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

NCT ID: NCT00605098

Last Updated: 2013-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2012-07-31

Brief Summary

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.

Conditions

HIV Infections; Pregnancy

Keywords

HIV; Pregnancy; Vertical disease transmission; Pharmacokinetics; HIV seronegativity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

Lopinavir / ritonavir

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Lopinavir/ritonavir

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Kaletra; Kaletra

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Brazil

OTHER_GOV

Sponsor Role: collaborator

Oswaldo Cruz Foundation

OTHER

Sponsor Role: lead

Responsible Party

Marilia Santini de Oliveira

Medical doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marilia S Oliveira, MD

Role: PRINCIPAL_INVESTIGATOR

IPEC - Oswaldo Cruz Foundation

Beatriz J Grinsztejn, MD

Role: PRINCIPAL_INVESTIGATOR

IPEC - Oswaldo Cruz Foundation

Eduardo W Barroso, MD

Role: PRINCIPAL_INVESTIGATOR

IPEC - Oswaldo Cruz Foundation

Valdilea G Veloso-Santos, MD

Role: PRINCIPAL_INVESTIGATOR

IPEC - Oswaldo Cruz Foundation

José Henrique S Pilotto, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Geral de Nova Iguaçu (HGNI)

Locations

Hospital Geral de Nova Iguaçu (HGNI)

Nova Iguaçu, Rio de Janeiro, Brazil

Hospital dos Servidores do Estado

Rio de Janeiro, Rio de Janeiro, Brazil

Instituto de Pesquisa Clínica Evandro Chagas

Rio de Janeiro, Rio de Janeiro, Brazil

Countries

Brazil

References

Santini-Oliveira M, Estrela Rde C, Veloso VG, Cattani VB, Yanavich C, Velasque L, Torres TS, Marins LM, Pilotto JH, Joao EC, Goncalves 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.

Reference Type: DERIVED

PMID: 24614377 (View on PubMed)

Other Identifiers

PK-LPV 01

Identifier Type: -

Identifier Source: org_study_id