E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To compare two treatments for pulmonary tuberculosis |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the culture-conversion rates at the end of the intensive phase of therapy of the moxifloxacin regimen vs. that of the isoniazid regimen |
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E.2.2 | Secondary objectives of the trial |
To compare the safety and tolerability of the moxifloxacin regimen to that of the isoniazid regimen To determine the time to culture-conversion of the moxifloxacin regimen and the isoniazid regimen, using data from 2-, 4-, 6-, and 8-week cultures. To compare the proportion of patients with any Grade 3 or 4 adverse reactions To compare adverse events and 2-month culture conversion rate among HIV-infected patients vs. HIV-uninfected patients To compare the rates of treatment failure of the moxifloxacin regimen to the isoniazid regimen To determine whether there is delayed toxicity attributable to moxifloxacin (toxicity that becomes evident after the 2 months of moxifloxacin therapy)
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Suspected pulmonary tuberculosis with acid-fast bacilli in a stained sputum smear. Patients whose sputum cultures do not grow M. tuberculosis, and those having an M. tuberculosis isolate resistant to isoniazid, rifampin, fluoroquinolones, or any 2 study drugs will be discontinued from the study, but followed for 14 days to detect late toxicities from study therapy. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment. 2. Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 6 months prior to enrollment 3. 14 or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding enrollment 4. 10 or fewer days of treatment with a fluoroquinolone during the 3 months preceding enrollment 5. Age > 18 years 6. Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs) 7. Signed informed consent 8. Women with child bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy. 9. Laboratory parameters done at, or < 14 days prior to, screening: Serum amino aspartate transferase (AST) activity ≤ 3 times the upper limit of normal Serum total bilirubin level ≤ 2.5 times the upper limit of normal Serum creatinine level ≤ 2 times the upper limit of normal Complete blood count with hemoglobin level of at least 7.0 g/dL Complete blood count with platelet count of at least 50,000/mm3 Serum potassium > 3.0 meq/L Negative pregnancy test (for women of childbearing potential)
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E.4 | Principal exclusion criteria |
1. Breast-feeding 2. Known intolerance to any of the study drugs 3. Known allergy to any fluoroquinolone antibiotic 4. Concomitant disorders or conditions for which moxifloxacin, isoniazid, rifampin, pyrazinamide, or ethambutol are contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gout. 5. Current or planned therapy during the intensive phase of tuberculosis treatment using drugs having unacceptable interactions with rifampin (rifabutin can be substituted for rifampin during the continuation phase of therapy) 6. Current or planned antiretroviral therapy during the intensive phase of tuberculosis treatment 7. History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during the intensive phase of tuberculosis treatment. 8. Pulmonary silicosis 9. Central nervous system TB
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The proportion of patients having a negative sputum culture at 2 months of therapy 2. The proportion of patients who discontinue assigned study therapy for any reason during the first 2 months
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |