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

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02415985
• Other study ID #: HIV-NAT 116
• Status: Completed
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: December 2019

Study information

• Verified date: February 2020
• Source: The HIV Netherlands Australia Thailand Research Collaboration
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV
• Tuberculosis

Intervention

Drug:
• Lopinavir/r will be supplied by NHSO/GPO
200/50 mg tablet LPV/rtv
• Rifabutin

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
The HIV Netherlands Australia Thailand Research Collaboration	Bamrasnaradura Infectious Diseases Institute, Chulalongkorn University

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pharmacokinetics of rifabutin Cmax	Cmax The peak plasma concentration of rifabutin after administration	48 weeks
Secondary	adverse events	number of participants with adverse events	48 weeks
Secondary	viral load		48 weeks
Secondary	CD4	mean CD4 rise from baseline	48 weeks
Secondary	Monodrug resistant TB		48 weeks
Secondary	death		48 weeks
Secondary	AIDS event		48 weeks
Secondary	TB cure		48 weeks
Secondary	TB relapse		48 weeks
Secondary	Multidrug-resistant TB (MDR TB)		48 weeks
Secondary	TB treatment failure		48 weeks
Secondary	Extensively drug resistant TB (XDR TB)		48 weeks
Secondary	weight gain	change from baseline in weight gain at 48 weeks	48 weeks
Secondary	defervescence	change from baseline in defervescence at 48 weeks	48 weeks
Secondary	Karnofsky score	change from baseline in Karnofsky score at 48 weeks	48 weeks

External Links

•   HIV Netherlands Australia Thailand Research Collaboration