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

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

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

Study Overview

• Status: Completed
• Conditions: HIV; Tuberculosis
• Intervention / Treatment: Drug: Rifabutin; Drug: Lopinavir/r will be supplied by NHSO/GPO

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Chest Division, Faculty of Medicine, Chulalongkorn University
  • Bangkok, Thailand, 10330
    • HIV-NAT, Thai Red Cross - AIDS Research Centre
  • Bangkok, Thailand, 10330
    • Infectious Diseases, Faculty of Medicine, Chulalongkorn University
  • Nonthaburi, Thailand, 11000
    • Bamrasnaradura Infectious Diseases Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: rifabutin 150; rifabutin 150 mg (1 capsule) once daily	Drug: Rifabutin; Drug: Lopinavir/r will be supplied by NHSO/GPO; 200/50 mg tablet LPV/rtv; Other Names: LPV/rtv
OTHER: rifabutin 300; rifabutin 150 mg (2 capsules) 300 mg 3 times a week	Drug: Rifabutin; Drug: Lopinavir/r will be supplied by NHSO/GPO; 200/50 mg tablet LPV/rtv; Other Names: LPV/rtv

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacokinetics of rifabutin Cmax	Cmax The peak plasma concentration of rifabutin after administration	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	number of participants with adverse events	48 weeks
viral load		48 weeks
CD4	mean CD4 rise from baseline	48 weeks
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	change from baseline in weight gain at 48 weeks	48 weeks
defervescence	change from baseline in defervescence at 48 weeks	48 weeks
Karnofsky score	change from baseline in Karnofsky score at 48 weeks	48 weeks

Collaborators and Investigators

• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration
• Collaborators: Chulalongkorn University; Bamrasnaradura Infectious Diseases Institute

Publications and helpful links

Helpful Links

• HIV Netherlands Australia Thailand Research Collaboration

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2015
• Primary Completion (ACTUAL): December 1, 2019
• Study Completion (ACTUAL): December 1, 2019

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: April 13, 2015
• First Posted (ESTIMATE): April 14, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: AUC; Cmax; resource limited setting; pharmacokinetics of rifabutin; HIV/TB co-infection; Cmin; Ctrough
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Lopinavir; Rifabutin
• Other Study ID Numbers: HIV-NAT 116