High Dose Rifapentine Pharmacokinetics, Tolerability and Safety Dosage Rifapentine for Treatment of Tuberculosis (TBTC-29PK)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01043575
First received: January 6, 2010
Last updated: August 15, 2012
Last verified: August 2012
  Purpose

The primary objective of this study is to characterize rifapentine drug levels in patients with TB in relationship to its effectiveness in treating TB and any adverse effects experienced by participants.


Condition Intervention Phase
Smear Positive, Pan-sensitive, Pulmonary Tuberculosis
Drug: Rifapentine
Drug: Rifampin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic and Pharmacodynamic Studies of Efficacy, Tolerability and Safety of Higher Dosage Rifapentine for Treatment of Tuberculosis

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • The primary objective of this study is to characterize rifapentine pharmacokinetic parameters (AUC0-24 and peak concentration) in patients with TB. [ Time Frame: on or after the 10th day from the start of Study 29 therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • • To assess the pharmacodynamic effects of higher dose, daily rifapentine AUC0-24 on tolerability and safety during two months of treatment of tuberculosis. [ Time Frame: on or after the 10th day of study therapy ] [ Designated as safety issue: Yes ]
  • • To assess the pharmacodynamic effect of rifapentine pharmacokinetic parameters (AUC0-24) on biomarkers of treatment activity in patients with tuberculosis. [ Time Frame: on or after the 10th day of study therapy ] [ Designated as safety issue: No ]
  • • To assess in multivariate analyses the pharmacodynamic effect on biomarkers of treatment activity of the independent variables of rifapentine AUC0-24, HIV infection, isoniazid exposure (AUC0-12) and study site (African vs. non-African). [ Time Frame: on or after the 10th day of study therapy ] [ Designated as safety issue: No ]
  • To determine if free (non-protein bound) rifapentine and free rifampin exposures are directly associated with anti-mycobacterial activity. [ Time Frame: on or after the 10th day of study therapy ] [ Designated as safety issue: No ]
  • • To determine the effects of polymorphisms of transporter genes on rifampin and rifapentine pharmacokinetic parameters. [ Time Frame: on or after the 10th day of therapy ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: April 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Rifapentine
Drug: Rifapentine
During the first 8 weeks of therapy for TB participants > 45 kg will receive rifapentine 600 mg orally given 5 per week and for participants < 45 kg participants will receive 450 mg orally given 5 days per week
Other Name: Priftin
Active Comparator: 2
Rifampin
Drug: Rifampin
During the first 8 weeks of therapy participants will receive rifampin at standard doses (e.g. 600 mg) 5 days per week

Detailed Description:

This is a one-period, non-blinded, multi-center pharmacokinetic substudy of rifapentine and rifampin in patients with tuberculosis enrolled in Tuberculosis Trials Consortium (TBTC) Study 29. This PK substudy will use a convenience sample, i.e. be restricted to TBTC sites having logistical capacity for intensive pharmacokinetic sampling. These sites will have non-random selection of patients. In addition to the intensive sampling of 60 patients in this PK study, all patients receiving rifapentine in Study 29 will be eligible for sparse PK sampling as part of the parent treatment protocol.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Any patient enrolled in TBTC Study 29.
  • Provision of informed consent for the study.
  • Willingness to be sampled in an out-patient clinic or be admitted to a General Clinical Research Center (GCRC) or hospital on one occasion

Exclusion Criteria:

• Severe anemia as defined by a hematocrit less than 25% (most recent value, measured within 30 days of the PK study).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01043575

Locations
United States, Colorado
Denver Public Health
Denver, Colorado, United States
United States, Texas
University of North Texas
Denton, Texas, United States
TBTC site 40 / South Texas
Harlingen, Texas, United States
Audie L. Murphy VA Medical Center
San Antonio, Texas, United States
South Africa
University of KwaZulu Natal
Durban, South Africa
Uganda
Uganda / Case Western Reserve Research Collaboration
Kampala, Uganda
Sponsors and Collaborators
Investigators
Principal Investigator: Marc Weiner, MD University of Texas Health Sciences Campus, San Antonio
  More Information

No publications provided

Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01043575     History of Changes
Other Study ID Numbers: TBTC Study 29PK
Study First Received: January 6, 2010
Last Updated: August 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Centers for Disease Control and Prevention:
rifapentine, pharmacokinetics, pharmacodynamics, tuberculosis

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Rifampin
Rifapentine
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 29, 2014