Pharmacokinetics of the Tablet Formulation of Lopinavir/r as Standard and Increased Dosage During Pregnancy

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health, Brazil
Information provided by (Responsible Party):
Marilia Santini de Oliveira, Oswaldo Cruz Foundation
ClinicalTrials.gov Identifier:
NCT00605098
First received: January 7, 2008
Last updated: October 25, 2013
Last verified: October 2013
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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:


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 ]

Enrollment: 60
Study Start Date: February 2008
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 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.
Other Name: Kaletra
Experimental: 2 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.
Other Name: Kaletra

  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
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: NCT00605098

Locations
Brazil
Hospital Geral de Nova Iguaçu (HGNI)
Nova Iguaçu, Rio de Janeiro, Brazil, 26030-380
Instituto de Pesquisa Clínica Evandro Chagas
Rio de Janeiro, RJ, Brazil, 21040-900
Hospital dos Servidores do Estado
Rio de Janeiro, Brazil, 20221903
Sponsors and Collaborators
Oswaldo Cruz Foundation
Ministry 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 by Oswaldo Cruz Foundation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Marilia Santini de Oliveira, Medical doctor, Oswaldo Cruz Foundation
ClinicalTrials.gov Identifier: NCT00605098     History of Changes
Other Study ID Numbers: PK-LPV 01
Study First Received: January 7, 2008
Last Updated: October 25, 2013
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:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
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 October 23, 2014