AEs in the first 3 months of the study (41%; 202/498), while 20% (86/427) of subjects reported AEs in months 3 to <6; 22% (82/380) in months 6 to <9, and 17% (58/341) in months 9 to <12. AEs reported by >1% of subjects are shown in Table 2. Severe AEs were experienced
by 8% (38/498) of subjects; those occurring in more than one subject included application-site irritation (3 subjects), headache (3 subjects), back pain (2 subjects), depression (2 subjects), pneumonia
(2 subjects), and seborrheic dermatitis (2 subjects). Of these, only application-site irritation was considered to be related to the study product. No individual AE was reported by >8% of subjects, and most were unrelated to the study product. Treatment-related AEs were reported by 14% (70/498) of subjects; those reported by ≥1% of subjects included application-site irritation (8%; 38/498), application-site pain (4%; 19/498), application-site pruritus (1%; 6/498), and increased alanine aminotransferase (ALT; 1%; 3/498).
A total of 21 serious AEs (SAEs) were reported for 17 subjects; 1 subject had an AE of hepatitis C (no treatment received), which, in the study sponsor’s opinion, was serious, although it was later downgraded by the investigator to nonserious; 1 subject died of lung cancer. None of the SAEs were considered to be related
to the study product or, with the exception of the subject who died, resulted in discontinuation from the study.
Nine subjects discontinued use of the study product because of AEs; 7 due to nonserious treatment-related AEs, 5 of which were related to application-site irritation and/or pain; 2 due to nonserious
AEs that were not related to the study product, and 1 of which required the use of an excluded medication (Figure 1).
Clinical Laboratory Results
Overall, there were few changes in clinical laboratory results observed over the course of the study, and no new safety signals or trends were observed in association with any of the mean changes in hematology or chemistry values. Treatment-related AEs associated with clinical laboratory abnormalities included increased ALT (3 subjects; 1%), increased aspartate aminotransferase (2 subjects; <1%) and increased total protein (1 subject; <1%). Minor variations were observed in the proportions of subjects with high, normal, and low clinical laboratory values at each study visit relative to baseline. Abnormalities in clinical laboratory results were infrequent, and while clinically relevant increases were observed at a small number of visits, they were generally transient and did not suggest any trend.
Overall, there were few changes in clinical laboratory results observed over the course of the study, and no new safety signals or trends were observed in association with any of the mean changes in hematology or chemistry values. Treatment-related AEs associated with clinical laboratory abnormalities included increased ALT (3 subjects; 1%), increased aspartate aminotransferase (2 subjects; <1%) and increased total protein (1 subject; <1%). Minor variations were observed in the proportions of subjects with high, normal, and low clinical laboratory values at each study visit relative to baseline. Abnormalities in clinical laboratory results were infrequent, and while clinically relevant increases were observed at a small number of visits, they were generally transient and did not suggest any trend.
Vital Signs Measurements and Physical Examination Findings
No clinically meaningful changes from baseline in temperature, sitting blood pressure, or pulse rate were observed. Changes in vital signs were reported as AEs in 12 subjects; however, none were considered to be related to the study product. No clinically significant changes from baseline or abnormal physical examination findings were reported as AEs.
No clinically meaningful changes from baseline in temperature, sitting blood pressure, or pulse rate were observed. Changes in vital signs were reported as AEs in 12 subjects; however, none were considered to be related to the study product. No clinically significant changes from baseline or abnormal physical examination findings were reported as AEs.
Efficacy Assessments
On average, target lesions had moderate erythema, scaling, and pruritus at baseline (Table 3). A 2-unit improvement from baseline
in mean (standard deviation [SD]) severity was recorded for target lesion erythema, scaling, and pruritus (baseline scores: 3 [0.59] units, 3 [0.6] units, and 3 [0.9] units, respectively) at week 4, and maintained thereafter at weeks 8, 16, 26, 39, and 52 (or ET). Target lesions had faint erythema, minimal scaling, and minimal pruritus at all postbaseline study visits. A 1-unit improvement from baseline in mean [SD] ISGA score (baseline score: 3 [0.57]) for the target lesion was observed at week 4, followed by a 2-unit improvement at week 8, which was maintained at weeks 16, 26, 39, and 52 (or ET).
The poststudy questionnaire on patient preferences showed that approximately two-thirds of patients preferred a foam to other forms of vehicle used previously for seborrheic dermatitis (Table 4a). A similar score was obtained for the overall preference
of the foam vehicle (Table 4b).
DISCUSSION
The primary objective of this study was to evaluate the long-term safety of ketoconazole foam, 2%, used twice daily in the treatment of seborrheic dermatitis in immunocompetent subjects
12 years and older. Following evaluation of all reported
