Trial record 15 of 30 for:    " October 02, 2012":" November 01, 2012"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 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: July 3, 2014
Last verified: July 2014
  Purpose

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
AIDS
Tuberculosis
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 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.


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


Estimated Enrollment: 12
Study Start Date: July 2014
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (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: After enrollment the subject will have a baseline rifampin PK will be done. They 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.

  Eligibility

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

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 tuberculosis 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 DOTPlus.
  • 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/mm3 or 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 ClinicalTrials.gov identifier: 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@ipec.fiocruz.br

Locations
Brazil
Instituto de Pesquisa Clinica Evandro Chagas (IPEC), Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB) Not yet recruiting
Rio de Janeiro, RJ, Brazil, 21040-900
Contact: Valeria Calvacanti Rolla, MD    55 21 38659601    valeria.rolla@ipec.fiocruz.br   
Contact: Rafeala Silverio, BSc, MSc    55 21 38659601    RafealaSilverio.IPEC@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

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
Study First Received: October 2, 2012
Last Updated: July 3, 2014
Health Authority: United States: Institutional Review Board
Brazil: Ethics Committee

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

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Rifampin
Ritonavir
Lopinavir
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
HIV Protease Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014