High Dose Rifapentine Pharmacokinetics, Tolerability and Safety Dosage Rifapentine for Treatment of Tuberculosis

Smear Positive, Pan-sensitive, Pulmonary Tuberculosis Clinical Trial

— TBTC-29PK  

Official title:

Pharmacokinetic and Pharmacodynamic Studies of Efficacy, Tolerability and Safety of Higher Dosage Rifapentine for Treatment of Tuberculosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01043575
• Other study ID #: TBTC Study 29PK
• Status: Completed
• Phase: Phase 2
• First received: January 6, 2010
• Last updated: August 15, 2012
• Start date: April 2009
• Est. completion date: May 2010

Study information

• Verified date: August 2012
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Smear Positive, Pan-sensitive, Pulmonary Tuberculosis
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

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
• Rifampin
During the first 8 weeks of therapy participants will receive rifampin at standard doses (e.g. 600 mg) 5 days per week

Locations

Country	Name	City	State
South Africa	University of KwaZulu Natal	Durban
Uganda	Uganda / Case Western Reserve Research Collaboration	Kampala
United States	University of North Texas	Denton	Texas
United States	Denver Public Health	Denver	Colorado
United States	TBTC site 40 / South Texas	Harlingen	Texas
United States	Audie L. Murphy VA Medical Center	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention

Countries where clinical trial is conducted

United States,  South Africa,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective of this study is to characterize rifapentine pharmacokinetic parameters (AUC0-24 and peak concentration) in patients with TB.		on or after the 10th day from the start of Study 29 therapy	No
Secondary	• To assess the pharmacodynamic effects of higher dose, daily rifapentine AUC0-24 on tolerability and safety during two months of treatment of tuberculosis.		on or after the 10th day of study therapy	Yes
Secondary	• To assess the pharmacodynamic effect of rifapentine pharmacokinetic parameters (AUC0-24) on biomarkers of treatment activity in patients with tuberculosis.		on or after the 10th day of study therapy	No
Secondary	• 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).		on or after the 10th day of study therapy	No
Secondary	To determine if free (non-protein bound) rifapentine and free rifampin exposures are directly associated with anti-mycobacterial activity.		on or after the 10th day of study therapy	No
Secondary	• To determine the effects of polymorphisms of transporter genes on rifampin and rifapentine pharmacokinetic parameters.		on or after the 10th day of therapy	No