Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: two phase 3, multicenter, randomized, double-blind, placebo-controlled studies.

BACKGROUND: Imiquimod 3.75% and 2.5% creams were studied for the treatment of actinic keratosis (AK) of the full face or balding scalp, to determine comparable efficacy and tolerability to imiquimod 5% cream. METHODS: In two identical multicenter, randomized, double-blind, placebo controlled studies. Adult subjects with 5 to 20 visible lesions, or palpable AKs in an area that exceeded 25 cm² on either the face or balding scalp were randomized to imiquimod 3.75%, 2.5% or vehicle cream (1:1:1) applied once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed 8 weeks posttreatment (End of Study Visit [EOS]). Primary efficacy was rate of complete clearance of AK lesions. Secondary efficacy endpoints were rate of partial clearance at EOS (≥ 75% reduction in number of AK lesions compared to baseline) and median percent decrease from baseline lesion count. Safety assessments included visual assessment of local skin reactions (LSRs), number and duration of study treatment rest periods required due to intolerant LSRs, adverse events (AEs) and clinical laboratory tests. RESULTS: Overall 479 patients were randomized to imiquimod 3.75%, 2.5%, or vehicle. Complete clearance rates were 35.6%, 30.6%, and 6.3% respectively (both P<.001 versus vehicle). The difference in complete clearance rates (imiquimod minus vehicle) was 29.3% and 24.3%, respectively. Partial clearance rates were 59.4%, 48.1%, and 22.6% respectively (both P<.001 versus vehicle). Median % reductions in AK lesions were 81.8%, 71.8%, and 25.0% respectively (P<.001 versus vehicle). All primary and secondary efficacy endpoints were greater in Study 1. Photodamage in the treatment area was 'much improved' with imiquimod 3.75%. Both active creams were well tolerated with few treatment-related discontinuations. CONCLUSIONS: In two well-controlled Phase 3 studies, both imiquimod 3.75% and 2.5% creams were more effective than vehicle and well tolerated when administered daily as a 2-week on/off/on regimen to treat AK. Reduction in AK lesions was comparable to that reported with imiquimod 5% with fewer local AEs.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: two phase 3 multicenter, randomized, double-blind, placebo-controlled studies.

BACKGROUND: Imiquimod 3.75% and 2.5% creams were studied for the treatment of actinic keratosis (AK) of the full face or balding scalp, to determine comparable efficacy and tolerability to imiquimod 5% cream. METHODS: In two identical multicenter, randomized, double-blind, placebo controlled studies. Adult subjects with 5 to 20 visible lesions, or palpable AKs in an area that exceeded 25 cm² on either the face or balding scalp were randomized to imiquimod 3.75%, 2.5% or vehicle cream (1:1:1) applied once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed 8 weeks posttreatment (End of Study Visit [EOS]). Primary efficacy was rate of complete clearance of AK lesions. Secondary efficacy endpoints were rate of partial clearance at EOS (≥ 75% reduction in number of AK lesions compared to baseline) and median percent decrease from baseline lesion count. Safety assessments included visual assessment of local skin reactions (LSRs), number and duration of study treatment rest periods required due to intolerant LSRs, adverse events (AEs) and clinical laboratory tests. RESULTS: Overall 479 patients were randomized to imiquimod 3.75%, 2.5%, or vehicle. Complete clearance rates were 35.6%, 30.6%, and 6.3% respectively (both P<.001 versus vehicle). The difference in complete clearance rates (imiquimod minus vehicle) was 29.3% and 24.3%, respectively. Partial clearance rates were 59.4%, 48.1%, and 22.6% respectively (both P<.001 versus vehicle). Median % reductions in AK lesions were 81.8%, 71.8%, and 25.0% respectively (-<.001 versus vehicle). All primary and secondary efficacy endpoints were greater in Study 1. Photodamage in the treatment area was 'much improved' with imiquimod 3.75%. Both active creams were well tolerated with few treatment-related discontinuations. CONCLUSIONS: In two well-controlled Phase 3 studies, both imiquimod 3.75% and 2.5% creams were more effective than vehicle and well tolerated when administered daily as a 2-week on/off/on regimen to treat AK. Reduction in AK lesions was comparable to that reported with imiquimod 5% with fewer local AEs.

Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl.

AIM: To investigate the relationship between effective fentanyl sublingual spray (FSS) doses for breakthrough cancer pain (BTCP) and around-the-clock (ATC) transdermal fentanyl patch (TFP). METHODS: Adults tolerating ATC opioids received open-label FSS for 26 days, followed by a 26-day double-blind phase for patients achieving an effective dose (100-1600 µg). RESULTS: Out of 50 patients on ATC TFP at baseline, 32 (64%) achieved an effective dose. FSS effective dose moderately correlated with mean TFP dose (r = 0.4; p = 0.03). Patient satisfaction increased during the study. Common adverse event included nausea (9%) and peripheral edema (9%). CONCLUSION: FSS can be safely titrated to an effective dose for BTCP in patients receiving ATC TFP as chronic cancer pain medication. ClinicalTrials.gov identifier: NCT00538850.