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WHAT'S NEW THIS WEDNESDAY: A NOVEL TB TREATMENT, PHASE 2 TRIALS IN SOUTH AFRICA

Tuesday, 24th of July 2012

• A PHASE 2 TRIAL OF NOVEL ANTI-TUBERCULOSIS REGIMENS WITH INCREASED EFFICACY AND LOW POTENTIAL TO INTERACT ADVERSELY WITH ANTIRETROVIRAL THERAPY

Presented by Stephen Murray (United States).

D. Everitt¹, S. Murray², A. Diacon³, R. Dawson⁴, J. Hutchings⁴, C. Van Niekerk⁵, E. Egizi², P. Becker<sup>6

1</sup>TB Alliance, Research & Development, New York, United States, ²TB Alliance, New York, United States, ³Stellenbosch University, Cape Town, South Africa, ⁴University of Cape Town, Cape Town, South Africa, ⁵TB Alliance, Pretoria, South Africa, ⁶Medical Research Council of South Africa, Johannesburg, South Africa

Also accessible at http://pag.aids2012.org/abstracts.aspx?aid=16412

Abstract:

Background: PA-824 (Pa) and bedaquiline (B) (TMC) are novel compounds in phase 2 development with established Early Bactericidal Activity (EBA) over 14 days. The study presented is an EBA study that evaluated these drugs alone or in combination with each other and with moxifloxacin (M) and pyrazinamide (Z) to identify a regimen with the potential to shorten treatment of TB in patients without the use of rifamycins or other drugs that interact adversely with antiretroviral Therapy (ART).

Methods: 83 participants enrolled (26% F, 74% M, including 6 HIV+) as five cohorts of 15 TB patients, each who received daily dosages of B alone, B with Z, B with Pa, Pa with Z and Pa with M and Z. A cohort of 8 patients received daily standard TB treatment (isoniazid, rifampin, Z and ethambutol: HRZE) as a control for the EBA quantitative mycobacteriology. The primary efficacy endpoint was the rate of change in number of colony forming units (CFU) of Mycobacterium tuberculosis per ml of sputum incubated on agar plates from serial sputum collections over the period Day 0 to Day 14.

Results: All cohorts had decreases in logCFU counts/ml of sputum from Days 0 to 14 that ranged from 1.2 - 2.7 over 14 days. While Z potentiated the activity of both B and Pa and compared favorably with the HRZE standard regimen, the cohort with the combination Pa-M-Z had numerically the greatest effect on CFU reduction.

Conclusions: The combination regimen of Pa-M-Z has potent bactericidal activity over 14 days in patients with pulmonary TB and has the potential to treat both Drug Sensitive- and Drug Resistant-TB (contains no INH or rifampicin) without adverse clinical interactions with ART. This regimen has been taken into an 8 week trial to treat DS- and DR-TB in patients with and without HIV infection.