Moxifloxacin As Part of a Multi-Drug Regimen For Tuberculosis

Official Title: “Phase 2 Randomized Trial of a Moxifloxacin-Containing Regimen For Treatment of Smear-Positive Pulmonary Tuberculosis in Adults With and Without HIV Infection”

Current treatment of tuberculosis (TB) requires patients to take four drugs for 8 weeks and then two drugs for 4 months. New drug regimens that are shorter and effective against drug-resistant TB are needed. This study will evaluate whether using the drug moxifloxacin (MOX) in place of ethambutol (EMB) during the first 8 weeks of treatment will effectively treat TB.

Approximately one-third of the world's population is infected with Mycoplasma tuberculosis; 7 to 8 million new cases of active TB occur each year. TB is the second most common infectious cause of death worldwide. Appropriate treatment of persons with active TB is very important in limiting the transmission of M. tuberculosis and preventing TB-related mortality. Current therapy requires 6 months of a four-drug regimen of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and EMB.

The development of alternative regimens is a priority, and new classes of antituberculosis agents are needed to provide treatment options for patients with drug-resistant disease.

This study will evaluate the effectiveness of replacing EMB with MOX in a multi-drug regimen in the initial phase of treatment of smear-positive pulmonary TB in patients with and without HIV infection.

Participants in this study will be randomly assigned to receive either a MOX-containing drug regimen or the standard EMB-containing drug regimen for 8 weeks. Participants will have study visits weekly during these 8 weeks. After 8 weeks, participants will discontinue MOX, EMB, and PZA and will continue taking INH and RFP for 4 months. Participants will have study visits at Months 4, 6, 12, and 18. Study visits will include a medical interview, physical exam, blood and urine tests, and sputum tests for TB.

Intervention(s) in this Clinical Trial

• Drug: Moxifloxacin
  • 400mg daily for 8 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • INH 300mg/RIF 600mg/PZA 20mg/kg/MOX 400mg/EMB placebo once daily for 8 weeks
• Placebo Comparator: 2
  • INH 300mg/RIF 600mg/PZA 20mg/kg/MOX placebo/EMB 15-20mg/kg once daily for 8 weeks

Primary Measures

• Proportion of patients with sterile sputum cultures
  • Time Frame: 8 weeks
    Safety Issue?: No

Secondary Measures

• Proportion of patients with Grade 3 or 4 adverse reactions attributable to study medications
  • Time Frame: 8 weeks
    Safety Issue?: Yes
• Proportion of patients with sterile sputum
  • Time Frame: 4 weeks
    Safety Issue?: No
• Proportion of patients with any grade 3 or 4 adverse reaction
  • Time Frame: 6 months
    Safety Issue?: Yes

Inclusion Criteria:

• Presumptive diagnosis of smear-positive pulmonary TB within 2 weeks of study entry.
• Patients with both pulmonary and extrapulmonary disease are eligible.
• Documentation of HIV infection status. If HIV status is unknown at study entry, the participant must consent to testing and results must be available prior to study participation.
• Agree to use acceptable methods of contraception

Exclusion Criteria:

• History of adverse drug reaction to MOX, INH, RIF, PZA, or EMB
• Disease or condition for which MOX, INH, RIF, PZA, or EMB is contraindicated
• History of more than 14 days of continuous antituberculosis therapy during the previous 2 years or more than 2 months of antituberculosis therapy ever
• Active AIDS-related opportunistic infection or malignancy
• Currently receiving or planning to receive HIV protease inhibitors or nonnucleoside reverse transcriptase inhibitors in the first 2 months after study entry
• Silicotuberculosis
• Central nervous system TB
• Pregnant or breastfeeding
• Unable to take oral medication
• Electrocardiogram (EKG) QTc interval greater than 450 msec
• Taking classes IA or III antiarrhythmic agents (quinidine, procainamide, amiodarone, sotalol), cisapride, erythromycin, perphenazine/amitriptyline, phenothiazines, or tricyclic antidepressant
• Diseases or conditions for which treatment with other drugs with antituberculosis activity (e.g., rifabutin for MAC prophylaxis) is anticipated during the course of the study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Food and Drug Administration (FDA) U.S. Fed

Overall Clinical Trial Officials and Contacts

Richard E. Chaisson, MD Principal Investigator Johns Hopkins University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00082173

Study ID Number: FD-R-002135-01

ClinicalTrials.gov Identifier: NCT00082173

Health Authority: United States: Food and Drug Administration