Pharmacokinetics of the Tablet Formulation of Lopinavir/r as Standard and Increased Dosage During Pregnancy - Full Text View

Sponsor:	Oswaldo Cruz Foundation
Collaborator:	Ministery of Health, Brazil
Information provided by:	Oswaldo Cruz Foundation
ClinicalTrials.gov Identifier:	NCT00605098

Purpose

This is a multicenter, open, prospective and randomized study aimed at evaluating the pharmacokinetics of the tablet formulation of lopinavir/r administered in combination with two nucleoside analogs to HIV-infected pregnant women at two different dosages:

Group 1 (standard dosage): 200/50 mg lopinavir/r, 2 tablets every 12 hours, plus two nucleoside analogs.
Group 2 (increased dosage): 200/50 mg lopinavir/r, 2 tablets every 12 hours until the end of the second trimester of gestation (24 weeks) and 3 tablets every 12 hours in the third trimester (from 25 weeks on), plus two nucleoside analogs.

Treatment will be initiated at any time between 14 and 30 weeks of gestation and will be maintained for at least 6 weeks after delivery.

The objectives are:

To compare the pharmacokinetic parameters of the standard and increased dosage of the tablet formulation of lopinavir/r during pregnancy.
To determine whether the standard and/or increased dosage of the tablet formulation of lopinavir/r during pregnancy confers the same exposure to the drug as that observed in the same women after the end of pregnancy and in historic controls.
To evaluate the transplacental passage of lopinavir/r based on the ratio between the serum concentration in maternal blood at the time of delivery and in cord blood of the two drug dosages (standard and increased) administered during pregnancy.
To evaluate the tolerability of the two lopinavir/r dosages (standard and increased) during pregnancy.
To describe the vertical transmission rate of HIV to the children of the pregnant women included in the study.

Condition	Intervention	Phase
HIV Infections Pregnancy	Drug: Lopinavir / ritonavir Drug: Lopinavir/ritonavir	Phase IV

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Parallel Assignment, Pharmacokinetics Study
Official Title:	Pharmacokinetics of the Tablet Formulation of Lopinavir/r as Standard and Increased Dosage During Pregnancy in HIV-Infected Women

Resource links provided by NLM:

MedlinePlus related topics: AIDS AIDS and Pregnancy

Drug Information available for: Ritonavir Lopinavir

U.S. FDA Resources

Further study details as provided by Oswaldo Cruz Foundation:

Primary Outcome Measures:

Pharmacokinetic parameters of the tablet formulation of lopinavir/r [ Time Frame: Second and third pregnancy trimester and 6 weeks after delivery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Ratio between the serum concentration of lopinavir/r in maternal blood and in cord blood [ Time Frame: Delivery ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator	Drug: Lopinavir / ritonavir Lopinavir/r (200/50 mg, 2 tablets every 12 hours) plus two nucleoside analogs, starting at any time between 14 and 30 weeks of gestation and maintained for at least 6 weeks after delivery.
2: Experimental	Drug: Lopinavir/ritonavir Lopinavir/r (200/50 mg, 2 tablets every 12 hours) plus two nucleoside analogs, starting at any time between 14 and 30 weeks of gestation, increase the lopinavir/r dosage (200/50 mg, 3 tablets every 12 hours) in the third trimester (from 25 weeks on), and return to standard dose(200/50 mg, 2 tablets every 12 hours)for at least 6 weeks after delivery.

Eligibility

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

Criteria

Inclusion Criteria:

Capacity to consent and wish to participate in the study, documented by signing the specific informed consent form (ICF) of the study.
Age of 18 years or older.
Pregnancy documented by urine or blood examination or ultrasound.
Gestational age of 14 to 30 weeks calculated by ultrasound, obstetric examination or date of last menstruation, depending on what is considered to be more exact by the medical investigator.
HIV infection documented by two serological tests using different methods or analysis of HIV viral load with a positive result.
No use of antiretroviral drugs at the time of diagnosis of pregnancy (previous prophylaxis and treatment are allowed).
Intention to continue the treatment of the study for at least 6 weeks after delivery.

Exclusion Criteria:

History of hypersensitivity to lopinavir or ritonavir.
Need for the concomitant use of contraindicated drugs in combination with lopinavir/ritonavir.
Any condition that, in the opinion of the medical researchers, impairs the participation in and fulfillment of the procedures of the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00605098

Contacts

Contact: Marilia S Oliveira, MD	55 21 3865-9662	marilia.santini@ipec.fiocruz.br
Contact: Beatriz J Grinzstejn, MD	55 21 2270-7064	gbeatriz@ipec.fiocruz.br

Locations

Brazil
Hospital dos Servidores do Estado	Recruiting
Rio de Janeiro, Brazil, 20221903
Principal Investigator: Esau C Joao, MD
Brazil, Rio de Janeiro
Hospital Geral de Nova Iguaçu (HGNI)	Recruiting
Nova Iguaçu, Rio de Janeiro, Brazil, 26030-380
Principal Investigator: José Henrique S Pilotto, MD
Sub-Investigator: Jorge Eurico Ribeiro, MD
Brazil, RJ
Instituto de Pesquisa Clínica Evandro Chagas	Recruiting
Rio de Janeiro, RJ, Brazil, 21040-900
Contact: Valdiléa G Veloso-Santos, MD 55 21 3865-9550 valdilea.veloso@ipec.fiocruz.br
Principal Investigator: Marilia S Oliveira, MD
Principal Investigator: Beatriz J Grinsztejn, MD
Principal Investigator: Eduardo W Barroso, MD
Sub-Investigator: Luciana R Pitta, MSc
Sub-Investigator: Milton Ferreira Filho, PHd
Sub-Investigator: Marlice S Marques, PHd

Sponsors and Collaborators

Oswaldo Cruz Foundation

Ministery of Health, Brazil

Investigators

Principal Investigator:	Marilia S Oliveira, MD	IPEC - Oswaldo Cruz Foundation
Principal Investigator:	Beatriz J Grinsztejn, MD	IPEC - Oswaldo Cruz Foundation
Principal Investigator:	Eduardo W Barroso, MD	IPEC - Oswaldo Cruz Foundation
Principal Investigator:	Valdilea G Veloso-Santos, MD	IPEC - Oswaldo Cruz Foundation
Principal Investigator:	José Henrique S Pilotto, MD	Hospital Geral de Nova Iguaçu (HGNI)

More Information

No publications provided

Responsible Party:	Instituto de Pesquisa Clínica Evandro Chagas (IPEC) - Oswaldo Cruz Foundation ( Marilia Santini de Oliveira )
Study ID Numbers:	PK-LPV 01
Study First Received:	January 7, 2008
Last Updated:	June 18, 2009
ClinicalTrials.gov Identifier:	NCT00605098 History of Changes
Health Authority:	Brazil: National Committee of Ethics in Research

Keywords provided by Oswaldo Cruz Foundation:

HIV
Pregnancy
Vertical disease transmission
Pharmacokinetics
HIV seronegativity

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents

Pharmacologic Actions
Immunologic Deficiency Syndromes
Protease Inhibitors
Virus Diseases
Anti-Retroviral Agents
Lopinavir
HIV Infections
Ritonavir
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on February 08, 2010