Study of Daily Rifapentine for Pulmonary Tuberculosis

NCT00814671 | Completed Phase 2 Results DMC

• 1 other identifier: NA_00019095
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this Phase 2 study is to determine the microbiological activity and safety of rifapentine when given as a component of multidrug intensive phase treatment of smear-positive pulmonary tuberculosis (TB). Funding Source- FDA Office of Orphan Products Development (OOPD)

Conditions

Tuberculosis

Keywords

Tuberculosis; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8

  8 weeks

• Tolerability

  percentage of participants discontinuing assigned treatment

  10 weeks

Secondary Outcomes (3)

• Time to Stable Culture Conversion on Solid Medium

  12 weeks

• Time to Stable Culture Conversion on Liquid MGIT Media

  12 weeks

• Pharmacokinetics of Rifapentine

  8 weeks

Study Arms (3)

RPT450

EXPERIMENTAL

Rifapentine 450mg daily

Drug: Rifapentine 450

RIF 600

ACTIVE COMPARATOR

Rifampin 600mg daily

Drug: Rifampin

RPT 600

EXPERIMENTAL

Rifapentine 600mg daily

Drug: Rifapentine 600

Interventions

Rifapentine 450 DRUG

rifapentine 450 mg

Also known as: Priftin

RPT450

Rifapentine 600 DRUG

rifapentine 600 mg

Also known as: Priftin

RPT 600

Rifampin DRUG

rifampin 600 mg

Also known as: Rifampacin

RIF 600

Eligibility Criteria

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

You may qualify if:

• Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated sputum. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment.
• No prior history of tuberculosis disease or tuberculosis treatment
• No treatment with fluoroquinolones in the 2 months preceding initiation of study drugs.
• Age \> 18 years
• Weight ≥ 50 kg and ≤ 80 kg
• Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix)
• Signed informed consent
• Ability to adhere with study follow-up
• Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy.
• HIV negative, or HIV-positive with CD4 \> 200 cells/cu mm
• Laboratory parameters done at, or 14 days prior to, screening (with results available for review by study personnel):
• Serum alanine aminotransferase (ALT) activity ≤ 2 times the upper limit of normal
• Serum total bilirubin level ≤ 2 times the upper limit of normal
• Serum creatinine level less than or equal to the upper limit of normal
• Hemoglobin level of at least 7.0 g/dL

You may not qualify if:

• Pregnant or breast-feeding
• Known intolerance or allergy to any of the study drugs
• Concomitant disorders or conditions for which isoniazid (INH), rifamycins, pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
• Current or planned therapy, during the intensive phase of TB therapy with cyclosporine or tacrolimus, or HIV antiretroviral (ARV) therapy, which have unacceptable interactions with rifamycins.
• Any medical or psychosocial condition, which, in the view of the study investigator, makes study participation inadvisable.
• Pulmonary silicosis
• Central nervous system TB

Sponsors & Collaborators

• Johns Hopkins University: lead
• University of Cape Town Lung Institute: collaborator
• University of Cape Town: collaborator

Study Sites (1)

Universiy of Cape Town Lung Institute

Cape Town, Western Cape, 7937, South Africa

Location

Related Publications (2)

• Rosenthal IM, Williams K, Tyagi S, Peloquin CA, Vernon AA, Bishai WR, Grosset JH, Nuermberger EL. Potent twice-weekly rifapentine-containing regimens in murine tuberculosis. Am J Respir Crit Care Med. 2006 Jul 1;174(1):94-101. doi: 10.1164/rccm.200602-280OC. Epub 2006 Mar 30.

  PMID: 16574936 RESULT

• Rosenthal IM, Williams K, Tyagi S, Vernon AA, Peloquin CA, Bishai WR, Grosset JH, Nuermberger EL. Weekly moxifloxacin and rifapentine is more active than the denver regimen in murine tuberculosis. Am J Respir Crit Care Med. 2005 Dec 1;172(11):1457-62. doi: 10.1164/rccm.200507-1072OC. Epub 2005 Sep 1.

  PMID: 16141439 RESULT

MeSH Terms

Conditions

Tuberculosis

Interventions

rifapentine; 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

Results Point of Contact

• Title: Susan Dorman
• Organization: Johns Hopkins University

dsusan1@jhmi.edu

410-955-1755

Study Officials

• Susan Dorman, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2008
• First Posted: December 25, 2008
• Study Start: April 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: September 1, 2014
• Last Updated: February 6, 2018
• Results First Posted: September 28, 2016

Record last verified: 2018-01

Locations

ZA (1)