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Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin

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ClinicalTrials.gov Identifier: NCT01700790
Recruitment Status : Recruiting
First Posted : October 4, 2012
Last Update Posted : November 7, 2017
Sponsor:
Collaborator:
Oswaldo Cruz Foundation
Information provided by (Responsible Party):
Catherine Boulanger, University of Miami

Study Description
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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

Condition or disease Intervention/treatment Phase
AIDS Tuberculosis Drug: Lopinavir/ritonavir and ritonavir Phase 4

Detailed Description:

This will be an open label non-randomized pharmacokinetic study of 10-12 HIV-infected patients co-infected with Mycobacterium tuberculosis.

Enrollment: Potential subjects with active tuberculosis who have tolerated a rifampin containing regimen for at least 2 weeks. Potential subjects will be referred from the surrounding communities to Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)

Visit 1: Subjects will then be started on lopinavir/ritonavir containing HAART regimen with standard twice daily dosing. Ritonavir 100 mg capsules will be added to the regimen and the dose escalated until the patient is taking 3 capsules twice daily. The time between enrollment and visit 1 will be determined by the treating physician.

Visit 2: They will return about 1 week after dose escalation has been completed to sample lopinavir and rifampin concentrations.

Visit 3: Subject will return in 2 weeks to have repeat to review results of lopinavir concentrations and response to therapy. Ritonavir will be adjusted as needed.

Visit 4: Subject will then return in 4 weeks for last visit for evaluation. Lopinavir and rifampin PK will be done.


Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir in Combination With Rifampin in HIV-1-infected Patients With Tuberculosis.
Actual Study Start Date : February 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2019

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U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Lopinavir/ritonavir and ritonavir
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
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
Other Names:
  • Kaletra
  • Norvir


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of patients with expected pre dose concentration of lopinavir. [ Time Frame: Weeks 2 and 8: lopinavir time points at hours 0, 2, 4, 6 and 8. ]
    The expected pre dose concentration of lopinavir is >1.0 mcg/mL.


Secondary Outcome Measures :
  1. Proportion of patients with successful treatment of HIV therapy. [ Time Frame: Approximately 10-12 weeks ]
    HIV failure will be defined as failure to drop the viral load by 0.5 log 10 copies/mL drop by week 4 of treatment and a viral load drop >1 log 10 copies/ml by week 8.

  2. Proportion of patients with expected AUC of rifampin [ Time Frame: Approximatley 10-12 weeks ]
    The expected AUC of rifampin is 44-70 mcg•h/mL

  3. Proportion of patient with success of tuberculosis therapy [ Time Frame: Approximatly 10-12 weeks ]
    Success of treatment using criteria established by the Brazilian National Ttuberculosis Program.

  4. Proportion of patients with expected Cmax and AUC of lopinavir [ Time Frame: 10-12 weeks ]
    The expected Cmax of lopinavir is 6-14 mcg/mL. The expected AUC lopinavir is 56-130 µg•h/mL

  5. Proportion of patients with expected Cmax of rifampin. [ Time Frame: Weeks 2 and 8: rifampin time points at hours 0, 2, 4, 6 and 8. ]
    Expected maximum concentration of rifampin is 8-24 mcg/mL


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Antiretroviral naive

  • If not antiretroviral naïve they must meet the following criteria:

    • Taking Kaletra containing regimen with suppressed viral load.
    • Taking an NNRTI or integrase containing regimen without prior history of use of PI for more than 2 weeks
    • Taking an NNRTI or integrase containing regimen with prior exposure to PI greater than 2 weeks. It must be clearly stated in the source document that PI was switched to another agent for convenience.
    • Taking another PI containing regimens with suppressed viral load. It must be clearly stated in source document that if another PI was used for greater than 2 weeks the regimen was switched to another agent for convenience. Subjects with prior history of PI use may be enrolled, if there is a genotype showing no resistance to Kaletra Other Inclusion criteria
  • 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.

Exclusion Criteria:

  • 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.
  • Have a CD4 cell count of 50 cells/mm3or less
  • Hepatitis B or C infection
  • Alcohol or illicit drug use, which in the investigators opinion may affect participation in study.
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01700790


Contacts
Contact: Catherine V Boulanger, M.D. 305 243 4598 cboulang@med.miami.edu
Contact: Valeria Calvacanti Rolla, M.D. 55 21 3869601 valeria.rolla@ini.fiocruz.br

Locations
Brazil
Instituto Nacional de Infectologia Evandro Chagas - Fiocruz(INI), Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB) Recruiting
Rio de Janeiro, RJ, Brazil, 21040-900
Contact: Valeria Calvacanti Rolla, MD    55 21 38659601    valeria.rolla@gmail.com   
Contact: Isabella Campos Vargas de Morais, BSc, MSc    55 21 981090208    Isabella Moraes <isabellacvmoraes@gmail.com>   
Principal Investigator: Valeria Calvacanti Rolla, M.D.         
Sponsors and Collaborators
University of Miami
Oswaldo Cruz Foundation
Investigators
Principal Investigator: Catherine Boulanger, MD. University of Miami Miller Medical School of Medicine
Principal Investigator: Valeria Calvicanti Rolla, MD Oswaldo Cruz Foundation
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Responsible Party: Catherine Boulanger, Associate of Professor of Clinical Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT01700790     History of Changes
Other Study ID Numbers: 20100325
First Posted: October 4, 2012    Key Record Dates
Last Update Posted: November 7, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Catherine Boulanger, University of Miami:
HIV
AIDS
Tuberculosis
 Rifampin
Lopinavir
Pharmacokinetic

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Ritonavir
Lopinavir
Rifampin
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
 Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers