Clinical trial NCT00766818: The Effect of Pregnancy on the Pharmacokinetics of the Kaletra Tablet
Official title: The Effect of Pregnancy on the Pharmacokinetics of the Kaletra Tablet: A Longitudinal Investigation in the Second and Third Trimesters Including Empiric Dosage Adjustment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pregnancy
HIV
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2008-10-06
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 20-24 weeks, 30weeks, 32 weeks gestation and 8 weeks postpartum
measure: 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.
timeFrame: 20-24weeks, 30 weeks, 32 weeks gestation, 8weeks postpartum
Secondary outcomes:
measure: 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.
timeFrame: 20-24weeks, 30weeks, 32weeks gestation, 8 weeks postpartum
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Angela DM Kashuba, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina
name: Kristine B Patterson, MD
role: PRINCIPAL_INVESTIGATOR
References: