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

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 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Pharmacokinetics and Safety of Generic Lopinavir/Ritonavir (200/50 mg Tablets) 400/100 mg q12h in Thai HIV-infected Pregnant Women

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 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 ]


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

Arms	Assigned Interventions
Active Comparator: 1 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

Active Comparator: 1

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 (Adult)
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

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: NCT00621166

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

Additional Information:

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


Responsible Party:	The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:	NCT00621166 History of Changes
Other Study ID Numbers:	HIV-NAT 093 approved
Study First Received:	February 12, 2008
Last Updated:	April 3, 2012
Health Authority:	Thailand: Ethical Committee

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:


Generic lopinavir/ritonavir Pharmacokinetics Pregnancy Antiviral activity Safety

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases 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 23, 2016