Randomized, Open Label, Multiple Dose Phase 2a Study of the Early Bactericidal Activity of AZD5847 in Adults with Pulmonary Tuberculosis
DMID Protocol Number: 11-006
|Type of Study||Phase 2a Clinical Trial|
|Design||Randomized, Open-Label, Multiple Dose, Phase 2a Clinical Trial|
|Project Site||TASK Applied Science, Cape Town, South Africa|
|Sample Size||75 Subjects|
|Population||Male and female subjects aged 18 to 65 years with initial episodes of newly-diagnosed, drug susceptible , sputum smear positive pulmonary tuberculosis|
Goal of Study:
To evaluate the safety and early bactericidal activity of AZD5847 in subjects with sputum smear-positive pulmonary tuberculosis to better assess the potential role of this compound in TB treatment.
To assess the EBA 0-14 of AZD5847 at four different doses and schedules (500 mg once daily, 500 mg twice daily, 1200 mg once daily, and 800 mg twice daily) in subjects with newly-diagnosed sputum smear-positive pulmonary TB. A total of 75 subjects will be enrolled, with 15 randomized to each AZD5847 study arm or standard treatment with Rifafour. Duration of drug treatment is 14 days.
- To assess the EBA 0-2 and EBA 2-14 of AZD5847 at differing doses and schedules (500 mg once daily, 500 mg twice daily, 1200 mg once daily, and 800 mg twice daily) in subjects with newly-diagnosed sputum smear-positive pulmonary TB.
- To assess the change in time after inoculation until culture detection (time to detection; TTD) in MGIT enriched liquid culture media) over the periods (Day 0 to Day 14, Day 0 to Day 2 and Day 2 to Day 14) TTD data will be recorded and analyzed for the same time points as CFU.
- To compare the results of sputum MTB mRNA clearance with the results of the above EBA measurements.
- To compare the results of changes in urine, sputum and serum host and MTB metabolites with the results of the above EBA measurements.
- To determine the pharmacokinetics and pharmacodynamics of the study drug AZD5847 in subjects with smear positive pulmonary TB.
- To demonstrate that lack of EBA activity is not due to low serum drug concentrations.
- To evaluate the safety and tolerability of AZD 5847 in the study population at the study doses.