Clinical trial NCT02415985: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
Tuberculosis
Keywords: pharmacokinetics of rifabutin
HIV/TB co-infection
resource limited setting
AUC
Cmax
Cmin
Ctrough
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Bamrasnaradura Infectious Diseases Institute
name: Chulalongkorn University
First posted: 2015-04-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility 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.

Primary outcomes:
measure: pharmacokinetics of rifabutin Cmax
timeFrame: 48 weeks
Secondary outcomes:
measure: adverse events
timeFrame: 48 weeks
measure: viral load
timeFrame: 48 weeks
measure: CD4
timeFrame: 48 weeks
measure: Monodrug resistant TB
timeFrame: 48 weeks
measure: death
timeFrame: 48 weeks
measure: AIDS event
timeFrame: 48 weeks
measure: TB cure
timeFrame: 48 weeks
measure: TB relapse
timeFrame: 48 weeks
measure: Multidrug-resistant TB (MDR TB)
timeFrame: 48 weeks
measure: TB treatment failure
timeFrame: 48 weeks
measure: Extensively drug resistant TB (XDR TB)
timeFrame: 48 weeks
measure: weight gain
timeFrame: 48 weeks
measure: defervescence
timeFrame: 48 weeks
measure: Karnofsky score
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Chest Division, Faculty of Medicine, Chulalongkorn University
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross - AIDS Research Centre
city: Bangkok
country: Thailand
facility: Infectious Diseases, Faculty of Medicine, Chulalongkorn University
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Infectious Diseases Institute
Study officials:
affiliation: HIV-NAT, Thai Red Cross - AIDS Research Centre
name: Anchalee Avihingsanon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: