Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a phase-1 study.
BACKGROUND: A single-centre, randomized, double-blind, placebo-controlled study. AIMS: To compare the safety and tolerability of four different sublingual immunotherapy (SLIT) regimes in grass pollen allergic rhinitis. METHODS: Thirty subjects sensitized to grass pollen were enrolled and allocated to four groups. Sublingual immunotherapy was administered in tablets daily for 10 days. Groups 1 and 2 received incremental sublingual doses of 100, 200, 300, 400 and 500 IR, Group 1 daily and Group 2 increments every second day. Repeated constant dose regimens of 300 IR and 500 IR were administered in Groups 3 and 4 respectively. Safety assessments included adverse events (AE), vital signs, electrocardiogram (ECG) and clinical laboratory tests. RESULTS: Sublingual immunotherapy 300 IR (Group 3) administered in a constant dose and incremental doses up to 500 IR (Groups 1 and 2) were generally well tolerated. The majority of AEs were mild to moderate, the most common being oral pruritus, throat irritation and swollen tongue. Severe local AEs (swelling of throat) were observed only for Group 4. No serious systemic AEs were reported. There were no relevant changes in clinical laboratory, vital signs and ECG data. CONCLUSION: Adverse events were mostly local (sublingual), were not severe and resolved rapidly. Using a 5-day induction regimen high-dose treatment up to 500 IR could be administered without important side-effects, in contrast to initiating with a constant dose of 500 IR. The data indicate that a short dose increase phase may reduce the incidence of AEs when high-dose SLIT is administered.