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Pharmacokinetics (PK) and Safety of 2 Different Doses of Lopinavir/Ritonavir in in HIV/Tuberculosis (TB) Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy

Primary Purpose

HIV Infections, Tuberculosis

Status

Completed

Phase

Phase 2

Locations

Thailand

Study Type

Interventional

Intervention

LPV/r

About this trial

This is an interventional other trial for HIV Infections focused on measuring pharmacokinetics, safety, efficacy, Lopinavir/ritonavir, HIV/TB, rifampicin containing anti-tuberculosis therapy, Pharmacokinetics and safety of Lopinavir/ritonavir with rifampicin containing anti-tuberculosis therapy

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Confirmed HIV positive after voluntary counseling and testing
Aged >18-60years of age
ARV naïve and NNRTI failure ( PI naive)
CD4+ cell count of <350 cells/mm3 at the time of diagnosed TB
ALT <5 times ULN
Serum creatinine <1.4 mg/dl
Hemoglobin >8 mg/L
TB is diagnosed and planned to receive stable doses of rifampicin-containing anti-TB therapy for at least a 2 week period after initiation of ART
No other active OI (CDC class C event), except oral candidiasis or disseminated MAC
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%

Sites / Locations

HIV-NAT Thai Red Cross AIDS Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm Description

boosted LPV/r 400/100 mg BID + 2 NRTI

boosted LPV/r 600/150 mg BID + 2 NRTI

Outcomes

Primary Outcome Measures

plasma concentration level

Percentage of plasma concentration level above an acceptable lower limit (lopinavir Cmin > 1 mg/L) at steady-state.

Secondary Outcome Measures

identify toxicities

Toxicity of combined treatment for TB and HIV infections - the established DAIDS/ACTG toxicity grading scale of clinical and laboratory toxicities will be used.

CD4

CD4 response (mean CD4 rise from baseline)

HIV RNA

HIV RNA response (% < 50 copies/ml at week 12, 24 and 48)

genotypic resistant

The emergence of NRTI and/or lopinavir genotypic resistant and its clinically

Full Information

NCT ID

NCT01138202

First Posted

June 4, 2010

Last Updated

July 15, 2020

Sponsor

The HIV Netherlands Australia Thailand Research Collaboration

Collaborators

Department of Disease Control, Ministry of Public Health Thailand

1. Study Identification

Unique Protocol Identification Number

NCT01138202

Brief Title

Pharmacokinetics (PK) and Safety of 2 Different Doses of Lopinavir/Ritonavir in in HIV/Tuberculosis (TB) Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy

Official Title

A Pilot Study of the Pharmacokinetics and Safety of Lopinavir/Ritonavir 400/100mg Bid Versus Lopinavir/Ritonavir 600/150 mg BID Combined With Nucleoside Analogue Reverse Transcriptase Inhibitors in HIV/TB Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

November 2010 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The HIV Netherlands Australia Thailand Research Collaboration

Collaborators

Department of Disease Control, Ministry of Public Health Thailand

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

To assess safety, efficacy and impact of Lopinavir/ritonavir 400/100mg bid or Lopinavir/ritonavir 600/150mg bid in combination with rifampicin-containing anti-TB therapy.

Detailed Description

Fixed dose combination of d4T+3TC+NVP (GPOvir) is widely used in Thai HIV infected since June 2002. The prevalence of NNRTI resistance has increased since 2005. Tuberculosis can develop following NNRTI-based regimen failure or after introduction of a new salvage regimen with a boosted PI (immune recovery syndrome). Although, Efavirenz based HAART is preferred in TB/HIV with rifampicin containing antituberculosis. However, Efavirenz could not be used in case of NNRTI failure, intolerance or toxicity. It remains unknown how to optimally treat HIV /TB in populations in which rifampicin has to be used. Moreover, Rifabutin which is recommended when use concomitant with boosted PI4, 5, is not feasible in Thailand and other developing countries due to cost, toxicity and dosing considerations. If ritonavir-boosted LPV demonstrates suitable pharmacokinetics, and is well tolerated, this regimen might prove extremely useful and could be widely implemented. LPV/r is potent and widely available boosted PI in National Health System in Thailand. We therefore believe that there is a strong rationale and impetus for the study of LPV/r 400/100 mg bid versus LPV/r 600/150 mg bid as a boosted-PI combination that in the presence of RMP, is able to produce a satisfactory PK profile associated with adequate antiretroviral potency, tolerability and efficacy .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections, Tuberculosis

Keywords

pharmacokinetics, safety, efficacy, Lopinavir/ritonavir, HIV/TB, rifampicin containing anti-tuberculosis therapy, Pharmacokinetics and safety of Lopinavir/ritonavir with rifampicin containing anti-tuberculosis therapy

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

boosted LPV/r 400/100 mg BID + 2 NRTI

Arm Title

Arm Type

Experimental

Arm Description

boosted LPV/r 600/150 mg BID + 2 NRTI

Intervention Type

Drug

Intervention Name(s)

LPV/r

Intervention Description

LPV/r 400/100 mg BID + 2 NRTI for arm 1 (total 48 weeks) LPV/r 600/150 mg BID + 2 NRTI for arm 2 (total 48 weeks)

Primary Outcome Measure Information:

Title

plasma concentration level

Description

Percentage of plasma concentration level above an acceptable lower limit (lopinavir Cmin > 1 mg/L) at steady-state.

Time Frame

12 hours

Secondary Outcome Measure Information:

Title

identify toxicities

Description

Toxicity of combined treatment for TB and HIV infections - the established DAIDS/ACTG toxicity grading scale of clinical and laboratory toxicities will be used.

Time Frame

48 weeks

Title

CD4

Description

CD4 response (mean CD4 rise from baseline)

Time Frame

48 weeks

Title

HIV RNA

Description

HIV RNA response (% < 50 copies/ml at week 12, 24 and 48)

Time Frame

48 weeks

Title

genotypic resistant

Description

The emergence of NRTI and/or lopinavir genotypic resistant and its clinically

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Confirmed HIV positive after voluntary counseling and testing Aged >18-60years of age ARV naïve and NNRTI failure ( PI naive) CD4+ cell count of <350 cells/mm3 at the time of diagnosed TB ALT <5 times ULN Serum creatinine <1.4 mg/dl Hemoglobin >8 mg/L TB is diagnosed and planned to receive stable doses of rifampicin-containing anti-TB therapy for at least a 2 week period after initiation of ART No other active OI (CDC class C event), except oral candidiasis or disseminated MAC 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%

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anchalee Avihingsanon, MD

Organizational Affiliation

The HIV Netherlands Australia Thailand Research Collaboration

Official's Role

Principal Investigator

Facility Information:

Facility Name

HIV-NAT Thai Red Cross AIDS Research Center

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

12. IPD Sharing Statement

Links:

URL

http://www.hivnat.org

Description

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Learn more about this trial

Pharmacokinetics (PK) and Safety of 2 Different Doses of Lopinavir/Ritonavir in in HIV/Tuberculosis (TB) Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy

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