Hypersensitivity incidence after sugammadex administration in healthy subjects: a randomised controlled trial.

BACKGROUND

We evaluated the incidence of hypersensitivity or anaphylaxis after repeated single-dose sugammadex administration in non-anaesthetised adults.

METHODS

In this multicentre, double-blind study (NCT02028065), healthy volunteer subjects were randomised (2:2:1 ratio) to one of three groups to receive three repeated intravenous injections of sugammadex 4 or 16 mg kg, or placebo, separated by a ∼5 week intervals. Targeted hypersensitivity assessments were performed 0.5, 4, and 24 h post-dosing, and hypersensitivity signs/symptoms were referred to a blinded independent Adjudication Committee. Anaphylaxis was determined per Sampson (Criterion 1). The primary endpoint was the proportion with confirmed hypersensitivity.

RESULTS

Of 375 evaluable subjects, 25 had confirmed hypersensitivity [sugammadex 4 mg kg: 10/151 (6.6%); sugammadex 16 mg kg: 14/148 (9.5%); placebo: 1/76 (1.3%)]. The differences in incidence rates vs placebo were 5.3% (95% confidence interval: -0.9, 10.7) for sugammadex 4 mg kg and 8.1% (1.7, 14.2) for 16 mg kg. Incidence was similar across sugammadex doses and dosing occasions, including in subjects with reactions to previous doses. Three subjects (16 mg kg group) required antihistamines/corticosteroids and discontinued the study, per protocol; symptoms resolved and no subject required epinephrine. One subject with anaphylaxis after the first 16 mg kg dose recovered completely post-treatment. There were no clinically relevant anti-sugammadex antibody or tryptase findings.

CONCLUSIONS

Hypersensitivity in response to sugammadex administration can occur in healthy subjects without history of previous sugammadex exposure. Hypersensitivity incidence was similar across sugammadex doses and numerically higher than placebo, with no evidence of sensitisation with repeated administration. Hypersensitivity is unlikely to be mediated through sugammadex-specific immunoglobulin G- or E-mediated mast cell stimulation in healthy volunteers.

CLINICAL TRIAL REGISTRATION

NCT02028065.