Iodixanol nasal solution reduces allergic rhinoconjunctivitis signs and symptoms in Allergen BioCube®: a randomized clinical trial

Abstract

Purpose: Allergic rhinitis (AR) affects ~20% of the population worldwide. The objectives of this study were to evaluate the safety and efficacy of iodixanol nasal solution (Nasapaque) for AR treatment, using the Allergen BioCube® (ABC®), an environmental exposure unit. Iodixanol is a commonly used contrast media agent that shows efficacy on the signs and symptoms of AR.

Patients and methods: Seventy-three adult subjects with AR were randomized to iodixanol or placebo treatment in a double-masked efficacy and safety study conducted outside of ragweed pollen season. In-office treatment was administered after BioCube® ragweed pollen exposure, and again 8 days later prior to ragweed exposure. Nasal and ocular efficacy and safety assessments were conducted before and after treatment.

Results: Iodixanol treatment resulted in statistically significantly lower total nasal symptom scores as compared to placebo at several time points post-treatment and ABC exposure. Individual nasal and ocular symptoms, notably nasal itching and ocular itching, showed evidence of lower scores in the iodixanol group. Peak nasal inspiratory flow (PNIF) improved (9%-16%) with iodixanol from baseline as compared to PNIF in the placebo group which ranged from 3% worsening to improvement of 2%. Few (9) adverse events occurred.

Conclusion: Iodixanol nasal solution demonstrated efficacy for relief of several nasal and ocular allergic rhinoconjunctivitis signs and symptoms, and was safe and well tolerated in this early Phase II exploratory trial. Further studies with iodixanol are warranted. Allergy challenge models such as the ABC provide valuable assessments of allergen exposures and drug efficacies.

Study identification number: NCT02377895.

Keywords: allergic rhinitis; allergy; contrast media agent; environmental exposure unit.

Figures

Figure 1

Study design. Notes: During the five study visits, evaluations and treatments proceeded as follows: Visit 1: (day −15 to −3): screening procedures at visit 1 determined subject eligibility. Visit 2: (day −3 to −2): subject ragweed priming. Visit 3: (day −2 to −1): subject ragweed priming. Visit 4 (day 1): subjects exposed to ragweed pollen priming for up to 90 minutes prior to enrollment qualification review. Subjects were enrolled and randomized if they met the inclusion/exclusion criteria and had a positive challenge response at the 90 minutes time point of ABC exposure, defined as TNSS ≥6. Relief study treatment (250 µL/nostril, odorless to maintain mask with placebo) or placebo was administered, followed by 7.5 hours of BioCube allergen exposure and assessment. Visit 5 (day 8): subjects were treated prophylactically with study treatment. Abbreviations: ABC, Allergen BioCube®; TNSS, total nasal symptom score.

Figure 2

Consort diagram. Abbreviation: PEFR peak expiratory flow rate.

Figure 3

TNSS change from pre- to post-treatment (visit 4, day 1). Notes: Evidence of an effect of iodixanol for mean TNSS was seen as early as 20 minutes (P=0.01), with efficacy as late as 3 hours (P=0.03). Abbreviation: TNSS, total nasal symptom score.

Figure 4

Change in nasal itching from pre- to post-treatment (visit 4, day 1). Notes: Evidence of an effect of iodixanol for mean nasal itching was seen as early as 15 minutes (P=0.03), with efficacy as late as 4 hours 30 minutes (P=0.04).

Figure 5

Change in ocular itching from pre- to post-treatment (visit 4, day 1). Notes: Evidence of an effect of iodixanol for mean ocular itching occurred as early as 10 minutes (P=0.05), with efficacy as late as 5 hours (P=0.04).