High doses of sublingual tablets of house dust mite allergen extracts: Lung function assessment in a phase I study in adults with mite-associated allergic asthma

Rationale: The safety and tolerability of sublingual tablets of house dust mite (HDM) allergen extracts at doses up to 2000IR in subjects with HDM-associated allergic asthma have been previously reported. Here we present the impact of short term treatment on lung function. Methods: Adults with HDM-associated allergic asthma controlled with therapies consistent with GINA treatment Step 2, 3 or 4 were enrolled in this double-blind placebo-controlled Phase I study. Six dose-regimens with progressive incremental dosing from 300IR to 2000IR were studied sequentially. Within each dose-regimen group, subjects were randomised 3:1 to receive either HDM tablets or placebo for 10 consecutive days. Spirometry was performed daily pre- and post-dose administration. Results: 94 subjects were randomised and received either 300IR (n=11), 500IR (n=12), 800IR (n=12), 1000IR (n=12), 1500IR (n=12), 2000IR (n=12) or Placebo (n=23). One actively treated subject (1500IR) experienced a decrease in FEV 1 value of at least 20% compared to the pre-dose assessment during the treatment period. This change in FEV 1 was not associated with any respiratory symptoms or any adverse event. One placebo-recipient experienced two decreases of at least 20% including one associated with bronchospasm. All variations in FEV 1 were transient and did not recur on the subsequent days of treatment. Conclusion: In this safety study, sublingual tablets of HDM allergen extracts administered at doses up to 2000IR in subjects with HDM-associated allergic asthma did not negatively impact the lung function.