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

January 7, 2008
October 25, 2013
February 2008
July 2012   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00605098 on ClinicalTrials.gov Archive Site
Ratio between the serum concentration of lopinavir/r in maternal blood and in cord blood [ Time Frame: Delivery ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Pharmacokinetics of the Tablet Formulation of Lopinavir/r as Standard and Increased Dosage During Pregnancy
Pharmacokinetics of the Tablet Formulation of Lopinavir/r as Standard and Increased Dosage During Pregnancy in HIV-infected Women

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.
Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • HIV Infections
  • Pregnancy
  • 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
  • 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
  • Active Comparator: 1
    Intervention: Drug: Lopinavir / ritonavir
  • Experimental: 2
    Intervention: Drug: Lopinavir/ritonavir
Santini-Oliveira M, Estrela Rde C, Veloso VG, Cattani VB, Yanavich C, Velasque L, Torres TS, Marins LM, Pilotto JH, João EC, Gonçalves JC, Grinsztejn B. Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in HIV-positive pregnant women. Antimicrob Agents Chemother. 2014 May;58(5):2884-93. doi: 10.1128/AAC.02599-13. Epub 2014 Mar 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
July 2012
July 2012   (final data collection date for primary outcome measure)

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.
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Brazil
 
NCT00605098
PK-LPV 01
No
Marilia Santini de Oliveira, Oswaldo Cruz Foundation
Oswaldo Cruz Foundation
Ministry of Health, Brazil
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)
Oswaldo Cruz Foundation
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP