Clinical Trials

MainTitle

Pharmacokinetics and Safety of Rifabutin 150 mg Once Daily Versus Rifabutin 300 mg Thrice Weekly

This study has been completed
Sponsor
The HIV Netherlands Australia Thailand Research Collaboration

Collaborator
Bamrasnaradura Infectious Diseases Institute
Chulalongkorn University

Information provided by (Responsible Party)
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier
NCT02415985

First received: April 1, 2015
Last updated: February 11, 2020
Last Verified: February 2020
History of Changes
Purpose

Purpose

To describe the pharmacokinetics of rifabutin 150 mg once daily versus rifabutin 300 mg thrice weekly in combination with LPV/r 400/100mg based HAART in HIV/TB infected patients

Condition Intervention Phase
HIV
Tuberculosis

Drug : Lopinavir/r will be supplied by NHSO/GPO
Drug : Rifabutin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Pilot Study of the Pharmacokinetics and Safety of Rifabutin 150 mg Once Daily Versus Rifabutin 300 mg Thrice Weekly With Lopinavir/Ritonavir Based HAART in HIV/TB Co-infected Patients

Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures

  • pharmacokinetics of rifabutin Cmax [ Time Frame: 48 weeks ]
    Cmax The peak plasma concentration of rifabutin after administration
Secondary Outcome Measures:
  • adverse events [ Time Frame: 48 weeks ]
    number of participants with adverse events
  • viral load [ Time Frame: 48 weeks ]
  • CD4 [ Time Frame: 48 weeks ]
    mean CD4 rise from baseline
  • Monodrug resistant TB [ Time Frame: 48 weeks ]
  • death [ Time Frame: 48 weeks ]
  • AIDS event [ Time Frame: 48 weeks ]
  • TB cure [ Time Frame: 48 weeks ]
  • TB relapse [ Time Frame: 48 weeks ]
  • Multidrug-resistant TB (MDR TB) [ Time Frame: 48 weeks ]
  • TB treatment failure [ Time Frame: 48 weeks ]
  • Extensively drug resistant TB (XDR TB) [ Time Frame: 48 weeks ]
  • weight gain [ Time Frame: 48 weeks ]
    change from baseline in weight gain at 48 weeks
  • defervescence [ Time Frame: 48 weeks ]
    change from baseline in defervescence at 48 weeks
  • Karnofsky score [ Time Frame: 48 weeks ]
    change from baseline in Karnofsky score at 48 weeks

Enrollment: 40
Study Start Date: June 2015
Study Completion Date: December 2019
Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: rifabutin 150
rifabutin 150 mg (1 capsule) once daily
Drug: Lopinavir/r will be supplied by NHSO/GPO

200/50 mg tablet LPV/rtv

Other Name: LPV/rtv
Drug: Rifabutin
Other: rifabutin 300
rifabutin 150 mg (2 capsules) 300 mg 3 times a week
Drug: Lopinavir/r will be supplied by NHSO/GPO

200/50 mg tablet LPV/rtv

Other Name: LPV/rtv
Drug: Rifabutin

Detailed Description:

The overall aim of the project is to evaluate rifabutin as a replacement for rifampicin, for the combined treatment of tuberculosis and HIV infection. Rifabutin represents an alternative to rifampicin for HIV infected patients as its half-life is longer and the enzymatic induction effect appears to be less important on the associated ART drugs. This phase II trial is to determine precisely the pharmacokinetics parameters of rifabutin in combination with LPV/r regimens in Thai HIV/TB infected patients, in order to define optimal doses that will be further tested in a larger phase III trial comparing safety, tolerability and efficacy of rifabutin and rifampicin regimens.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 60 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

    1. Confirmed HIV positive after voluntary counseling and testing
    2. Aged >18-60years of age
    3. PI-naïve (NNRTI intolerance/failure) or PI experience ( TB developed during on salvage regimen) without prior PI mutation
    4. Any CD4 cell count
    5. ALT <5 times ULN
    6. Serum creatinine <1.4 mg/dl
    7. Hemaglobin >7 mg/L
    8. TB is diagnosed and planned to receive stable doses of rifabutin containing anti-TB therapy for at least another 4 week period after initiation of ART
    9. No other active OI (CDC class C event), except oral candidiasis or disseminated MAC
    10. Body weight >40kg
    11. Able to provide written informed consent


Exclusion Criteria:
    1. Current use of steroid (except short course steroid for IRIS) and other immunosuppressive agents.
    2. Current use of any prohibited medications related to drug pharmacokinetics.
    3. Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial.
    4. Unlikely to be able to remain in follow-up for the protocol defined period.
    5. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
    6. Karnofsky performance score <30%
    7. TB meningitis and bone/joints ( due to longer period of anti TB drug)
    8. Pregnancy
    9. Patient choose to use efavirenz, not LPV/r. However, in ART naïve, EFV is allowed
    after intensive PK of LPV/r and rifabutin at week 2-4.

contacts and locations

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: NCT02415985

Locations

Thailand
Chest Division, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand, 10330
HIV-NAT, Thai Red Cross - AIDS Research Centre
Bangkok, Thailand, 10330
Infectious Diseases, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand, 10330
Bamrasnaradura Infectious Diseases Institute
Nonthaburi, Thailand, 11000

Sponsors and Collaborators

The HIV Netherlands Australia Thailand Research Collaboration
Bamrasnaradura Infectious Diseases Institute
Chulalongkorn University

Investigators

Principal Investigator: Anchalee Avihingsanon, MD, PhD HIV-NAT, Thai Red Cross - AIDS Research Centre
More Information

More Information

Additional Information:

HIV Netherlands Australia Thailand Research Collaboration

Responsible Party: The HIV Netherlands Australia Thailand Research Collaboration  
ClinicalTrials.gov Identifier: NCT02415985   History of Changes  
Other Study ID Numbers: HIV-NAT 116  
Study First Received: April 1, 2015  
Last Updated: February 11, 2020  

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:

pharmacokinetics of rifabutin
HIV/TB co-infection
resource limited setting
AUC
Cmax
Cmin
Ctrough

Additional relevant MeSH terms:
Tuberculosis
Lopinavir
Rifabutin

ClinicalTrials.gov processed this data on June 02, 2020
This information is provided by ClinicalTrials.gov.