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Karel de Beule, CDTL TMC 207

Interim analysis of a double-blind, placebo-controlled study with TMC207 in patients with Multi-Drug Resistant (MDR) Tuberculosis. Karel de Beule, CDTL TMC 207. TMC207-C208 Trial Design. Phase II, placebo-controlled, double-blind Patients with newly diagnosed smear positive MDR-TB

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Karel de Beule, CDTL TMC 207

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  1. Interim analysis of a double-blind, placebo-controlled study with TMC207 in patients with Multi-Drug Resistant (MDR) Tuberculosis Karel de Beule, CDTL TMC 207

  2. TMC207-C208 Trial Design • Phase II, placebo-controlled, double-blind • Patients with newly diagnosed smear positive MDR-TB • Stratified by trial site and degree of lung cavitation • 2 stage trial design • Stage 1 - Safety and dose determination • 8 weeks dosage TMC207/placebo and BR, then BR and 24 months follow-up • Dose regimen: 400 mg qd for 2 weeks followed by 200 mg three times weekly for 6 weeks • Stage 2 - Recruiting - full 6 month dosage • This presentation is a pre-planned analysis of the stage 1 results after 8 weeks of treatment

  3. Stage 1 Objectives • Primary • Evaluate PK (adequacy of the model predicted exposure) • Evaluate safety and tolerability of TMC207 compared to placebo • Secondary • Evaluate anti-bacterial activity of TMC207at 8 wks vs placebo

  4. Inclusion/Exclusion Criteria • Male and female 18-65 years • Positive sputum smear > 1+ • Confirmed resistance to H and R • HIV negative or HIV+ with CD4+ > 300 and no ART • No previous 2nd line anti-tuberculosis agents • No significant extrapulmonary TB or concomitant illness

  5. Demographics

  6. Background Regimen

  7. PK of TMC207 vs model predictions CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

  8. Most frequent Adverse Events CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

  9. Safety CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

  10. Microbiology parameters • Weekly sputum collection - culture conversion in liquid media • Defined as 2 consecutive negative cultures at least 1 week apart • Drug carry-over effects were prevented • Analysis set = 44 patients (3 withdrawals) • Serial sputum colony counting (SSCC) performed in 22 patients in overnight sputum collections

  11. Culture conversion in liquid media CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

  12. Mean log10 CFU count over time CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

  13. Conclusions CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

  14. Acknowledgements • - The patients who participated in our study • - Dr. Andreas Diacon and team, Stellenbosch University, Cape Town • - Dr. Alexander Pym and team Medical Research Council, Durban • - Dr. Martin Grobusch and team, University of the Witwatersrand • - Dr. Martin Bogoshi and team, Aurum Health, South Africa • - Dr. Renée Krause, C. Pistorius and team, QdotPharma, South Africa • -Members of the TMC207 compound development and clinical teams, Tibotec, Yardley, PA (USA) and Mechelen, Belgium.

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