Pharmacokinetics of Generic Lopinavir/Ritonavir in Pregnant Women

Study Overview
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Brief Summary
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To determine the pharmacokinetic profile of generic lopinavir/ritonavir tablets To investigate the possible influence of pregnancy and duration of pregnancy To determine the antiviral activity and safety of generic lopinavir/ritonavir® Compare pharmacokinetics parameters before and after pregnancy.

Detailed Description
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HAART in pregnant HIV-infected serves two goals, preventing mother to child transmission and providing adequate treatment for the mother. Levels of HIV RNA at delivery and the use of antiretrovirals (ARV) are independently associated with decreased transmission[1]. With a HAART regimen the transmission rate can be reduced till under the 2 %[1, 2]. Possibly suitable drugs which can be used during pregnancy is lopinavir/ritonavir based regimens. In Thailand, aluvir is not available therefore a generic lopinavir/ritonavir tablet formulation will be used in our study. In order to prove adequate levels of lopinavir/ritonavir, we will record 12-hour PK at third trimester. Second trimester and post-partum 12-hour PK are optional. Furthermore, we will collect safety and efficacy throughout the study.

Official Title
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The Pharmacokinetics and Safety of Generic Lopinavir/Ritonavir (200/50 mg Tablets) 400/100 mg q12h in Thai HIV-infected Pregnant Women

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: generic lopinavir/ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented positive test for HIV-1 infection Subject is at least 18 and not older than 40 years of age at the day of the first dosing of study medication Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. Pregnant for a maximum of 30 weeks at the day of first dosing of study medication Exclusion Criteria: History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients, which may be employed in the trial. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. Inability to understand the nature and extent of the trial and the procedures required. Abnormal serum transaminases or creatinine, determined as levels being > 3 times upper limit of normal. Concomitant use of medications that interfere with Generic lopinavir/ritonavir pharmacokinetics Active hepatobiliary or hepatic disease (N.B. chronic hepatitis B/C co-infection is allowed) Documented previous virological failure of a lopinavir/ritonavir containing regimen or documented resistance to lopinavir/ritonavir prior to dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>generic lopinavir/ritonavir | Drug: generic lopinavir/ritonavir<br>* Patients will start with lopinavir/ritonavir new formulation 400/100 mg bid with a low fat diet plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). The choice of the 2 NRTIs is at the discretion of the investigator, though in general the use of zidovudine+lamivudine (300/150mg Combivir®) is recommended. If patients can be included at or before gestational week 20, a 12h pharmacokinetic curve will be recorded at week 20 (± 2 weeks)(Group 1). There should be a minimum of 2 weeks between start of lopinavir and pharmacokinetic recording. If they are included after week 20, the first 12h pharmacokinetic curve will be recorded at gestational week 33 (± 2 weeks)(Group 2). For the patients in both groups a 12 hr curve will be recorded. Subjects in Group 1 will be offered to conduct a second 12h pharmacokinetic curve at week 20 (± 2 weeks), but this is only optional. Both groups will be asked to participate in the post partum curve, again this is optional.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the pharmacokinetic profile of generic lopinavir/ritonavir tablets 200/50 mg in pregnant Thai HIV-infected women |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the antiviral activity of generic lopinavir/ritonavir 400/100 mg BID in Thai pregnant women To determine the safety of generic lopinavir/ritonavir® 400/100 mg BID in Thai pregnant women Compare pharmacokinetics parameters before and after |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Generic lopinavir/ritonavir, Pharmacokinetics, Pregnancy, Antiviral activity, Safety