Clinical Studies Experience
Because clinical trials are conducted under prescribed conditions, adverse reaction rates observed in the clinical trial may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse reactions that appear to be related to drug use for approximating rates.
The safety data presented in Table 1 (below) reflects exposure to ZIANA Gel (clindamycin phosphate, tretinoin) in 1,853 patients with acne vulgaris. Patients were 12 years and older and were treated once daily for 12 weeks. Adverse reactions that were reported in ≥1% of patients treated with ZIANA Gel (clindamycin phosphate, tretinoin) were compared to adverse reactions in patients treated with clindamycin phosphate 1.2% in vehicle gel, tretinoin 0.025% in vehicle gel, and the vehicle gel alone:
Table 1: Adverse Reactions Reported in at Least 1% of Patients
Treated with ZIANA Gel (clindamycin phosphate, tretinoin) : 12-Week Studies
|PATIENTS WITH AT LEAST ONE AR||497 (27)||342 (24)||225 (27)||91 (22)|
|Nasopharyngitis||65 (4)||64 (5)||16 (2)||5 (1)|
|Pharyngolaryngeal pain||29 (2)||18 (1)||5 (1)||7 (2)|
|Dry skin||23 (1)||7 (1)||3 (<1)||0 (0)|
|Cough||19 (1)||21 (2)||9 (1)||2 (1)|
|Sinusitis||19 (1)||19 (1)||15 (2)||4 (1)|
|Note: Formulations used in all treatment arms were in the ZIANA vehicle gel.|
Cutaneous safety and tolerance evaluations were conducted at each study visit in all of the clinical trials by assessment of erythema, scaling, itching, burning, and stinging:
Table 2: ZIANA Gel (clindamycin phosphate, tretinoin) -Treated Patients with Local Skin Reactions
|Local Reaction|| Baseline
| End of Treatment
|Erythema||636 (35)||416 (26)|
|Scaling||237 (13)||280 (17)|
|Itching||189 (10)||70 (4)|
|Burning||38 (2)||56 (4)|
|Stinging||33 (2)||27 (2)|
At each study visit, application site reactions on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe), and the mean scores were calculated for each of the local skin reactions. In Studies 1 and 2, 1277 subjects enrolled with moderate to severe acne, 854 subjects treated with ZIANA Gel (clindamycin phosphate, tretinoin) and 423 treated with vehicle. Analysis over the twelve week period demonstrated that cutaneous irritation scores for erythema, scaling, itching, burning, and stinging peaked at two weeks of therapy, and were slightly higher for the ZIANA-treated group, decreasing thereafter.
One open-label 12-month safety study for ZIANA Gel (clindamycin phosphate, tretinoin) showed a similar adverse reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.