AIDSPhase 4NCT01700790
Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin
A Phase 4 study testing Lopinavir/ritonavir and ritonavir in people with AIDS and Tuberculosis, run by University of Miami at 1 site in Brazil.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- AIDS, Tuberculosis
- What is being tested?
- Lopinavir/ritonavir and ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteBrazil
- Study dates
- Feb 2016to 31 Dec 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
Show all 18Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Instituto Nacional de Infectologia Evandro Chagas - Fiocruz(INI), Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)
Rio de Janeiro, Rio de Janeiro, 21040-900
About this study
Official title: 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
Read the 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.
- Conditions
- AIDS, Tuberculosis
- Being tested
- Lopinavir/ritonavir and ritonavir
- Keywords
- HIV, AIDS, Tuberculosis, Rifampin, Lopinavir, Pharmacokinetic
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/ritonavir and ritonavirDrug
Also called Kaletra, Norvir
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
| Study group | Role | What they receive |
|---|---|---|
| Lopinavir/ritonavir and ritonavir | Experimental | 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. Receives: Drug: Lopinavir/ritonavir and ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with expected pre dose concentration of lopinavir.
The expected pre dose concentration of lopinavir is >1.0 mcg/mL.
Measured: Weeks 2 and 8: lopinavir time points at hours 0, 2, 4, 6 and 8.
Secondary outcomes (5)
Proportion of patients with successful treatment of HIV therapy.
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.
Measured: Approximately 10-12 weeks
Proportion of patients with expected AUC of rifampin
The expected AUC of rifampin is 44-70 mcg•h/mL
Measured: Approximatley 10-12 weeks
Proportion of patient with success of tuberculosis therapy
Success of treatment using criteria established by the Brazilian National Ttuberculosis Program.
Measured: Approximatly 10-12 weeks
Proportion of patients with expected Cmax and AUC of lopinavir
The expected Cmax of lopinavir is 6-14 mcg/mL. The expected AUC lopinavir is 56-130 µg•h/mL
Measured: 10-12 weeks
Proportion of patients with expected Cmax of rifampin.
Expected maximum concentration of rifampin is 8-24 mcg/mL
Measured: Weeks 2 and 8: rifampin time points at hours 0, 2, 4, 6 and 8.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startFeb 2016
- Primary completion17 Nov 2018
- Study completion31 Dec 2018
Why it stopped: No Further Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AIDSStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- Oswaldo Cruz Foundation
- Responsible party
- Principal investigator, Catherine Boulanger, University of Miami
- Investigators
- Catherine Boulanger, MD., Principal investigator, University of Miami Miller Medical School of MedicineValeria Calvicanti Rolla, MD, Principal investigator, Oswaldo Cruz Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01700790
- Sponsor's protocol ID
- 20100325
- Status last verified
- Dec 2018
- First submitted
- 2 Oct 2012
- Last updated
- 16 May 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Ren Y, Nuttall JJ, Egbers C, Eley BS, Meyers TM, Smith PJ, Maartens G, McIlleron HM. Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9. doi: 10.1097/QAI.0b013e3181642257.
PubMed 18197120la Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, Boeree MJ, Koopmans PP, Hekster YA, Burger DM. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004 May;48(5):1553-60. doi: 10.1128/AAC.48.5.1553-1560.2004.
PubMed 15105105Boulanger C, Rolla V, Al-Shaer MH, Peloquin C. Evaluation of super-boosted lopinavir/ritonavir in combination with rifampicin in HIV-1-infected patients with tuberculosis. Int J Antimicrob Agents. 2020 Feb;55(2):105840. doi: 10.1016/j.ijantimicag.2019.10.021. Epub 2019 Nov 5.
PubMed 31704214
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir in Combination With Rifampin in HIV-1-infected Patients With Tuberculosis.
- ClinicalTrials.gov ID
- NCT01700790
- Acronym / sponsor ID
- 20100325
- Conditions
- AIDS, Tuberculosis
- Keywords
- HIV, AIDS, Tuberculosis, Rifampin, Lopinavir, Pharmacokinetic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No Further Funding
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- Oswaldo Cruz Foundation
- Study start
- Feb 2016 (actual)
- Primary completion
- 17 Nov 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 4 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lopinavir/ritonavir and ritonavir | Experimental | Drug: Lopinavir/ritonavir and ritonavirTwo 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir/ritonavir and ritonavirAlso: Kaletra, NorvirTwo tablets twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 capsules of ritonavir 100 mg twice daily given with rifampin 600 mg daily | Drug | Lopinavir/ritonavir and ritonavir |
Primary outcome
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.
5 secondary outcomes
Proportion of patients with successful treatment of HIV therapy.
Time frame: Approximately 10-12 weeks
Proportion of patients with expected AUC of rifampin
Time frame: Approximatley 10-12 weeks
Proportion of patient with success of tuberculosis therapy
Time frame: Approximatly 10-12 weeks
Proportion of patients with expected Cmax and AUC of lopinavir
Time frame: 10-12 weeks
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.
Results and safety
The study was stopped early (reason given: No Further Funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2019.
- Background: PubMed 18197120Ren Y, Nuttall JJ, Egbers C, Eley BS, Meyers TM, Smith PJ, Maartens G, McIlleron HM. Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):566-9. doi: 10.1097/QAI.0b013e3181642257.
- Background: PubMed 15105105la Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, Boeree MJ, Koopmans PP, Hekster YA, Burger DM. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004 May;48(5):1553-60. doi: 10.1128/AAC.48.5.1553-1560.2004.
- Derived from this study: PubMed 31704214Boulanger C, Rolla V, Al-Shaer MH, Peloquin C. Evaluation of super-boosted lopinavir/ritonavir in combination with rifampicin in HIV-1-infected patients with tuberculosis. Int J Antimicrob Agents. 2020 Feb;55(2):105840. doi: 10.1016/j.ijantimicag.2019.10.021. Epub 2019 Nov 5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine Boulanger, MD. principal investigator
University of Miami Miller Medical School of Medicine
Valeria Calvicanti Rolla, MD principal investigator
Oswaldo Cruz Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lopinavir/ritonavir and ritonavir in people with AIDS and Tuberculosis, run by University of Miami at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: No Further Funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01700790, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2019.