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

Sponsor

The HIV Netherlands Australia Thailand Research Collaboration (Other)

Overall Status

Completed

CT.gov ID

NCT02415985

Collaborator

Bamrasnaradura Infectious Diseases Institute (Other), Chulalongkorn University (Other)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
HIV Tuberculosis	Drug: Lopinavir/r will be supplied by NHSO/GPO Drug: Rifabutin	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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

Actual Study Start Date :

Jun 1, 2015

Actual Primary Completion Date :

Dec 1, 2019

Actual Study Completion Date :

Dec 1, 2019

Arms and Interventions

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

Arm

Intervention/Treatment

Other: rifabutin 150

rifabutin 150 mg (1 capsule) once daily

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

200/50 mg tablet LPV/rtv

Other Names:

LPV/rtv

Drug: Rifabutin

Other: rifabutin 300

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

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

200/50 mg tablet LPV/rtv

Other Names:

LPV/rtv

Drug: Rifabutin

Outcome Measures

Primary Outcome Measures

pharmacokinetics of rifabutin Cmax [48 weeks]
Cmax The peak plasma concentration of rifabutin after administration

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed HIV positive after voluntary counseling and testing
Aged >18-60years of age
PI-naïve (NNRTI intolerance/failure) or PI experience ( TB developed during on salvage regimen) without prior PI mutation
Any CD4 cell count
ALT <5 times ULN
Serum creatinine <1.4 mg/dl
Hemaglobin >7 mg/L
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
No other active OI (CDC class C event), except oral candidiasis or disseminated MAC
Body weight >40kg
Able to provide written informed consent

Exclusion Criteria:

Current use of steroid (except short course steroid for IRIS) and other immunosuppressive agents.
Current use of any prohibited medications related to drug pharmacokinetics.
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.
Unlikely to be able to remain in follow-up for the protocol defined period.
Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
Karnofsky performance score <30%
TB meningitis and bone/joints ( due to longer period of anti TB drug)
Pregnancy
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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Chest Division, Faculty of Medicine, Chulalongkorn University	Bangkok	Thailand	10330
2	HIV-NAT, Thai Red Cross - AIDS Research Centre	Bangkok	Thailand	10330
3	Infectious Diseases, Faculty of Medicine, Chulalongkorn University	Bangkok	Thailand	10330
4	Bamrasnaradura Infectious Diseases Institute	Nonthaburi	Thailand	11000