Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis

NCT00760149 | Completed Phase 2 DMC

• 2 other identifiers: APRIORI 4.1PACTR2009060001493909
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase II clinical trial, the pharmacokinetics, safety and (short-term) efficacy of higher than standard doses rifampicin will be studied during the intensive phase of tuberculosis (TB) treatment. Patients enrolled in this study will either get the standard TB regimen (including 600 mg rifampicin; first study arm), or 900 mg rifampicin plus isoniazid, ethambutol and pyrazinamide in standard dosages (second study arm), or 1200 mg rifampicin plus the other drugs in standard dosages (third study arm). All patients will get the standard TB regimen during the continuation phase of treatment.

Conditions

Tuberculosis

Keywords

tuberculosis; rifampicin; pharmacokinetics; pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic parameters of rifampicin, desacetylrifampicin, isoniazid, pyrazinamide, ethambutol

  Steady state, week 6

Secondary Outcomes (4)

• Occurrence of adverse events

  baseline, week 1, 2, 4, 6, 8, 10, 12

• Bacteriological response of Mycobacterium tuberculosis

  Almost daily during first 8 weeks

• Compare accuracy of surrogate markers (SSCC, mRNA, cytokines) with standard two-month sputum conversion marker

  Almost daily during first 8 weeks

• Documenting the occurrence of mixed Mycobacterium tuberculosis strain infections

  Almost daily during first 8 weeks

Study Arms (3)

1

PLACEBO COMPARATOR

50 patients, treated with the standard anti-TB regimen, including rifampicin (600 mg), isoniazid (300 mg), pyrazinamide (30 mg/kg), ethambutol (15 mg/kg), administered daily, orally, during the intensive phase of TB treatment. In addition they will receive 2 placebo tablets resembling rifampicin 300 mg.

Drug: Rifampicin in higher doses

2

ACTIVE COMPARATOR

50 patients, treated with rifampicin (900 mg), and the other drugs in standard dosages (isoniazid (300 mg), pyrazinamide (30 mg/kg), ethambutol (15 mg/kg)), administered daily, orally, during the intensive phase of TB treatment. In addition they will receive 1 placebo tablet resembling rifampicin 300 mg.

Drug: Rifampicin in higher doses

3

ACTIVE COMPARATOR

50 patients, treated with rifampicin (1200 mg), and the other drugs in standard dosages (isoniazid (300 mg), pyrazinamide (30 mg/kg), ethambutol (15 mg/kg)), administered daily, orally, during the intensive phase of TB treatment.

Drug: Rifampicin in higher doses

Interventions

Rifampicin in higher doses DRUG

Rifampicin 900 mg (study arm 2), and rifampicin 1200 mg (study arm 3)

1; 2; 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has a newly diagnosed pulmonary tuberculosis, confirmed by a positive smear of at least two sputum specimens with ZN staining.
• Participant is willing to be tested for HIV.
• Participant is at least 18, but not more than 65 years of age at the day of the first dosing of study medication.
• Participant is admitted to KNTH or KCMC during the intensive phase of TB treatment.
• Participant is able and willing to attend to KNTH or KCMC regularly during the continuation phase of TB treatment.
• Participant is able to understand and willing to sign the Informed Consent Form prior to screening evaluations.
• Female participants should understand that it is important not to get pregnant during the study. They should agree on taking measures to prevent them from getting pregnant during the study. They should agree on taking measures to prevent them from getting pregnant, such as using a contraceptive device or barrier method.

You may not qualify if:

• Participant has been treated with anti-tuberculosis drugs during the past three years.
• Participant's body weight is less than 50 kg.
• Participant has abnormal liver function test or serum creatinine (defined as levels higher than the upper limit of normal).
• Participant has a relevant medical history or current condition that might interfere with drug absorption, distribution, metabolism or excretion (i.e. chronic gastro-intestinal disease, Diabetes Mellitus, renal or hepatic disease, use of concomitant drugs that interfere with the pharmacokinetics of anti-TB drugs).
• Participant has a CD4 count less than 350 cells/mm3.
• Participant has a Karnofsky score of less than 40.
• Participant is pregnant or breastfeeding.
• Participant has a Multi Drug Resistant (MDR)-TB for which another than the standard treatment regimen is needed.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• Sanofi: collaborator
• Kilimanjaro Christian Medical Centre, Tanzania: collaborator
• Kibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania: collaborator
• University Centre for Chronic Diseases Dekkerswald, Groesbeek, The Netherlands: collaborator
• National Institute for Public Health and the Environment (RIVM): collaborator

Study Sites (1)

Kibong'oto National Tuberculosis Hospital

Sanya Juu, Kilimanjaro, P.O. box 12, Tanzania

Location

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MeSH Terms

Conditions

Tuberculosis

Interventions

Rifampin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Rob Aarnoutse, Pharm-D, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Gibson Kibiki, MD, MMed, PhD

  Kilimanjaro Christian Medical Centre,Moshi,Tanzania

  PRINCIPAL INVESTIGATOR

• Martin Boeree, MD PhD

  Radboud University Nijmegen Medical Center/UCCZ Dekkerswald

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 25, 2008
• First Posted: September 26, 2008
• Study Start: July 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 9, 2013

Record last verified: 2013-09

Locations

TA (1)