TDM of Generic Lopinavir/Ritonavir 200/50 mg - Full Text View

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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Lopinavir

U.S. FDA Resources

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 ]


Enrollment:	70
Study Start Date:	January 2008
Study Completion Date:	December 2011
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: generic lopinavir/ritonavir 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 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 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

Arms

Assigned Interventions

Experimental: 1

Drug: generic lopinavir/ritonavir

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
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
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 (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Signed informed consent
Evidence of HIV infection (confirmed positive ELISA and/or documented history of measurable HIV RNA)
Age> 18 years
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
Currently having no AIDS defining illness
Willing to adhere to the protocol requirements

Exclusion Criteria:

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


Principal Investigator:	Anchalee Avihingsanon, MD, PhD	HIV-NAT, Thai Red Cross - AIDS Research Centre

More Information

Additional Information:

HIV-NAT's website This link exits the ClinicalTrials.gov site

Publications:

Ramautarsing RA, van der Lugt J, Gorowara M, Sophonphan J, Ananworanich J, Lange JM, Burger DM, Phanuphak P, Ruxthungtham K, Avihingsanon A. Pharmacokinetics and 48-week safety and efficacy of generic lopinavir/ritonavir in Thai HIV-infected patients. Antivir Ther. 2013;18(2):249-52. doi: 10.3851/IMP2324. Epub 2012 Aug 23.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

van der Lugt J, Lange J, Avihingsanon A, Ananworanich J, Sealoo S, Burger D, Gorowara M, Phanuphak P, Ruxrungtham K. Plasma concentrations of generic lopinavir/ritonavir in HIV type-1-infected individuals. Antivir Ther. 2009;14(7):1001-4. doi: 10.3851/IMP1410.


Responsible Party:	The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:	NCT00802334 History of Changes
Other Study ID Numbers:	HIV-NAT 095 IRB414/50
Study First Received:	May 29, 2008
Last Updated:	March 24, 2015
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:


Ritonavir Lopinavir 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

ClinicalTrials.gov processed this record on September 28, 2016