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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by University of Miami
Oswaldo Cruz Foundation
Information provided by (Responsible Party):
Catherine Boulanger, University of Miami Identifier:
First received: October 2, 2012
Last updated: June 4, 2015
Last verified: November 2014
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 Intervention Phase
Drug: Lopinavir/ritonavir and ritonavir
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:

Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Proportion of patients with expected pre dose concentration of lopinavir. [ Time Frame: Weeks 2 and 10-12: lopinavir time points at hours 0, 2, 4, 6 and 8. ] [ Designated as safety issue: Yes ]
    The expected pre dose concentration of lopinavir is >1.0 mcg/mL.

Secondary Outcome Measures:
  • Proportion of patients with successful treatment of HIV therapy. [ Time Frame: 10-12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Proportion of patients with expected AUC of rifampin [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]
    The expected AUC of rifampin is 44-70 mcg•h/mL

  • Proportion of patient with success of tuberculosis therapy [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]
    Success of treatment using criteria established by the Brazilian National Ttuberculosis Program.

  • Proportion of patients with expected Cmax and AUC of lopinavir [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]
    The expected Cmax of lopinavir is 6-14 mcg/mL. The expected AUC lopinavir is 56-130 µg•h/mL

  • Proportion of patients with expected Cmax of rifampin. [ Time Frame: Weeks 2 and 10-12: rifampin time points at hours 0, 2, 4, 6 and 8. ] [ Designated as safety issue: No ]
    Expected maximum concentration of rifampin is 8-24 mcg/mL

Estimated Enrollment: 12
Study Start Date: July 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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: Rifampin concentration sampling will be done. 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 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.


Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Be protease inhibitor naïve, defined as no prior PI use longer than 2 weeks.
  • 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.
  • HIV positive with documentation present in source document.
  • Have a CD4 cell count greater than 50 cells/mm3

Exclusion Criteria:

  • Non-compliance with DOT Plus.
  • History of being treated for tuberculosis in the prior 2 years unless there is DST 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01700790

Contact: Catherine V Boulanger, M.D. 305 243 4598
Contact: Valeria Calvacanti Rolla, M.D. 55 21 3869601

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   
Contact: Aline Benjamin, BSc, MSc    55 21 38659601   
Principal Investigator: Valeria Calvacanti Rolla, M.D.         
Sponsors and Collaborators
University of Miami
Oswaldo Cruz Foundation
Principal Investigator: Catherine Boulanger, MD. University of Miami Miller Medical School of Medicine
Principal Investigator: Valeria Calvicanti Rolla, MD Oswaldo Cruz Foundation
  More Information

Responsible Party: Catherine Boulanger, Associate of Professor of Clinical Medicine, University of Miami Identifier: NCT01700790     History of Changes
Other Study ID Numbers: 20100325
Study First Received: October 2, 2012
Last Updated: June 4, 2015
Health Authority: United States: Institutional Review Board
Brazil: Ethics Committee

Keywords provided by University of Miami:

Additional relevant MeSH terms:
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Anti-Bacterial Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antibiotics, Antitubercular
Antitubercular Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses processed this record on November 25, 2015