Clinical studies on bedaquiline

First author [ref.], yearType of studyStudy numberSubjects taking bedaquiline nEfficacy findingsTolerability findingsQTc effectNotes
Diacon [52], 2009Phase IIb, randomised, multicentre, double-blind, placebo- controlled studyC208 stage 123Bedaquiline 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 groupQT 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], 2014Phase IIb, randomised, multicentre, double-blind, placebo- controlled studyC208 stage 279Bedaquiline reduced the median time to culture conversion from 125 days to 83 daysBedaquiline 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], 2015Retrospective cohort study 35Culture conversion rate was 97% after 6 months of therapyMild 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], 2015Interim 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 bedaquilineGood profileClofazimine use and not HIV infection was associated with QTc increaseART based on either lopinavir/ritonavir or nevirapine
Pym [46], 2015Phase 2, multicentre, multinational, open-label, noncomparative, single-arm trialC209, NCT00910871233Culture 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, respectivelyThe 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.