Back to resultsPharmacokinetics and Safety of Rifabutin 150 mg Once Daily Versus Rifabutin 300 mg Thrice Weekly
Primary Purpose
HIV, Tuberculosis
Status
Completed
Phase
Phase 2
Locations
Thailand
Study Type
Interventional
Intervention
Lopinavir/r will be supplied by NHSO/GPO
Rifabutin
Sponsored by
About this trial
This is an interventional other trial for HIV focused on measuring pharmacokinetics of rifabutin, HIV/TB co-infection, resource limited setting, AUC, Cmax, Cmin, Ctrough
Eligibility Criteria
Inclusion Criteria:
- Confirmed HIV positive after voluntary counseling and testing
- Aged >18-60years of age
- PI-naïve (NNRTI intolerance/failure) or PI experience ( TB developed during on salvage regimen) without prior PI mutation
- Any CD4 cell count
- ALT <5 times ULN
- Serum creatinine <1.4 mg/dl
- Hemaglobin >7 mg/L
- 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
- No other active OI (CDC class C event), except oral candidiasis or disseminated MAC
- Body weight >40kg
- Able to provide written informed consent
Exclusion Criteria:
- Current use of steroid (except short course steroid for IRIS) and other immunosuppressive agents.
- Current use of any prohibited medications related to drug pharmacokinetics.
- 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.
- Unlikely to be able to remain in follow-up for the protocol defined period.
- Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
- Karnofsky performance score <30%
- TB meningitis and bone/joints ( due to longer period of anti TB drug)
- Pregnancy
- 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.
Sites / Locations
- Chest Division, Faculty of Medicine, Chulalongkorn University
- HIV-NAT, Thai Red Cross - AIDS Research Centre
- Infectious Diseases, Faculty of Medicine, Chulalongkorn University
- Bamrasnaradura Infectious Diseases Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
rifabutin 150
rifabutin 300
Arm Description
rifabutin 150 mg (1 capsule) once daily
rifabutin 150 mg (2 capsules) 300 mg 3 times a week
Outcomes
Primary Outcome Measures
pharmacokinetics of rifabutin Cmax
Cmax The peak plasma concentration of rifabutin after administration
Secondary Outcome Measures
adverse events
number of participants with adverse events
viral load
CD4
mean CD4 rise from baseline
Monodrug resistant TB
death
AIDS event
TB cure
TB relapse
Multidrug-resistant TB (MDR TB)
TB treatment failure
Extensively drug resistant TB (XDR TB)
weight gain
change from baseline in weight gain at 48 weeks
defervescence
change from baseline in defervescence at 48 weeks
Karnofsky score
change from baseline in Karnofsky score at 48 weeks
Full Information
NCT ID
NCT02415985
First Posted
April 1, 2015
Last Updated
February 11, 2020
Sponsor
The HIV Netherlands Australia Thailand Research Collaboration
Collaborators
Bamrasnaradura Infectious Diseases Institute, Chulalongkorn University
1. Study Identification
Unique Protocol Identification Number
NCT02415985
Brief Title
Pharmacokinetics and Safety of Rifabutin 150 mg Once Daily Versus Rifabutin 300 mg Thrice Weekly
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 Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
June 2015 (Actual)
Primary Completion Date
December 2019 (Actual)
Study Completion Date
December 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The HIV Netherlands Australia Thailand Research Collaboration
Collaborators
Bamrasnaradura Infectious Diseases Institute, Chulalongkorn University
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV, Tuberculosis
Keywords
pharmacokinetics of rifabutin, HIV/TB co-infection, resource limited setting, AUC, Cmax, Cmin, Ctrough
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rifabutin 150
Arm Type
Other
Arm Description
rifabutin 150 mg (1 capsule) once daily
Arm Title
rifabutin 300
Arm Type
Other
Arm Description
rifabutin 150 mg (2 capsules) 300 mg 3 times a week
Intervention Type
Drug
Intervention Name(s)
Lopinavir/r will be supplied by NHSO/GPO
Other Intervention Name(s)
LPV/rtv
Intervention Description
200/50 mg tablet LPV/rtv
Intervention Type
Drug
Intervention Name(s)
Rifabutin
Primary Outcome Measure Information:
Title
pharmacokinetics of rifabutin Cmax
Description
Cmax The peak plasma concentration of rifabutin after administration
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
adverse events
Description
number of participants with adverse events
Time Frame
48 weeks
Title
viral load
Time Frame
48 weeks
Title
CD4
Description
mean CD4 rise from baseline
Time Frame
48 weeks
Title
Monodrug resistant TB
Time Frame
48 weeks
Title
death
Time Frame
48 weeks
Title
AIDS event
Time Frame
48 weeks
Title
TB cure
Time Frame
48 weeks
Title
TB relapse
Time Frame
48 weeks
Title
Multidrug-resistant TB (MDR TB)
Time Frame
48 weeks
Title
TB treatment failure
Time Frame
48 weeks
Title
Extensively drug resistant TB (XDR TB)
Time Frame
48 weeks
Title
weight gain
Description
change from baseline in weight gain at 48 weeks
Time Frame
48 weeks
Title
defervescence
Description
change from baseline in defervescence at 48 weeks
Time Frame
48 weeks
Title
Karnofsky score
Description
change from baseline in Karnofsky score at 48 weeks
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed HIV positive after voluntary counseling and testing
Aged >18-60years of age
PI-naïve (NNRTI intolerance/failure) or PI experience ( TB developed during on salvage regimen) without prior PI mutation
Any CD4 cell count
ALT <5 times ULN
Serum creatinine <1.4 mg/dl
Hemaglobin >7 mg/L
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
No other active OI (CDC class C event), except oral candidiasis or disseminated MAC
Body weight >40kg
Able to provide written informed consent
Exclusion Criteria:
Current use of steroid (except short course steroid for IRIS) and other immunosuppressive agents.
Current use of any prohibited medications related to drug pharmacokinetics.
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.
Unlikely to be able to remain in follow-up for the protocol defined period.
Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
Karnofsky performance score <30%
TB meningitis and bone/joints ( due to longer period of anti TB drug)
Pregnancy
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anchalee Avihingsanon, MD, PhD
Organizational Affiliation
HIV-NAT, Thai Red Cross - AIDS Research Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chest Division, Faculty of Medicine, Chulalongkorn University
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
HIV-NAT, Thai Red Cross - AIDS Research Centre
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Infectious Diseases, Faculty of Medicine, Chulalongkorn University
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Bamrasnaradura Infectious Diseases Institute
City
Nonthaburi
ZIP/Postal Code
11000
Country
Thailand
12. IPD Sharing Statement
Links:
URL
http://www.hivnat.org
Description
HIV Netherlands Australia Thailand Research Collaboration
Learn more about this trial
Pharmacokinetics and Safety of Rifabutin 150 mg Once Daily Versus Rifabutin 300 mg Thrice Weekly
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