Pharmacokinetics of Generic Lopinavir/Ritonavir in Pregnant Women - Full Text View

Sponsored by:	The HIV Netherlands Australia Thailand Research Collaboration
Information provided by:	The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:	NCT00621166

Purpose

To determine the pharmacokinetic profile of generic lopinavir/ritonavir tablets To investigate the possible influence of pregnancy and duration of pregnancy To determine the antiviral activity and safety of generic lopinavir/ritonavir® Compare pharmacokinetics parameters before and after pregnancy.

Condition	Intervention	Phase
HIV Infections	Drug: generic lopinavir/ritonavir	Phase II

MedlinePlus related topics: AIDS AIDS and Pregnancy

Drug Information available for: Zidovudine Lamivudine Ritonavir Lopinavir Combivir

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Active Control, Single Group Assignment, Pharmacokinetics Study
Official Title:	The Pharmacokinetics and Safety of Generic Lopinavir/Ritonavir (200/50 mg Tablets) 400/100 mg q12h in Thai HIV-Infected Pregnant Women

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

Primary Outcome Measures:

To evaluate the pharmacokinetic profile of generic lopinavir/ritonavir tablets 200/50 mg in pregnant Thai HIV-infected women [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the antiviral activity of generic lopinavir/ritonavir 400/100 mg BID in Thai pregnant women To determine the safety of generic lopinavir/ritonavir® 400/100 mg BID in Thai pregnant women Compare pharmacokinetics parameters before and after [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	June 2008
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator generic lopinavir/ritonavir	Drug: generic lopinavir/ritonavir 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, though in general the use of zidovudine+lamivudine (300/150mg Combivir®) is recommended. If patients can be included at or before gestational week 20, a 12h pharmacokinetic curve will be recorded at week 20 (± 2 weeks)(Group 1). There should be a minimum of 2 weeks between start of lopinavir and pharmacokinetic recording. If they are included after week 20, the first 12h pharmacokinetic curve will be recorded at gestational week 33 (± 2 weeks)(Group 2). For the patients in both groups a 12 hr curve will be recorded. Subjects in Group 1 will be offered to conduct a second 12h pharmacokinetic curve at week 20 (± 2 weeks), but this is only optional. Both groups will be asked to participate in the post partum curve, again this is optional.

Arms

Assigned Interventions

1: Active Comparator

generic lopinavir/ritonavir

Drug: generic lopinavir/ritonavir

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, though in general the use of zidovudine+lamivudine (300/150mg Combivir®) is recommended. If patients can be included at or before gestational week 20, a 12h pharmacokinetic curve will be recorded at week 20 (± 2 weeks)(Group 1). There should be a minimum of 2 weeks between start of lopinavir and pharmacokinetic recording. If they are included after week 20, the first 12h pharmacokinetic curve will be recorded at gestational week 33 (± 2 weeks)(Group 2). For the patients in both groups a 12 hr curve will be recorded.

Subjects in Group 1 will be offered to conduct a second 12h pharmacokinetic curve at week 20 (± 2 weeks), but this is only optional. Both groups will be asked to participate in the post partum curve, again this is optional.

Detailed Description:

HAART in pregnant HIV-infected serves two goals, preventing mother to child transmission and providing adequate treatment for the mother. Levels of HIV RNA at delivery and the use of antiretrovirals (ARV) are independently associated with decreased transmission[1]. With a HAART regimen the transmission rate can be reduced till under the 2 %[1, 2]. Possibly suitable drugs which can be used during pregnancy is lopinavir/ritonavir based regimens. In Thailand, aluvir is not available therefore a generic lopinavir/ritonavir tablet formulation will be used in our study.

In order to prove adequate levels of lopinavir/ritonavir, we will record 12-hour PK at third trimester. Second trimester and post-partum 12-hour PK are optional. Furthermore, we will collect safety and efficacy throughout the study.

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Documented positive test for HIV-1 infection
Subject is at least 18 and not older than 40 years of age at the day of the first dosing of study medication
Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
Pregnant for a maximum of 30 weeks at the day of first dosing of study medication

Exclusion Criteria:

History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients, which may be employed in the trial.
Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
Inability to understand the nature and extent of the trial and the procedures required.
Abnormal serum transaminases or creatinine, determined as levels being > 3 times upper limit of normal.
Concomitant use of medications that interfere with Generic lopinavir/ritonavir pharmacokinetics
Active hepatobiliary or hepatic disease (N.B. chronic hepatitis B/C co-infection is allowed)
Documented previous virological failure of a lopinavir/ritonavir containing regimen or documented resistance to lopinavir/ritonavir prior to dosing

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621166

Contacts

Contact: Jasper v Lugt, MD	662-652-3040 ext 128	jasper.v@hivnat.org
Contact: Nittaya Phanuphak, MD	662-256-4107 ext 401	nittaya.p@chula.ac.th

Locations

Thailand
Department of Obsterics and Gynecology, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand, 10330

Sponsors and Collaborators

The HIV Netherlands Australia Thailand Research Collaboration

Investigators

Principal Investigator:

Surasith Chaithongwongwatthana, MD

Department of Obstetrics and Bynecology, Faculty of Medicine, Chulalongkorn University

More Information

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) This link exits the ClinicalTrials.gov site

Responsible Party:	Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University ( Associate Professor Surasith Chaithongwongwatthana )
Study ID Numbers:	HIV-NAT 093, approved
Study First Received:	February 12, 2008
Last Updated:	June 4, 2008
ClinicalTrials.gov Identifier:	NCT00621166
Health Authority:	Thailand: Ethical Committee

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:

Generic lopinavir/ritonavir
Pharmacokinetics
Pregnancy
Antiviral activity
Safety

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
Lopinavir
Ritonavir
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Lamivudine
Zidovudine
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
HIV Protease Inhibitors
Slow Virus Diseases
Anti-HIV Agents
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

Infection
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections

ClinicalTrials.gov processed this record on January 16, 2009