Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

TDM of Generic Lopinavir/Ritonavir 200/50 mg

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by The HIV Netherlands Australia Thailand Research Collaboration.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
The Government Pharmaceutical Organization
Information provided by:
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT00802334
First received: May 29, 2008
Last updated: November 30, 2010
Last verified: November 2010
  Purpose

Evaluating the bioavailibility safety and efficacy of the generic LPV/RTV 200/50 mg tablet formulation in a 400/100 mg BID dose in Thai HIV infected individuals.


Condition Intervention Phase
HIV
Drug: generic lopinavir/ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Therapeutic Drug Monitoring of the Generic Lopinavir/Ritonavir Tablets 200/50 mg in the Thai HIV-infected Patient

Resource links provided by NLM:


Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures:
  • To determine the Cmin levels of the generic lopinavir/ritonavir tablets 200/50 mg in Thai HIV-infected patients [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess 48 weeks safety and tolerability of the generic lopinavir tablets 200/50 mg for the standard dosing regimen [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: January 2008
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: generic lopinavir/ritonavir
  1. Screening visit

    • Clinical and safety laboratory assessment. Viral load for patients on a PI-based regimen, if a VL results ≤ 3 months is not available

  2. Baseline visit

    • (Within 30 days after screening) Baseline clinical and laboratory assessment, patients who were on a Kaletra SGC formulation before baseline will undergo TDM. Start generic lopinavir/ritonavir tablets 200/50 in a 400/100mg bid dosage. Backbone will be chosen on the discretion of the study physician

  3. Week 4

    • Steady state TDM lopinavir and ritonavir, at 10-12 hr after the last intake (Cmin)

Clinical, safety and laboratory assessment

Week 12: Clinical, safety and efficacy laboratory assessment Week 24: Clinical, safety and efficacy laboratory assessment Week 48: Clinical, safety and efficacy laboratory assessment


Detailed Description:

The original solid oral formulation of lopinavir/ritonavir was a soft gel capsule (SGC) in a 133/33 mg formulation. This formulation requires refrigerated storage and need to be administered with food[4]. Recently Abbott developed a new formulation of this fixed combination, a 200/50 mg tablet (Aluvia). This formulation showed to be bioequivalence to the old formulation, don't need refrigerated storage and has diminished food effect[5].

This are profound advantages for the developing world, but till now Aluvia is not available in Thailand yet, and if it will, the price might be an issue for most of the HIV-infected Thai patients.

The Indian company Matrix has produced the generic formulation of Abbott's Aluvia. In Indian healthy volunteers this tablet formulation has proven to be bioequivalent to Abbott's Aluvia in a 400/100 mg bid dosing (unpublished data). Implementing this drug in Thai clinical practice will save a huge amount of costs and, as a result, will make the second line regimen more accessible for the Thai HIV-infected population. We expect that the BE data from the Indian population can be extrapolated to the Thai population, but to confirm this and in order to register this drug in Thailand an extensive therapeutic drug monitoring (TDM) of 100 patients has to be done. To meet these regulatory criteria HIVNAT will coordinate and assess a TDM trial in Thai HIV-infected patients who are eligible for using the generic 200/50 mg lopinavir/ritonavir tablets 200/50 mg.

This is open-label, single-center phase-II trial in 100 HIV-infected subjects. Patients can be either treatment-naïve or treatment-experienced when entering this clinical trial. After meeting the in- and exclusion criteria, patients will start with lopinavir/ritonavir new formulation 400/100 mg bid with a low fat diet, plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). The choice of the 2 NRTIs is at the discretion of the investigator. Only patient who are on Kaletra SGC will undergo TDM sampling at baseline. Although the paper of Klein et al. showed diminished food effect[5] we still will advice our patient to take it with food, until more data on the generic product becomes available, confirming the lack of food effect on the pharmacokinetics.

Once patients are included a (generic) lopinavir/ritonavir based regimen will be designed and initiated. Patients who were on a Kaletra SGC based regimen before baseline will undergo TDM at base line. Therapeutic drug monitoring of lopinavir will be done after 4 weeks, to ensure steady state. At baseline and week 4 safety data will be obtained.

After the first 30 patients showed good bioavailibility, the other 70 subjects will be followed up for total of 48 weeks to obtain safety and efficacy data

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent
  2. Evidence of HIV infection (confirmed positive ELISA and/or documented history of measurable HIV RNA)
  3. Age> 18 years
  4. On a standard PI containing HAART regimen with 2 NRTIs with a VL < 50 copies for at least 12 weeks OR ARV-naive patients, or patient on a NNRTI based regimen
  5. Currently having no AIDS defining illness
  6. Willing to adhere to the protocol requirements

Exclusion Criteria:

  1. Any history of taking CYP450 inhibitors or inducers, or any gastric acid-reducing drugs within 14 days of enrollment in the study
  2. Current pregnancy or lactating
  3. Active opportunistic infection
  4. ALT/ AST more than 2 x upper limit
  5. creatinine more than 1.5 time the upper limit
  6. Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion
  7. History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients which may be employed in the study.
  8. Active drug abuse
  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: NCT00802334

Locations
Thailand
HIV-NAT
Bangkok, Thailand, 10330
Sponsors and Collaborators
The HIV Netherlands Australia Thailand Research Collaboration
The Government Pharmaceutical Organization
Investigators
Study Chair: Reshmie Ramautarsing, MD The HIV Netherlands Australia Thailand Research Collaboration
  More Information

Additional Information:
No publications provided by The HIV Netherlands Australia Thailand Research Collaboration

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Professor Kiat Ruxrungtham, HIV-NAT
ClinicalTrials.gov Identifier: NCT00802334     History of Changes
Other Study ID Numbers: HIV-NAT 095, IRB414/50
Study First Received: May 29, 2008
Last Updated: November 30, 2010
Health Authority: Thailand: Ethical Committee

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:
generic lopinavir/ritonavir
therapeutic drug monitoring
safety and efficacy

Additional relevant MeSH terms:
Lopinavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014