AZD 5847 Early Bactericidal Activity - DMID 11-0006

Randomized, Open Label, Multiple Dose Phase 2a Study of the Early Bactericidal Activity of AZD5847 in Adults with Pulmonary Tuberculosis

Information:

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
Study Period 2012-2015

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.

Primary Objective:

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.

Secondary Objective:

  1. 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.
  2. 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.
  3. To compare the results of sputum MTB mRNA clearance with the results of the above EBA measurements.
  4. To compare the results of changes in urine, sputum and serum host and MTB metabolites with the results of the above EBA measurements.
  5. To determine the pharmacokinetics and pharmacodynamics of the study drug AZD5847 in subjects with smear positive pulmonary TB.
  6. To demonstrate that lack of EBA activity is not due to low serum drug concentrations.
  7. To evaluate the safety and tolerability of AZD 5847 in the study population at the study doses.