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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by University of Miami
Sponsor:
Collaborator:
Oswaldo Cruz Foundation
Information provided by (Responsible Party):
Catherine Boulanger, University of Miami
ClinicalTrials.gov Identifier:
NCT01700790
First received: October 2, 2012
Last updated: June 9, 2016
Last verified: June 2016

October 2, 2012
June 9, 2016
January 2016
December 2017   (final data collection date for primary outcome measure)
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. ] [ Designated as safety issue: Yes ]
The expected pre dose concentration of lopinavir is >1.0 mcg/mL.
  • Proportion of patients with expected Cmax of rifampin. [ Time Frame: Weeks 1 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
  • 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.
Complete list of historical versions of study NCT01700790 on ClinicalTrials.gov Archive Site
  • Proportion of patients with successful treatment of HIV therapy. [ Time Frame: Approximately 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: Approximatley 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: Approximatly 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 8: 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
  • 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
Not Provided
Not Provided
 
Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin
A Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir in Combination With Rifampin in HIV-1-infected Patients With Tuberculosis.
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

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.

Interventional
Phase 4
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • AIDS
  • Tuberculosis
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
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.
Intervention: Drug: Lopinavir/ritonavir and ritonavir

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
12
March 2018
December 2017   (final data collection date for primary outcome measure)
  • 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.

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

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.
Both
18 Years to 65 Years   (Adult)
No
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
Brazil
 
NCT01700790
20100325
No
Undecided
Not Provided
Catherine Boulanger, University of Miami
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
University of Miami
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP