Safety, Tolerability, Extended Early Bactericidal Activity and PK of Higher Doses Rifampicin in Adults With Pulmonary TB

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.

Conditions

• Pulmonary Tuberculosis (TB)

Interventions

DRUG

Rifampicin

High dose rifampicin

Sponsors & Collaborators

• European and Developing Countries Clinical Trials Partnership (EDCTP)

  collaborator OTHER_GOV

• Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands.

  collaborator OTHER

• University Centre for Chronic Diseases Dekkerswald, Groesbeek, NL

  collaborator UNKNOWN

• Radboud University Medical Center

  lead OTHER

Principal Investigators

• Martin Boeree, MD, PhD · Radboud university medical center, University Centre for Chronic Deseases Dekkerswald

• Rob Aarnoutse, PharmD, PhD · Radboud University Medical Center

• Andreas Diacon, MD · TASK Applied Science

• Rodney Dawson, MD · University of Cape Town Lung Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-06-30

Primary Completion

2018-07-31

Completion

2018-11-30

Countries

• South Africa

Study Locations