P=.75). There were significant reductions in IGA scores from baseline to Week 12 for both study groups (sarecycline P<.001, Centrum P=.0008), with the sarecycline group exhibiting greater reductions (P<.0001). With regard to achieving clear or almost clear at week 12, sarecycline performed significantly better than Centrum (P<.0001), with 75 percent of sarecycline-treated subjects IGArated as clear or almost clear by EOS compared to 16 percent of Centrum-treated subjects. Data for the IGA primary endpoint are depicted in Table 2. The percentage of subjects reaching the IGA primary endpoint was 75 percent (54/72 subjects) in the sarecycline group compared to 16 percent (4/25 subjects) in the Centrum group.
Primary Endpoints
IGA Primary Endpoint
At baseline, IGA scores were evenly distributed between treatments at baseline (van Elteren test, P=.75). There were significant reductions in IGA scores from baseline to Week 12 for both study groups (sarecycline P<.001, Centrum P=.0008), with the sarecycline group exhibiting greater reductions (P<.0001). With regard to achieving clear or almost clear at week 12, sarecycline performed significantly better than Centrum (P<.0001), with 75 percent of sarecycline-treated subjects IGArated as clear or almost clear by EOS compared to 16 percent of Centrum-treated subjects. Data for the IGA primary endpoint are depicted in Table 2. The percentage of subjects reaching the IGA primary endpoint was 75 percent (54/72 subjects) in the sarecycline group compared to 16 percent (4/25 subjects) in the Centrum group.
