Schering Clarinex Onset Of Action Studies Do Not Support Claim, FDA Finds
Executive Summary
Schering's four Clarinex onset-of-action studies do not support a labeling claim, FDA concluded in its review of the NDA for the antihistamine
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Schering's four Clarinex onset-of-action studies do not support a labeling claim, FDA concluded in its review of the NDA for the antihistamine. "Given the variable and inconsistent findings, any specific onset-of-action claim for labeling is difficult to support," acting team leader Badrul Chowdhury, MD/PhD, said in his medical review. The onset of action claim was one approach Schering hoped to use to differentiate Clarinex (desloratadine) from its predecessor compound Claritin (loratadine) (1 (Also see "Schering Desloratadine Onset Of Action Is 1-2 Hours - EU Review Document" - Pink Sheet, 26 Mar, 2001.), p. 13). Clarinex was approved in the U.S. Dec. 21 for the relief of nasal and non-nasal symptoms of seasonal allergic rhinitis (2 (Also see "Schering Clarinex Approval Comes In Time For Big Spring Push" - Pink Sheet, 24 Dec, 2001.), p. 34). The final approval was held up for a year by manufacturing issues (see 3 (Also see "Clarinex Approval Includes Commitments From Schering On Stability Tests" - Pink Sheet, 8 Apr, 2002.) ). Schering's four onset of action studies included a "day-in-the-park" study, two environmental exposure unit studies with grass pollen and an EEU ragweed study. The 310-subject day-in-the-park study "failed to show an onset of action at all, presumably because of large placebo response," Chowdhury said. Symptom scores decreased over the five-hour study period in both groups, with desloratadine (DCL) failing to show statistical superiority to placebo at any timepoint. "While the EEU chamber studies showed an apparent onset in the separation from placebo by 1.75 hours after a single 5 mg dose of DCL," Pulmonary-Allergy Drug Products Division Director Robert Meyer, MD, said in an Oct. 27, 2000 memo, "there appeared to be a paradoxical longer onset for a 7.5 mg dose...leading to some appropriate skepticism on behalf of the primary reviewer on the validity of these findings." One grass pollen EEU study showed onset at 1.25 hours for the 5 mg dose and 3.5 hours for the 7.5 mg dose, while the other demonstrated onset at 1.75 hours for 5 mg, the only dose studied. The ragweed pollen EEU study showed a 3-hour onset for 5 mg (2 hours without cough) and 3.5 hours for the 7.5 mg dose. [Editors' Note: The April issue of F-D-C Reports' Pharmaceutical Approvals Monthly includes more coverage of the Clarinex review. Free copies are available from Dzidra Vizbulis at 800.332.1370.] |