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

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ClinicalTrials.gov Identifier: NCT02415985
Recruitment Status : Recruiting
First Posted : April 14, 2015
Last Update Posted : August 10, 2017
Sponsor:
Collaborators:
Bamrasnaradura Infectious Diseases Institute
Chulalongkorn University
Information provided by (Responsible Party):
The HIV Netherlands Australia Thailand Research Collaboration

Brief Summary:
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 or disease Intervention/treatment Phase
HIV Tuberculosis Drug: Lopinavir/r will be supplied by NHSO/GPO Drug: Rifabutin Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
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
Study Start Date : June 2015
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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
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



Primary Outcome Measures :
  1. pharmacokinetics of rifabutin Cmax [ Time Frame: 48 weeks ]
    Cmax The peak plasma concentration of rifabutin after administration


Secondary Outcome Measures :
  1. adverse events [ Time Frame: 48 weeks ]
    number of participants with adverse events

  2. viral load [ Time Frame: 48 weeks ]
  3. CD4 [ Time Frame: 48 weeks ]
    mean CD4 rise from baseline

  4. Monodrug resistant TB [ Time Frame: 48 weeks ]
  5. death [ Time Frame: 48 weeks ]
  6. AIDS event [ Time Frame: 48 weeks ]
  7. TB cure [ Time Frame: 48 weeks ]
  8. TB relapse [ Time Frame: 48 weeks ]
  9. Multidrug-resistant TB (MDR TB) [ Time Frame: 48 weeks ]
  10. TB treatment failure [ Time Frame: 48 weeks ]
  11. Extensively drug resistant TB (XDR TB) [ Time Frame: 48 weeks ]
  12. weight gain [ Time Frame: 48 weeks ]
    change from baseline in weight gain at 48 weeks

  13. defervescence [ Time Frame: 48 weeks ]
    change from baseline in defervescence at 48 weeks

  14. Karnofsky score [ Time Frame: 48 weeks ]
    change from baseline in Karnofsky score at 48 weeks



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02415985


Contacts
Contact: Anchalee Avihingsanon, MD, PhD 662 652 3040 anchalee.a@hivnat.org

Locations
Thailand
Chest Division, Faculty of Medicine, Chulalongkorn University Recruiting
Bangkok, Thailand, 10330
Contact: Kamol Kawkitinarong, MD       kamonkaw@hotmail.com   
Sub-Investigator: Kamol Kawkitinarong, MD         
HIV-NAT, Thai Red Cross - AIDS Research Centre Recruiting
Bangkok, Thailand, 10330
Contact: Anchalee Avihingsanon, MD, PhD    662 652 3040    anchalee.a@hivnat.org   
Principal Investigator: Anchalee Avihingsanon, MD, PhD         
Infectious Diseases, Faculty of Medicine, Chulalongkorn University Recruiting
Bangkok, Thailand, 10330
Contact: Kamolwan Jutivorakool, MD         
Contact: Gompol Suwanpimolkul, MD         
Sub-Investigator: Opass Putcharoen, MD         
Sub-Investigator: Kamolwan Jutivorakool, MD         
Sub-Investigator: Gompol Suwanpimolkul, MD         
Bamrasnaradura Infectious Diseases Institute Recruiting
Nonthaburi, Thailand, 11000
Contact: Weerawat Manosuthi, MD       drweerawat@hotmail.com   
Sub-Investigator: Weerawat Manosuthi, MD         
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

Additional Information:
Responsible Party: The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier: NCT02415985     History of Changes
Other Study ID Numbers: HIV-NAT 116
First Posted: April 14, 2015    Key Record Dates
Last Update Posted: August 10, 2017
Last Verified: August 2017

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
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lopinavir
Rifabutin
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents
Antibiotics, Antitubercular
Antitubercular Agents