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

The HIV Netherlands Australia Thailand Research Collaboration

Status and phase: Completed; Phase 2

Conditions: Tuberculosis; HIV

Treatments: Drug: Rifabutin; Drug: Lopinavir/r will be supplied by NHSO/GPO

Study type: Interventional

Funder types: Other

Identifiers

NCT02415985

HIV-NAT 116

Details and patient eligibility

About

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

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

rifabutin 150

Other group

Description:

rifabutin 150 mg (1 capsule) once daily

Treatment:

Drug: Rifabutin

Drug: Lopinavir/r will be supplied by NHSO/GPO

rifabutin 300

Other group

Description:

rifabutin 150 mg (2 capsules) 300 mg 3 times a week

Treatment:

Drug: Rifabutin

Drug: Lopinavir/r will be supplied by NHSO/GPO