Early phase evaluation of SQ109 alone and in combination with rifampicin in pulmonary TB patients

摘要: OBJECTIVES: SQ109, an asymmetrical diamine, is a novel anti-TB drug candidate. This first study in patients was done to determine safety, tolerability, pharmacokinetics and bacteriological effect of different doses SQ109 alone combination with rifampicin when administered over 14 days. PATIENTS AND METHODS: Smear-positive pulmonary TB were randomized into six groups 15 receive once-daily oral treatment 75, 150 or 300 mg (10 mg/kg body weight), plus for Patients hospitalized supervised treatment, regular clinical, biochemical electrocardiographic safety assessments, pharmacokinetic profiling daily overnight sputum collection. RESULTS: safe generally well tolerated. Mild moderate dose-dependent gastrointestinal complaints the most frequent adverse events. No relevant QT prolongation noted. Maximum plasma concentrations lower than MICs. Exposure (AUC0-24) increased by accumulation upon repeated administration monotherapy groups. Co-administration resulted decreasing exposures from day 1 14. A higher (300 mg) dose largely outweighed evolving inductive rifampicin. The fall log cfu/mL (95% CI) 0.093 (0.126-0.059) rifampicin, 0.133 (0.166-0.100) 0.089 (0.121-0.057) SQ109. Treatments showed no significant activity. CONCLUSIONS: Upon co-administration yielded exposure dose. did not appear be active enhance activity during days treatment.