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

Phase 2

Completed

• Conditions: HIV; Tuberculosis
• Interventions: Drug: Lopinavir/r will be supplied by NHSO/GPO; Drug: Rifabutin

• Registration Number: NCT02415985
• Lead Sponsor: 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

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 Timeline

• Study First Submitted: 2015-04-01
• Study First Submitted QC: 2015-04-13
• Study First Posted: 2015-04-14
• Study Start: 2015-06
• Primary Completion: 2019-12
• Study Completion: 2019-12
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-11
• Last Update Posted: 2020-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rifabutin 150	Rifabutin	rifabutin 150 mg (1 capsule) once daily
rifabutin 150	Lopinavir/r will be supplied by NHSO/GPO	rifabutin 150 mg (1 capsule) once daily
rifabutin 300	Lopinavir/r will be supplied by NHSO/GPO	rifabutin 150 mg (2 capsules) 300 mg 3 times a week
rifabutin 300	Rifabutin	rifabutin 150 mg (2 capsules) 300 mg 3 times a week

Primary Outcome Measures

Name	Time	Method
pharmacokinetics of rifabutin Cmax	48 weeks	Cmax The peak plasma concentration of rifabutin after administration

Secondary Outcome Measures

Name	Time	Method
adverse events	48 weeks	number of participants with adverse events
viral load	48 weeks
CD4	48 weeks	mean CD4 rise from baseline
Monodrug resistant TB	48 weeks
death	48 weeks
AIDS event	48 weeks
TB cure	48 weeks
TB relapse	48 weeks
Multidrug-resistant TB (MDR TB)	48 weeks
TB treatment failure	48 weeks
Extensively drug resistant TB (XDR TB)	48 weeks
weight gain	48 weeks	change from baseline in weight gain at 48 weeks
defervescence	48 weeks	change from baseline in defervescence at 48 weeks
Karnofsky score	48 weeks	change from baseline in Karnofsky score at 48 weeks

Trial Locations

Locations (4)

Bamrasnaradura Infectious Diseases Institute; 🇹🇭 Nonthaburi, Thailand

HIV-NAT, Thai Red Cross - AIDS Research Centre; 🇹🇭 Bangkok, Thailand

Chest Division, Faculty of Medicine, Chulalongkorn University; 🇹🇭 Bangkok, Thailand

Infectious Diseases, Faculty of Medicine, Chulalongkorn University; 🇹🇭 Bangkok, Thailand