NCT01700790

Brief Summary

The object of this study is to evaluate the pharmacokinetic interactions, short term safety and efficacy of standard dose lopinavir/ritonavir 200mg/50 (two tablets twice daily) given with ritonavir 100 mg three tablets twice daily given in combination with rifampin in HIV-infected persons with tuberculosis

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Feb 2016

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 2, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 4, 2012

Completed
3.3 years until next milestone

Study Start

First participant enrolled

February 1, 2016

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 17, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2018

Completed
Last Updated

May 16, 2019

Status Verified

December 1, 2018

Enrollment Period

2.8 years

First QC Date

October 2, 2012

Last Update Submit

May 14, 2019

Conditions

AIDSTuberculosis

Keywords

HIVAIDSTuberculosisRifampinLopinavirPharmacokinetic

Outcome Measures

Primary Outcomes (1)

  • Proportion of patients with expected pre dose concentration of lopinavir.

    The expected pre dose concentration of lopinavir is \>1.0 mcg/mL.

    Weeks 2 and 8: lopinavir time points at hours 0, 2, 4, 6 and 8.

Secondary Outcomes (5)

  • Proportion of patients with successful treatment of HIV therapy.

    Approximately 10-12 weeks

  • Proportion of patients with expected AUC of rifampin

    Approximatley 10-12 weeks

  • Proportion of patient with success of tuberculosis therapy

    Approximatly 10-12 weeks

  • Proportion of patients with expected Cmax and AUC of lopinavir

    10-12 weeks

  • Proportion of patients with expected Cmax of rifampin.

    Weeks 2 and 8: rifampin time points at hours 0, 2, 4, 6 and 8.

Study Arms (1)

Lopinavir/ritonavir and ritonavir

EXPERIMENTAL

Two tablets of twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 tablets of ritonavir 100 mg of twice daily given with rifampin 600 mg daily.

Drug: Lopinavir/ritonavir and ritonavir

Interventions

Lopinavir/ritonavir and ritonavirDRUG

Two tablets twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 capsules of ritonavir 100 mg twice daily given with rifampin 600 mg daily

Also known as: Kaletra, Norvir
Lopinavir/ritonavir and ritonavir

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Be at least 18 years of age and able to give informed consent.
  • Diagnosed with TB by criteria per Brazilian Ministry of Health
  • Have a good clinical response to TB.
  • Tolerating tuberculosis therapy containing rifampin for the 2 weeks prior to screening,except for persons taking protease inhibitors at time of diagnosis of TB.,. Subjects taking protease inhibitors will be screened and initiate visit 1 within 3 days of starting TB medication
  • HIV positive with documentation present in source document.
  • Have a CD4 cell count greater than 50 cells/mm3if not taking ART. Persons with cd4 \< 50 may be enrolled, if it is felt that in the best interest of the patient, that enrollment in the study will allow for quicker initiation of antiretroviral therapy than referral to another treatment center.

You may not qualify if:

  • Non-compliance with DOTPlus. Alternatively DOT can be done by telephoning patient on a daily basis 5 times a week and having patient annotate taking drug in a log which would be reviewed by clinic staff
  • History of being treated for tuberculosis in the prior 2 years unless there is DST, including PCR testing, showing sensitivity to rifamycin.
  • Known hypersensitivity to rifampin or rifabutin.
  • Liver enzymes greater than 2 times ULN.
  • Bilirubin greater than 2 times ULN.
  • Serum creatinine greater than 3 times ULN.
  • Hemoglobin less than 7.0 gms even if receiving erythropoietin.
  • Absolute neutrophil count less than 750 cells/mm3 even if receiving G-CSF.
  • Fasting triglycerides greater than 400 mg/dL.
  • Fasting cholesterol \> 1.6 upper limits of normal.
  • GI intolerance of tuberculosis medications requiring discontinuation of tuberculosis medications.
  • Fasting glucose greater 150 mg/dL.
  • Pregnant women.
  • Use of one of the prohibited medications
  • Any condition that the investigators feel could compromise the use of the current medication.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Instituto Nacional de Infectologia Evandro Chagas - Fiocruz(INI), Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)

Rio de Janeiro, Rio de Janeiro, 21040-900, Brazil

Location

Related Publications (3)

  • Ren Y, Nuttall JJ, Egbers C, Eley BS, Meyers TM, Smith PJ, Maartens G, McIlleron HM. Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9. doi: 10.1097/QAI.0b013e3181642257.

    PMID: 18197120BACKGROUND

  • la Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, Boeree MJ, Koopmans PP, Hekster YA, Burger DM. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004 May;48(5):1553-60. doi: 10.1128/AAC.48.5.1553-1560.2004.

    PMID: 15105105BACKGROUND

  • Boulanger C, Rolla V, Al-Shaer MH, Peloquin C. Evaluation of super-boosted lopinavir/ritonavir in combination with rifampicin in HIV-1-infected patients with tuberculosis. Int J Antimicrob Agents. 2020 Feb;55(2):105840. doi: 10.1016/j.ijantimicag.2019.10.021. Epub 2019 Nov 5.

    PMID: 31704214DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency SyndromeTuberculosis

Interventions

lopinavir-ritonavir drug combinationRitonavir

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Catherine Boulanger, MD.

    University of Miami Miller Medical School of Medicine

    PRINCIPAL INVESTIGATOR

  • Valeria Calvicanti Rolla, MD

    Oswaldo Cruz Foundation

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate of Professor of Clinical Medicine

Study Record Dates

First Submitted

October 2, 2012

First Posted

October 4, 2012

Study Start

February 1, 2016

Primary Completion

November 17, 2018

Study Completion

December 31, 2018

Last Updated

May 16, 2019

Record last verified: 2018-12

Data Sharing

IPD Sharing
Will not share

Locations

BR(1)