E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
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 |
The primary objective is to describe and compare the incidence of hepatotoxicity in standard care and in a regimen with an optimized dose of 1800 mg rifampicin in patients with rifampicin-susceptible tuberculosis. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: • To compare any adverse events in the optimized dose regimen versus the standard dose regimen. • To compare final treatment outcome at the end of treatment according to WHO definitions of cure in the optimized dose regimen versus the standard dose regimen. • To compare two and three months culture conversion rates in the optimized dose regimen versus the standard dose regimen. • To describe and compare the steady-state plasma pharmacokinetics of the optimized dose regimen versus the standard dose regimen. This will be performed depending on the availability of pharmacological analyses.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The patient has a diagnosis of pulmonary tuberculosis according to the local diagnostic criteria. The patient is aged 18 years or older at the day of informed consent. No known allergic reactions or toxicity to rifampicin in the past. |
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E.4 | Principal exclusion criteria |
Patient infected with a rifampicin-resistant strain of M. tuberculosis. The patient has TB meningitis. The patient is in a coma. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of hepatotoxicity, which will be compared between treatment arms at the end of the 6 months treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the 6 months treatment. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are: • The proportion of adverse events overall and graded by severity assessed to be related or probably related to rifampicin during the 6 months treatment will be compared between treatment arms. • Final treatment outcome at the end of treatment according to WHO definitions of cure will be compared between treatment arms. • Two and three months culture conversion rates will be compared between treatment arms. • Steady-state plasma pharmacokinetic parameters will be compared between treatment arms.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- The proportion of adverse events overall and graded by severity assessed to be related or probably related to rifampicin during the 6 months treatment will be compared between treatment arms. - Final treatment outcome at the end of treatment (6 months) according to WHO definitions of cure will be compared between treatment arms. -Two and three months culture conversion rates will be compared between treatment arms. This outcome is evaluated at two and three months. - Steady-state plasma pharmacokinetic parameters will be compared between treatment arms, at day 14.
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard tuberculosis treatment: Control arm with the daily standard regimen for 6 months: 2HRZE/4HR |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |