Evaluating the Safety and Pharmacokinetics of Raltegravir in Infants
NCT ID: NCT01828073
Last Updated: 2021-11-08
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
40 participants
OBSERVATIONAL
2011-05-19
2018-04-23
Brief Summary
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Detailed Description
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* Cohort 1 enrolled mother-infant pairs in which the infant was expected to be ≥2000 grams at birth (i.e. full term) at time of enrollment and the mother was living with HIV and received RAL 400 mg twice daily for at least 2 weeks prior to delivery and continued to receive antiretroviral (ARV) drugs during labor.
* Cohort 2 enrolled mother-infant pairs in which the infant was expected to be ≤2500 grams at birth \[i.e. low birth weight (LBW)\] at time of enrollment and the mother was living with HIV and received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery.
Cohorts 1 and 2 provided pharmacokinetics and safety data of in utero and intrapartum exposure to maternal RAL in full-term and LBW infants, respectively. Also, the study data were pooled with data from IMPAACT P1066 (NCT00485264) (Cohorts IV and V) and P1026s (NCT00042289) to determine the starting RAL dosing regimen for full-term and LBW infants in IMPAACT P1110 (NCT01780831).
The study initially opened accrual to Cohort 1 under protocol Version 1.0. Upon completion of accrual and follow-up of Cohort 1, the protocol was amended and accrual to and follow-up of Cohort 2 was under protocol Version 2.0.
No study-specific treatment was given to the participants during this study. The women (mothers) received RAL for clinical indications outside of the study. Infants received standard of care ARV therapy for prophylaxis of perinatal transmission of HIV as prescribed by their primary care physicians.
Cohort 1 mother-infant pairs were enrolled prior to delivery. The women were followed-up until discharge from the labor/delivery unit. Infants were followed from birth through 20 weeks after birth. If infant was eligible for PK sampling (see "Eligibility" section), blood samples were collected at 1-5, 8-14, 18-24, and 30-36 hours after birth. Protocol defined infant safety evaluations were at birth, and at 8-14 hours, 30-36 hours, 1 week and 20 weeks after birth.
Cohort 2 mother-infant pairs were enrolled prior to delivery or within 48 hours after delivery. The women were followed-up until discharge from the labor/delivery unit. Infants were followed from birth/entry through 6 weeks after birth. If infant was eligible for PK sampling, blood samples were collected at 1-6, 12-24, 36-48, 72-84, and 108-132 hours and 7-14 days after birth. Protocol defined infant safety evaluations were at entry/birth, and at 36-48 hours, 72-84 hours, 1 week and 6 weeks after birth.
For both cohorts, all infants regardless of whether they were eligible for PK sampling were included in the safety analyses. Infant safety data included adverse birth outcomes, signs/symptoms, diagnoses and chemistry/hematology test results. Protocol required chemistry tests were AST, ALT, serum creatinine, total bilirubin and direct bilirubin. Protocol required hematology tests were CBC with differential and platelet count. Also included in the safety data were additional laboratory events done outside of the study but considered by the site as relevant information.
For both cohorts, maternal blood and cord blood for RAL concentration testing were collected at delivery when specimen collection was possible. The optional genotypic testing (i.e. testing was done only if the mother consented) was limited to infants who were eligible for PK sampling. Information obtained about the effect of UGT1A1 polymorphisms on the PK of RAL was thought to provide a better understanding of the effect of genetics on the metabolism of RAL in neonates.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Cohort 1: Full term infants exposed in utero to maternal RAL
Infants, who were expected to be ≥2000 grams at birth (i.e. full-term) at time of enrollment, born to women with HIV-1 infection who received RAL 400 mg twice daily for at least two weeks prior to delivery and continued to receive ARVs during labor. The group also includes the mothers of these infants.
Raltegravir
No study-specific drugs were given to women or infants during this study. Women received RAL for clinical indications outside of the study.
Cohort 2: LBW infants exposed in utero to maternal RAL
Infants, who were expected to be ≤2500 grams at birth (i.e. LBW) at time of enrollment, born to women with HIV-1 infection who received at least one dose of RAL 400 mg within 2 to 24 hours prior to delivery. The group also includes the mothers of these infants.
Raltegravir
No study-specific drugs were given to women or infants during this study. Women received RAL for clinical indications outside of the study.
Interventions
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Raltegravir
No study-specific drugs were given to women or infants during this study. Women received RAL for clinical indications outside of the study.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Viable singleton pregnancy with gestational age of at least 35 weeks based on clinical or other obstetrical measurements with normal fetal anatomy
* Currently receiving RAL 400 mg twice daily for at least 2 weeks prior to enrollment in combination with other ARV agents for clinical care
* Plan to continue taking RAL in combination with other ARV agents through labor prior to delivery
* Willing and intends to deliver at the study-affiliated clinic or hospital
* Willing and able to sign informed consent for participation of herself and her infant. Participant must be of an age to provide legal informed consent as defined by the country in which she resides. If not, informed consent must be signed by a legal guardian.
* Infant born to women who received at least 2 weeks of RAL prior to delivery and continue to receive RAL during labor prior to delivery in addition to their other ARV drugs
* Infant birth weight of at least 2 kg
* Infant at least 37 weeks gestation at delivery
* Infant not receiving disallowed medications (phenobarbital, phenytoin, rifampin). If these medications are required for the infant's care, the infant will be ineligible for further PK sampling. PK samples will be obtained up to the time of the introduction of the disallowed medication.
* Documentation of HIV-1 infection.
* Viable singleton or multiple birth pregnancy based on clinical or other obstetrical measurements with infant birth weight anticipated to be less than or equal to 2,500 grams
* RAL is currently used as part of maternal ARV regimen and planned to continue through labor and delivery
* Willing and intends to deliver at the study-affiliated clinic or hospital
* Willing and able to sign informed consent for participation of herself and her infant. Participant must be of an age to provide legal informed consent as defined by the country in which she resides. If not, informed consent must be signed by a legal guardian.
* Documentation of HIV-1 infection.
* Received at least one dose of RAL within 2 to 24 hours prior to delivery
* Willing and able to sign informed consent for participation of herself and her infant. Participant must be of an age to provide legal informed consent as defined by the country in which she resides. If not, informed consent must be signed by a legal guardian.
* Infant birth weight less than or equal to 2,500 grams
* Infant less than or equal to 48 hours of age
Exclusion Criteria
\- Infant has a severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician
Cohort 2 enrolled M-I pairs at two time points: prior to delivery and within 48 hours after delivery.
* For M-I pairs enrolled prior to delivery, the maternal study eligibility criteria were assessed at enrollment. There were no infant study eligibility criteria. However, only infants who met the PK sampling eligibility criteria had PK blood sampling. Infants ineligible for PK sampling remained in the study and were followed-up for safety.
* For M-I pairs enrolled within 48 hours delivery, the maternal and infant study eligibility criteria were assessed at enrollment. A M-I pair was enrolled only if both the mother and the infant were eligible for the study. For multiple births, only infants who met the study eligibility criteria were enrolled.
\- Receipt of disallowed medications (phenobarbital, phenytoin, rifampin) within 4 weeks prior to enrollment or intent to be on any of the disallowed medications prior to delivery.
Cohort 2: Infant PK Blood Sampling Eligibility Criteria: M-I pairs enrolled prior to delivery
Infants were enrolled prior to delivery so there were no infant study eligibility criteria. Only infants who met the following criteria were eligible for PK blood sampling:
* Infant born to woman who received at least one dose of RAL within 2 to 24 hours prior to delivery. Dose administered to mother must have been at least 2 hours prior to delivery to allow time for adequate absorption and distribution.
* Infant birth weight less than or equal to 2,500 grams
* Infant not receiving disallowed medications (phenobarbital, phenytoin, rifampin) as described in the protocol. If these medications are required for the infant's care, the infant will be ineligible for further PK sampling. PK data will be obtained up to the time of the introduction of the disallowed medication.
* Infant less than or equal to 48 hours of age
* Infant does not have any severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician
\- Receipt of disallowed medications (phenobarbital, phenytoin, rifampin) within 4 weeks prior to delivery
* Received disallowed medications (phenobarbital, phenytoin, rifampin)
* Infant has a severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by the examining clinician
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Diana F. Clarke, PharmD
Role: STUDY_CHAIR
Boston Medical Center
Locations
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University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program
La Jolla, California, United States
Miller Children's Hosp. Long Beach CA NICHD CRS
Long Beach, California, United States
Usc La Nichd Crs
Los Angeles, California, United States
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, United States
Univ. of California San Francisco NICHD CRS
San Francisco, California, United States
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, United States
Boston Medical Center Ped. HIV Program NICHD CRS
Boston, Massachusetts, United States
Bronx-Lebanon Hospital Center NICHD CRS
The Bronx, New York, United States
Jacobi Med. Ctr. Bronx NICHD CRS
The Bronx, New York, United States
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, United States
Seattle Children's Research Institute CRS
Seattle, Washington, United States
Hospital Nossa Senhora da Conceicao NICHD CRS
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro, , Brazil
Hosp. Geral De Nova Igaucu Brazil NICHD CRS
Rio de Janeiro, , Brazil
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, , Brazil
Soweto IMPAACT CRS
Johannesburg, Gauteng, South Africa
Kilimanjaro Christian Medical Centre (KCMC)
Moshi, , Tanzania
Chiangrai Prachanukroh Hospital NICHD CRS
Chiang Mai, , Thailand
Countries
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References
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Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Merschman SA, Strohmaier KM, Ramael S, Lasseter KC, Stone JA, Gottesdiener KM, Wagner JA. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther. 2008 Feb;83(2):293-9. doi: 10.1038/sj.clpt.6100281. Epub 2007 Aug 22.
Wenning LA, Petry AS, Kost JT, Jin B, Breidinger SA, DeLepeleire I, Carlini EJ, Young S, Rushmore T, Wagner F, Lunde NM, Bieberdorf F, Greenberg H, Stone JA, Wagner JA, Iwamoto M. Pharmacokinetics of raltegravir in individuals with UGT1A1 polymorphisms. Clin Pharmacol Ther. 2009 Jun;85(6):623-7. doi: 10.1038/clpt.2009.12. Epub 2009 Mar 11.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, dated December 2004, Clarification August 2009
Other Identifiers
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11790
Identifier Type: REGISTRY
Identifier Source: secondary_id
IMPAACT P1097
Identifier Type: -
Identifier Source: secondary_id
P1097
Identifier Type: -
Identifier Source: org_study_id