The Effect of Pregnancy on the Pharmacokinetics of the Kaletra Tablet

The Effect of Pregnancy on the Pharmacokinetics of the Kaletra Tablet: A Longitudinal Investigation in the Second and Third Trimesters Including Empiric Dosage Adjustment

In this study, we are looking at blood concentrations of Kaletra in HIV positive patients during pregnancy. The patients will come in for 4 visits lasting ~24hrs. These visits take place at 20-24 weeks, 30 weeks, 32 weeks and 8 weeks post-partum. At the end of vist 2 (week 30), we will increase your dose to 2 adult Kaletra tablets, and one pediatric Kaletra tablet (total dose 500/125mg). The dose will remain increased until you are 2 weeks post partum, then it will return to the standard 2 adult tablets (400/100mg).

Study Overview

• Status: Completed
• Conditions: Pregnancy; HIV
• Intervention / Treatment: Drug: Kaletra

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• HIV positive
• Pregnant (<22 weeks)
• Currently taking or planning to start Kaletra
• ≥18 years of age

Exclusion Criteria:

• Active opportunistic or serious bacterial infection at the time of entry
• Past or present obstetrical complications (including, but not limited to: placentia previa, eclampsia, confirmed birth defects, multiple gestation pregnancies)
• Unable to maintain medication adherence, defined as ≥ 80% of doses taken between visits
• Currently receiving or expected to receive other protease inhibitors in conjunction with Kaletra®
• HIV genotype showing accumulation of protease inhibitor mutations expected to result in virologic failure on Kaletra® OR documented virologic failure on Kaletra®-containing regimen attributable to the Kaletra® component
• Chronic hepatitis B and/or C virus infection
• Cushing's Syndrome
• Untreated hypothyroidism or hyperthyroidism
• Serum Creatinine > 1.5 mg/dL
• Amylase 1.5 times ULN and/or abnormal lipase
• Direct or total bilirubin levels > Grade 1
• ALT/AST > Grade 2 (based on the NIH Division of AIDS (DAIDS) Table for Grading the Severity of Adverse Events
• Bicarbonate > Grade 2 (DAIDS)
• Hematology > Grade 2 (DAIDS), except for anemia: exclude only women with Hb< 9 g/dL and/or HCT , 27.3% (< 8.5 mg/dL and/or HCT , 25.6% if currently on ZDV) at screening; all subjects with anemia who enroll in the study must be receiving or start hematinics, including iron and folate supplements, immediately upon enrollment and continue until anemia resolves or end of pregnancy. The hematinic supplements may be discontinued at the discretion of the investigator if they consider continuation would not be in the best interest of the subject.
• Receiving the following drugs: astemizole, terfenadine, rifampin, cisapride, ergot derivatives, simvastatin, lovastatin, St. John's wort, pimozide, midazolam, triazolam, carbamezapine, phenobarbital, phenytoin, or dexamethasone

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Kaletra	Drug: Kaletra; Kaletra 400/100mg BID, then increase at 30weeks to 500/125mg BID; Other Names: lopinavir; ritonovir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare the C12h and AUC0-12h of protein bound and unbound blood plasma lopinavir (LPV) using standard doses during the second and third trimesters of pregnancy.	20-24 weeks, 30weeks, 32 weeks gestation and 8 weeks postpartum
To compare the C12h and AUC0-12h of protein bound and unbound blood plasma LPV between standard doses (400mg/100mg BID) and increased doses (500/125mg BID) of Kaletra® during the third trimester of pregnancy.	20-24weeks, 30 weeks, 32 weeks gestation, 8weeks postpartum

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare the C12h and AUC0-12h of protein bound and unbound blood plasma ritonavir (RTV) using standard doses during the second and third trimesters of pregnancy.	20-24weeks, 30weeks, 32weeks gestation, 8 weeks postpartum

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Kristine B Patterson, MD, University of North Carolina

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: October 3, 2008
• First Submitted That Met QC Criteria: October 3, 2008
• First Posted (Estimate): October 6, 2008

Study Record Updates

• Last Update Posted (Estimate): May 13, 2011
• Last Update Submitted That Met QC Criteria: May 11, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Lopinavir
• Other Study ID Numbers: IRB #06-0653