Evaluation of a Moxifloxacin-Based, Isoniazid-Sparing Regimen for Tuberculosis Treatment (Study 28); Pharmacokinetic Issues in the Use of Moxifloxacin for Treatment of Tuberculosis (Study 28PK)
Sponsor - U.S. Centers for Disease Control & Prevention - Tuberculosis Trials Consortium
Principal Investigator - John L. Johnson, MD, CWRU
|Type of Study||Phase 2 clinical trial of TB treatment with pharmacokinetic and surrogate biomarker sub-studies|
|Design||Phase 2 multi-center, randomized, placebo-controlled, double blind clinical trial evaluating the effect of using moxifloxacin in place of isoniazid, in combination with rifampin, pyrazinaminde and ethambutol on 2-month culture conversion rates among HIV-infected and uninfected patients with sputum smear-positive pulmonary TB with PK sub-studies|
|Sample Size||Study 28: 410 subjects; Uganda Enrollment: 202
Study 28PK: 70 subjects; Uganda Enrollment: 40
|Population||HIV-infected and uninfected adults with initial episodes of newly diagnosed smear-positive, pulmonary TB|
|Study Period||February 2006-September 2008|
|Interactions||Collaborating investigators/staff, utilizing shared infrastructure|
TBTC Study 28 & 28X:
Current 6-month duration TB treatment regimens are challenging for patients and tuberculosis control programs. Therefore, a high priority in tuberculosis research is the identification of agents that can shorten treatment. Several fluoroquinolone antibiotics have potent activity against MTB in preclinical testing. Of the currently available fluoroquinolones, moxifloxacin has excellent activity in vitro and in animal models of tuberculosis, a favorable pharmacokinetic profile (serum half-life of 10-12 hours), lack of problematic drug-drug interactions, no need for dosage adjustment for renal and hepatic insufficiency, and an excellent safety profile. In addition, in the murine model of tuberculosis, the substitution of moxifloxacin for isoniazid resulted in significant reductions in the time to culture conversion and the time to sterilization when compared to the standard combination rifampin, isoniazid, and pyrazinamide. However, moxifloxacin has not been fully evaluated in humans for tuberculosis treatment. There is a need to assess not only the anti-tuberculosis activity of moxifloxacin-containing regimens, but also the safety of more prolonged therapy with moxifloxacin.
Final results of this completed study can be found in the following publication:
Dorman SE, Johnson JL, Goldberg S, Muzanye G, Padayatchi N, Bozeman L, Heilig CM, Bernardo J, Choudhri S, Grosset JH, Guy E, Guyadeen P, Leus MC, Maltas G, Menzies D, Nuermberger EL, Villarino M, Vernon A, Chaisson RE; Tuberculosis Trials Consortium. Substitution of Moxifloxacin for Isoniazid during Intensive Phase Treatment of Pulmonary Tuberculosis Am J Respir Crit Care Med. 2009; 180:273-280.