Safety, Tolerability, Extended Early Bactericidal Activity and PK of Higher Doses Rifampicin in Adults With Pulmonary TB
Condition: Pulmonary Tuberculosis (TB)
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional
Phase: Phase 2

Summary: 
      This is the first trial in a series of clinical trials that aim to bring the concept of high
      dose rifampicin beyond phase II of clinical development.

      The safety, tolerability, extended early bactericidal activity (EBA) and pharmacokinetics of
      several doses of Rifampicin with or without standard doses of Isoniazid, Pyrazinamide and
      Ethambutol in adults with newly diagnosed, uncomplicated, smear positive, pulmonary TB will
      be assessed. The objective of this study is to find the maximum tolerable dose of Rifampicin
      as monotherapy and in combination with the currently available Isoniazid, Pyrazinamide and
      Ethambutol.

      The subjects will be in the study for 24-31 days. After a screening period of 9-3 days, the
      subjects will receive treatment with Rifampicin as single drug during 7 days (monotherapy).
      This treatment will be followed by treatment with 7 days of Rifampicin and Isoniazid,
      Pyrazinamide and Ethambutol (combination therapy), and 7-8 days treatment with standard TB
      medication.

      All subjects will be closely monitored for side effects. This monitoring will include daily
      interviews and physical examination, and ECG evaluation and blood and urine analyses at
      specific intervals.

      During the 7 days of monotherapy, after the second day of the combination therapy and at the
      end of the combination therapy, overnight sputum will be collected from the patients to
      investigate the potency of high dose rifampicin to reduce this number of bacilli.

      The Rifampicin dose will be increased step by step and group by group. The control group will
      receive the standard dose of 10 mg Rifampicin/kg, whereas the first treatment group will
      receive 20 mg/kg. The Rifampicin dose will only be further increased for a next group of
      patients, if this is expected to be safe.

      Rifampicin is widely available and not expensive. Physicians all over the world have
      experience with this drug and its adverse effects. Should this study be successful, the
      highest dose of Rifampicin that this safe and tolerable will be given to a larger group of
      patients. in the next study.

      If increasing the dose of Rifampicin proves to be safe and effective, a higher dose of
      Rifampicin could be implemented broadly and quickly, and it would benefit many patients
      worldwide.
    


Intervention name(s): Rifampicin
Intervention type(s): Drug
Intervention description(s): High dose rifampicin
Other intervention name(s): Rifadin; Rifafour
Intervention MeSH terms: Rifampin
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dose Ranging; Extended Early Bactericidal Activity; Maximum tolerable dose; Pharmacokinetics; Pulmonary Tuberculosis; Rifampicin; Rifafour; Safety; Tolerability; Max Tolerable Dose