Randomized study of the efficacy, safety, and pharmacokinetics of SPR720 for the treatment of Mycobacterium avium complex pulmonary disease
摘要
SPR720 is an aminobenzimidazole that is converted rapidly in vivo to the active moiety SPR719, which inhibits in mycobacteria the ATPase activity of DNA gyrase B. The efficacy, safety, and pharmacokinetics of orally administered SPR720 were evaluated in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). Twenty-two patients meeting criteria for nodular-bronchiectatic NTM-PD were randomly assigned in a 1:1:1 ratio to placebo, SPR720 500 mg once daily (QD), or SPR720 1000 mg QD for 56 days, and three patients received open-label treatment with SPR720 1000 mg QD or SPR720 500 mg twice daily. For the primary efficacy endpoints, observed weekly sputum log10 CFU/mL and time to positivity, no difference was observed among treatment groups with no dose response between SPR720 500 mg QD and 1000 mg QD. Mycobacterial suppression was maintained through Day 56. Treatment-emergent adverse events were reported in six (75%), seven (100%), and nine (90%) patients with placebo, SPR720 500 mg QD, and SPR720 1000 mg, respectively. Dose-dependent, reversible hepatic enzyme elevations occurred in 11 (65%) patients treated with SPR720, including three (18%) who experienced grade 3 toxicity. Orally administered SPR720 had limited bacteriostatic activity against Mycobacterium avium complex and caused reversible hepatic enzyme elevations in the majority of patients.
This study was registered with ClinicalTrials.gov: NCT05496374, 09/08/2022.