Clinical studies on bedaquiline
First author [ref.], year | Type of study | Study number | Subjects taking bedaquiline n | Efficacy findings | Tolerability findings | QTc effect | Notes |
Diacon [52], 2009 | Phase IIb, randomised, multicentre, double-blind, placebo- controlled study | C208 stage 1 | 23 | Bedaquiline reduced the time to conversion to a negative sputum culture Bedaquiline increased the proportion of patients with conversion of sputum culture | Most AEs were mild to moderate; only nausea occurred significantly more frequently in the bedaquiline group | QT interval prolongation was observed in the bedaquiline and placebo group (more pronounced in the bedaquiline group), with intergroup differences ranging from 1.0 to 10.8 ms (p>0.05) None of the absolute values for the corrected QT interval exceeded 500 ms, and no adverse events were associated with ECG changes | |
Diacon [53], 2014 | Phase IIb, randomised, multicentre, double-blind, placebo- controlled study | C208 stage 2 | 79 | Bedaquiline reduced the median time to culture conversion from 125 days to 83 days | Bedaquiline had similar rates of AEs, treatment-related AEs, and AEs leading to study discontinuation than placebo The most frequent AEs were nausea, arthralgia and vomiting The severity of most adverse events was grade 1 or 2 | At study week 24, the mean change from baseline in the QTcF was an increase of 15.4 ms in the bedaquiline group and an increase of 3.3 ms in the placebo group (p<0.001) After bedaquiline treatment ended, the QTcF gradually decreased, and the mean value was similar to that in the placebo group by study week 60 | |
Guglielmetti [58], 2015 | Retrospective cohort study | 35 | Culture conversion rate was 97% after 6 months of therapy | Mild liver enzyme elevation (≥2-fold from baseline) was reported in 14% of patients, and a ≥5-fold increase occurred in two additional patients (6%) Confounding effect of concomitant drugs was mentioned | QTc prolongation was greater in individuals exposed to bedaquiline and fluoroquinolones, or clofazimine | ||
Ndjeka [59], 2015 | Interim cohort analysis | 91 (54 HIV+) | In total, 48 (76%) out of 63 patients with 6 months of follow-up either achieved culture conversion or remained culture-negative 6 months after initiation of bedaquiline | Good profile | Clofazimine use and not HIV infection was associated with QTc increase | ART based on either lopinavir/ritonavir or nevirapine | |
Pym [46], 2015 | Phase 2, multicentre, multinational, open-label, noncomparative, single-arm trial | C209, NCT00910871 | 233 | Culture conversion was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively | The commonest AEs were similar to those generally reported in MDR-TB treatment cohorts; most were grade 1 or 2 Hyperuricaemia and increased aspartate aminotransferase were the most frequent grade ≥3 AEs The incidence of AEs was highest during the first 12 weeks Serious AEs were reported in 47 (20.2%) patients: respiratory infections/disorders were the most common | Prolongation of the QTcF interval was reported infrequently Two patients had an increase in QTcF interval >500 ms; they were both taking clofazimine, and one had concurrent hypokalaemia No episodes of clinically significant dysrhythmia were reported | Two deaths were considered doubtfully related to bedaquiline |
AEs: adverse events; QT interval: measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTc: QT interval corrected; QTcF: QT interval corrected by Fridericia's formula; MDR-TB: multidrug-resistant tuberculosis; XDR-TB: extensively drug-resistant tuberculosis.