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:
University of Miami
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
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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 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.
Secondary Outcome Measures:
- 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
| Estimated Enrollment: | 12 |
| Study Start Date: | January 2016 |
| Estimated Study Completion Date: | March 2018 |
| Estimated Primary Completion Date: | December 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:
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years (Adult) |
| Genders Eligible for Study: | Both |
| 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.
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.
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
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@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: Aline Benjamin, BSc, MSc 55 21 38659601 aline.benjaminipec@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: | June 9, 2016 |
| Health Authority: | United States: Institutional Review Board Brazil: Ethics Committee |
| Individual Participant Data | |
| Plan to Share IPD: | Undecided |
Keywords provided by 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 |
ClinicalTrials.gov processed this record on September 27, 2016