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| ID | Type | Description | Link |
|---|---|---|---|
| 11891 | Registry Identifier | DAIDS ES | |
| IMPAACT P1110 |
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The purpose of this study was to evaluate the safety and pharmacokinetics (PK) of raltegravir (RAL) when given to HIV-1-exposed, normal birth weight newborn infants at risk of acquiring HIV-1 infection. (PK is the study of the time course of absorption, distribution, metabolism, and excretion of drugs in the body.) The primary goal of this study was to determine a dose of RAL that was safe and met the PK targets for infants when administered during the first 6 weeks of life in addition to standard of care antiretroviral (ARV) agents for prevention of perinatal transmission.
This is a Phase I multi-center, open label, non-comparative study to evaluate the safety and PK of RAL administered to HIV-1-exposed full-term (≥37 weeks of gestation) infants when administered during the first 6 weeks of life in addition to the infants' standard HIV-1 ARV prophylaxis.
IMPAACT P1097 (NCT01828073) demonstrated that RAL crossed the placenta from mother to fetus after maternal dosing during pregnancy and RAL was slowly eliminated by the newborn after birth. Therefore, for P1110, within each cohort, infants were stratified into the "RAL-naive" or "RAL-exposed" groups depending on infants' in utero exposure to maternal RAL. The study stratification with respect to in utero RAL exposure allowed for adjustment of the initial RAL dosing (i.e. timing and/or dose size).
Study participants were enrolled in two sequential cohorts with the following actual dosing of RAL in addition to their local standard of care ARV agents for prevention of perinatal transmission. PK and safety data from Cohort 1 (two single doses) provided information for the starting dosing for Cohort 2 (daily dosing through 6 weeks of life).
Cohort 1: Two single RAL doses: first dose within 48 hours of birth and second dose at 7-10 days of life.
Cohort 2: Daily RAL dosing through 6 weeks of life.
Target enrollment was approximately 50 infants and their mothers in order to have a minimum of 12 and 20 PK evaluable infants in Cohorts 1 and 2, respectively. Cohort 1 and Cohort 2 RAL-naive infants (and their mothers) were enrolled under protocol Version 1.0. Cohort 2 RAL-exposed infants (and their mothers) were enrolled under protocol Version 2.0.
Infants and their mothers were enrolled within 48 and within 60 hours of delivery under protocol Versions 1.0 and 2.0, respectively. Infants were followed through 24 weeks of life and their mothers were followed until discharge from the labor and delivery unit.
Infant PK samples were collected as follows:
Cohort 1:
Cohort 2:
Protocol defined infant safety evaluations were done at:
Cohort 1: Entry, 3-4 days of life, 7-10 days of life, 2 weeks of life, 6 weeks of life and 24 weeks of life.
Cohort 2: Entry, 2-4 days of life, 6-9 days of life, 15-18 days of life, 28-32 days of life, 5-6 weeks of life, 8-10 weeks of life and 24 weeks of life.
Infant safety data included death, signs/symptoms, diagnoses and laboratory test results. Laboratory test results included results from evaluations specified in the protocol and evaluations done as part of the infant's clinical care which the sites considered relevant.
PK evaluable infants were those determined by the protocol pharmacologist to have PK results which provide analyzable data on the primary PK parameters of interest. Infants who were PK unevaluable were replaced for PK analysis but continued with the study safety follow-up visits.
Infants were evaluable for safety analysis if they received at least one dose of RAL. The safety analyses were based on data from all safety evaluable infants, regardless of whether they were evaluable for PK analysis.
The study initially opened accrual to Cohort 1 RAL-naive group. The PK and safety data from IMPAACT P1110 Cohort 1 RAL-naive group and from IMPAACT P1097 were used to determine the starting dose for the Cohort 1 RAL-exposed group. Opening accrual to the Cohort 2 RAL-naive group was contingent upon infants enrolled in Cohort 1 RAL-naive and RAL-exposed groups successfully meeting safety criteria and providing adequate PK data to determine a regimen to be tested for daily dosing through 6 weeks of life for the Cohort 2 RAL-naive group. The initial dosing regimen for the Cohort 2 RAL-naive group was determined using population PK modeling and simulations incorporating IMPAACT P1110 Cohort 1 data, along with data from the following IMPAACT studies: P1097, P1066 (NCT00485264) (Cohorts IV and V) and P1026s (NCT00042289). Since the PK results of Cohort 1 RAL-naive and exposed groups were similar except in the first 1-2 days of life and P1097 Cohort 1 results suggested that maternal RAL readily crosses the placenta and results to washout RAL exposure in neonates, Cohort 2 RAL-exposed group was determined to receive the same dose of RAL as Cohort 2 RAL-naive group, except the initial dose for RAL-exposed was delayed to within 12 to 60 hours of life.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | HIV-1-exposed full-term infants. Infants received two single doses of RAL: first dose within 48 hours of birth and second dose at 7-10 days of life:
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| Cohort 2 | Experimental | HIV-1-exposed full-term infants. Daily RAL through 6 weeks of life with first dosing within 48 hours of birth and between 12-60 hours of birth for in utero RAL-naive and RAL-exposed infants, respectively. Daily RAL through 6 weeks of life: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Raltegravir | Drug | RAL was given as oral granules for suspension. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Infants Who Died or Had Grade 3/4 Adverse Event Through 6 Weeks of Life | Number of infants who died or had adverse events (AEs) of Grade 3 or 4 as defined in DAIDS AE Grading Table. Events with onset dates prior to first RAL dosing and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs. | From first dosing of RAL through 6 weeks of life |
| AUC24 for Cohort 1 RAL Dose #1 (Within 48 Hours of Birth) | Area Under the Concentration-time Curve at 24-hour interval (AUC24) based on intensive PK sampling around Cohort 1 RAL dose #1 (within 48 hours of birth) | Cohort 1 RAL dose #1 (within 48 hours of birth) intensive PK sampling: within 30 min pre-dose; and 1-2, 4-8, 12 (±1), 24 (±1) hours post-dose. |
| Cmax for Cohort 1 RAL Dose #1 (Within 48 Hours of Birth) | Maximum concentration (Cmax) for Cohort 1 dose #1 (within 48 hours of birth) | Cohort 1 dose #1(within 48 hours of birth) intensive PK sampling: within 30 min pre-dose; and 1-2, 4-8, 12 (±1), 24 (±1) hours post-dose. |
| AUC24 for Cohort 2 Initial RAL Dose (Within 48 and 12-60 Hours of Birth for RAL-naive and RAL-exposed Groups, Respectively) | Area Under the Concentration-time Curve at the 24-hour interval (AUC24) for Cohort 2 initial RAL dose (within 48 and between 12-60 hours of birth for RAL-naive and RAL-exposed, respectively). | Cohort 2 initial dose (within 48 and between 12-60 hours of birth for RAL-naive and RAL-exposed, respectively) intensive PK sampling: within 1 hour pre-dose; and 1-2, 6-10, 20-24 hours post-dose. |
| Clast for Cohort 2 Initial RAL Dose (Within 48 and Between 12-60 Hours of Birth for RAL-naïve and RAL-exposed Groups, Respectively) | Last concentration of the drug (Clast) at 24 hour interval post dosing for the Cohort 2 initial RAL dose (within 48 and at 12-60 hours of birth for RAL-naive and RAL-exposed, respectively). This is the plasma RAL concentration from a sample collected at or close to 24 hours post dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Infants Who Died or Had Grade 3/4 Adverse Event Through 24 Weeks of Life | Number of infants who died or had adverse events (AEs) of Grade 3 or 4 as defined in DAIDS AE Grading Table. Events with onset dates prior to first RAL dosing and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs. | From first RAL dose through 24 weeks of life |
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Maternal Inclusion Criteria:
Mother is living with HIV and either i) known to have HIV diagnosis prior to labor (testing obtained and designated per local SOC in the medical record and either on or recently started CART prior to delivery) or ii) identified as having HIV diagnosis at the time of labor or in the immediate postpartum period. More information on this criterion can be found in the protocol.
Risk of mothers transmitting HIV to their infants:
Maternal written informed consent for study participation
Maternal Exclusion Criteria:
Known maternal-fetal blood group incompatibility as evidenced by the presence of an unexpected clinically significant maternal red cell antibody that is known to be capable of causing hemolytic disease of the fetus/newborn
Mother will be receiving RAL as part of her combination antiretroviral (cART) regimen after delivery and intending to breastfeed her infant
For Cohort 1 and Cohort 2 RAL-naive groups:
Infant Inclusion Criteria:
Age at enrollment (Note: The full-term infants were HIV-exposed and may have received standard of care ARV prophylaxis/treatment before enrollment):
Infant gestational age at birth at least 37 weeks
No known 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
Birth weight at least 2 kg
Able to take oral medications
Parent or legal guardian able and willing to provide signed informed consent
For Cohort 1 and Cohort 2 RAL-exposed groups:
Infant Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Diana F. Clarke, PharmD | Section of Pediatric Infectious Diseases, Boston Medical Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Usc La Nichd Crs | Los Angeles | California | 90089 | United States | ||
| Children's National Med. Ctr. Washington DC NICHD CRS |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22716975 | Background | Nielsen-Saines K, Watts DH, Veloso VG, Bryson YJ, Joao EC, Pilotto JH, Gray G, Theron G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Ceriotto M, Machado D, Bethel J, Morgado MG, Dickover R, Camarca M, Mirochnick M, Siberry G, Grinsztejn B, Moreira RI, Bastos FI, Xu J, Moye J, Mofenson LM; NICHD HPTN 040/PACTG 1043 Protocol Team. Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. N Engl J Med. 2012 Jun 21;366(25):2368-79. doi: 10.1056/NEJMoa1108275. |
| Label | URL |
|---|---|
| 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 | View source |
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Cohort 1 participants were from 2 sites in Brazil, 1 site in South Africa and 7 sites in the USA. Enrollment period was January 2014 - December 2015.
Cohort 2 participants were from 3 sites in Brazil, 2 sites in South Africa,1 site in Thailand, and 4 sites in the USA. Enrollment period was September 2015 - November 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single doses of RAL: first dose (3 mg/kg or 2mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 18, 2017 | Apr 23, 2020 |
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| Cohort 2 initial dose (within 48 and between 12-60 hours of birth for RAL-naive and RAL-exposed groups, respectively) intensive PK sampling: within 1 hour pre-dose; and 1-2, 6-10, 20-24 hours post-dose. |
| RAL AUC12 for Cohort 2 at 15-18 Days of Life | Area Under the Concentration-time Curve at 12-hour interval (AUC12) of RAL for Cohort 2 at 15-18 days of life. | Intensive PK sampling for Cohort 2 at 15-18 days of life: within 1 hour pre-dose; and 1-2, 4-6, 8-12 hours post-dose. |
| RAL C12 for Cohort 2 at 15-18 Days of Life | RAL concentration at 12 hours (C12) for Cohort 2 at 15-18 days of life. | Intensive PK sampling for Cohort 2 at 15-18 days of life: within 1 hour pre-dose; and 1-2, 4-6, 8-12 hours post-dose. |
| Number of Infants Who Died or Had SADR of Grade 3 or 4 Through 6 Weeks of Life | Number of infants who died or had Suspected Adverse Drug Reaction (SADR) of Grade 3 or 4 as defined in DAIDS AE Grading Table. Events with onset dates prior to the first RAL dosing and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs. SADRs are AEs assessed as definitely related, probably related or possibly related to RAL. | From first RAL dose through 6 weeks of life |
| Number of Infants Who Died or Had SADR of Grade 3 or 4 Through 24 Weeks of Life | Number of infants who died or had Suspected Adverse Drug Reaction (SADR) of Grade 3 or 4 as defined in DAIDS AE Grading Table. Events with onset dates prior to the first RAL dosing and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs. SADRs are AEs assessed as definitely related, probably related or possibly related to RAL. | From first RAL dose through 24 weeks of life |
| Cohort 1 Dose #1 Neonatal RAL Elimination (CL/F) by UGT1A1 Genotype Group | Cohort 1 Dose #1 neonatal RAL elimination was represented by Clearance (CL/F), which is the volume of plasma cleared of the drug per unit time. Genotyping for polymorphisms of UGT1A1 were performed on infants who were eligible for PK sampling and were consented by their mothers/guardians (i.e. genotyping was optional) . | Cohort 1 Dose #1 Intensive PK sampling: within 30 min pre-dose; and 1-2, 4-8, 12, 24 hours post-dose. Samples for UGT1A1 genotype testing were collected at study entry. |
| Cohort 2 Initial Dose Neonatal RAL Elimination (CL/F) by UGT1A1 Genotype Group | Cohort 2 initial dose neonatal RAL elimination was represented by Clearance (CL/F), which is defined as the volume of plasma cleared of the drug per unit time. Genotyping for polymorphisms of UGT1A1 were performed on infants who were eligible for PK sampling and were consented by their mothers/guardians (i.e. genotyping was optional) . | Intensive PK sampling for Cohort 2 initial dose: within 1 hour pre-dose; and 1-2, 6-10, 20-24 hours post-dose. Samples for UGT1A1 genotype testing were collected at study entry. |
| Cohort 2 Neonatal RAL Elimination (CL/F) at 15-18 Days of Life by UGT1A1 Genotype Group | Cohort 2 15-18 days of life dose neonatal RAL elimination was represented by Clearance (CL/F), which is defined as the volume of plasma cleared of the drug per unit time at 15-18 days of life when RAL dosing would have been 3 mg/kg twice daily. Genotyping for polymorphisms of UGT1A1 were performed on infants who were eligible for PK sampling and were consented by their mothers/guardians(i.e. genotyping was optional) . | Intensive PK sampling for Cohort 2 at 15-18 days of life: within 1 hour pre-dose; and 1-2 hours post-dose, 4-6, 8-12 hours post-dose. Samples for UGT1A1 genotype testing were collected at study entry. |
| Number of Cohort 1 Infants With Hyperbilirubinemia by UGT1A1 Genotype | Hyperbilirubinemia was defined as total bilirubin exceeding 16.0 mg/dL or receipt of phototherapy, or transfusion therapy, or other therapies for hyperbilirubinemia or elevated bilirubin. | Specimens for bilirubin testing were collected at study entry; Days 3-4, 7-10 of life; and Weeks 2, 6, 24 of life for Cohort 1. Specimen for genotype testing was collected at entry. |
| Number of Cohort 2 Infants With Hyperbilirubinemia by UGT1A1 Genotype | Hyperbilirubinemia was defined as total bilirubin exceeding 16.0 mg/dL or receipt of phototherapy, or transfusion therapy, or other therapies for hyperbilirubinemia or elevated bilirubin. | Specimens for bilirubin testing were collected at study entry; after 2nd dose; Days 6-9, 15-18, 28-32 of life; and Weeks 5-6, 8-10, 24 of life for Cohort 2. Specimen for genotype testing was collected at study entry. |
| Number of Cohort 1 Infants With Hyperbilirubinemia by SLCO1B3 Genotype | Hyperbilirubinemia was defined as total bilirubin exceeding 16.0 mg/dL or receipt of phototherapy, or transfusion therapy, or other therapies for hyperbilirubinemia or elevated bilirubin. | Specimens for bilirubin test were collected at study entry; Days 3-4, 7-10 of life; and Weeks 2, 6, 24 of life for Cohort 1. Specimen for genotype testing was collected at study entry. |
| Number of Cohort 2 Infants With Hyperbilirubinemia by SLCO1B3 Genotype | Hyperbilirubinemia was defined as total bilirubin exceeding 16.0 mg/dL or receipt of phototherapy, or transfusion therapy, or other therapies for hyperbilirubinemia or elevated bilirubin. | Specimens for bilirubin testing were collected at study entry; after 2nd dose; Days 6-9, 15-18, 28-32 of life; and Weeks 5-6, 8-10, 24 of life for Cohort 2. Specimen for genotype testing was collected at study entry. |
| Washington D.C. |
| District of Columbia |
| 20010 |
| United States |
| Univ. of Florida Jacksonville NICHD CRS | Jacksonville | Florida | 32209 | United States |
| Rush Univ. Cook County Hosp. Chicago NICHD CRS | Chicago | Illinois | 60612 | United States |
| Lurie Children's Hospital of Chicago (LCH) CRS | Chicago | Illinois | 60614-3393 | United States |
| Boston Medical Center Ped. HIV Program NICHD CRS | Boston | Massachusetts | 02118 | United States |
| Bronx-Lebanon Hospital Center NICHD CRS | The Bronx | New York | 10457 | United States |
| St. Jude Children's Research Hospital CRS | Memphis | Tennessee | 38105-3678 | United States |
| Hospital Federal dos Servidores do Estado NICHD CRS | Rio de Janeiro | 20221-903 | Brazil |
| Hosp. Geral De Nova Igaucu Brazil NICHD CRS | Rio de Janeiro | 26030 | Brazil |
| Univ. of Sao Paulo Brazil NICHD CRS | São Paulo | 14049-900 | Brazil |
| University of Puerto Rico Pediatric HIV/AIDS Research Program CRS | San Juan | PR | 00935 | Puerto Rico |
| Umlazi CRS | Durban | KwaZulu-Natal | 4001 | South Africa |
| Fam-Cru Crs | Cape Town | 7505 | South Africa |
| Siriraj Hospital ,Mahidol University NICHD CRS | Bangkok | Bangkoknoi | 10700 | Thailand |
| FG001 | Cohort 1 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single doses of RAL: first dose (1.5 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
| FG002 | Cohort 2 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting within 48 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
| FG003 | Cohort 2 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting between 12 and 60 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
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| NOT COMPLETED |
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All enrolled infants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single doses of RAL: first dose (3 mg/kg or 2mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
| BG001 | Cohort 1 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single doses of RAL: first dose (1.5 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
| BG002 | Cohort 2 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL through 6 weeks of life starting within 48 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
| BG003 | Cohort 2 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL through 6 weeks of life starting between 12 and 60 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Customized | Gestational age at birth | Median | Full Range | weeks |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Birth weight | Median | Full Range | grams |
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| Apgar score at 1 minute | The APGAR score is an evaluation typically done at 1 minute and 5 minutes after birth to describe an infant's health. It ranges from 0 - 10, where 10 is the best possible score. Baseline table includes Apgar Score at 1 minute after birth. | Median | Full Range | Scores on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Number of Infants Who Died or Had Grade 3/4 Adverse Event Through 6 Weeks of Life | Number of infants who died or had adverse events (AEs) of Grade 3 or 4 as defined in DAIDS AE Grading Table. Events with onset dates prior to first RAL dosing and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs. | All infants who received at least one dose of RAL. Excluded one Cohort 2 RAL-naive infant who received one dose of RAL at study entry but was off study right after study entry and thus had no post entry safety data. | Posted | Count of Participants | Participants | From first dosing of RAL through 6 weeks of life |
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| Primary | AUC24 for Cohort 1 RAL Dose #1 (Within 48 Hours of Birth) | Area Under the Concentration-time Curve at 24-hour interval (AUC24) based on intensive PK sampling around Cohort 1 RAL dose #1 (within 48 hours of birth) | All Cohort 1 infants who received the first RAL dosing within 48 hours of birth and had AUC24 data for the dosing. AUC24 was missing for one Cohort 1 RAL-naive infant whose PK samples were possibly switched. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Cohort 1 RAL dose #1 (within 48 hours of birth) intensive PK sampling: within 30 min pre-dose; and 1-2, 4-8, 12 (±1), 24 (±1) hours post-dose. |
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| Primary | Cmax for Cohort 1 RAL Dose #1 (Within 48 Hours of Birth) | Maximum concentration (Cmax) for Cohort 1 dose #1 (within 48 hours of birth) | All Cohort 1 infants who received the first RAL dosing within 48 hours of birth and had Cmax data for the dosing. Cmax was missing for one Cohort 1 RAL-naive infant whose PK samples were possibly switched. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cohort 1 dose #1(within 48 hours of birth) intensive PK sampling: within 30 min pre-dose; and 1-2, 4-8, 12 (±1), 24 (±1) hours post-dose. |
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| Primary | AUC24 for Cohort 2 Initial RAL Dose (Within 48 and 12-60 Hours of Birth for RAL-naive and RAL-exposed Groups, Respectively) | Area Under the Concentration-time Curve at the 24-hour interval (AUC24) for Cohort 2 initial RAL dose (within 48 and between 12-60 hours of birth for RAL-naive and RAL-exposed, respectively). | All Cohort 2 infants who had AUC24 data for the initial RAL dosing. AUC24 were missing for 2 Cohort 2 RAL-naive infants: one was off-study right after study entry and had incomplete PK specimen collection; and one whose AUC24 could not be estimated due to possible administration of next dose before the 24 hr sample was collected. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Cohort 2 initial dose (within 48 and between 12-60 hours of birth for RAL-naive and RAL-exposed, respectively) intensive PK sampling: within 1 hour pre-dose; and 1-2, 6-10, 20-24 hours post-dose. |
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| Primary | Clast for Cohort 2 Initial RAL Dose (Within 48 and Between 12-60 Hours of Birth for RAL-naïve and RAL-exposed Groups, Respectively) | Last concentration of the drug (Clast) at 24 hour interval post dosing for the Cohort 2 initial RAL dose (within 48 and at 12-60 hours of birth for RAL-naive and RAL-exposed, respectively). This is the plasma RAL concentration from a sample collected at or close to 24 hours post dose. | All Cohort 2 infants who had Clast data for the initial RAL dosing. Clast was missing for one Cohort 2 RAL-naive infant who was off-study right after study entry and had incomplete PK specimen collection. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cohort 2 initial dose (within 48 and between 12-60 hours of birth for RAL-naive and RAL-exposed groups, respectively) intensive PK sampling: within 1 hour pre-dose; and 1-2, 6-10, 20-24 hours post-dose. |
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| Primary | RAL AUC12 for Cohort 2 at 15-18 Days of Life | Area Under the Concentration-time Curve at 12-hour interval (AUC12) of RAL for Cohort 2 at 15-18 days of life. | All infants who continued to receive RAL at or beyond Day 15-18 study visit and had AUC12 for the dosing. AUC12 were missing for 2 RAL-naive infants taken off study prior to Day 15-18 visit; 1 RAL-naive infant with delayed absorption for whom AUC12 could not be estimated; and 1 RAL-exposed infant who had incomplete PK sample collection. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Intensive PK sampling for Cohort 2 at 15-18 days of life: within 1 hour pre-dose; and 1-2, 4-6, 8-12 hours post-dose. |
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| Primary | RAL C12 for Cohort 2 at 15-18 Days of Life | RAL concentration at 12 hours (C12) for Cohort 2 at 15-18 days of life. | All infants who continued to receive RAL at or beyond Day 15-18 study visit and had C12 for the dosing. C12 were missing for 2 RAL-naive infants taken off study prior to Day 15-18 visit; 1 RAL-naive infant with delayed absorption for whom C12 could not be estimated; and 1 RAL-exposed infant who had incomplete PK sample collection. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Intensive PK sampling for Cohort 2 at 15-18 days of life: within 1 hour pre-dose; and 1-2, 4-6, 8-12 hours post-dose. |
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| Secondary | Number of Infants Who Died or Had Grade 3/4 Adverse Event Through 24 Weeks of Life | Number of infants who died or had adverse events (AEs) of Grade 3 or 4 as defined in DAIDS AE Grading Table. Events with onset dates prior to first RAL dosing and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs. | All infants who received at least one dose of RAL. Excluded was one Cohort 2 RAL-naive infant who received one dose of RAL at study entry but was off study right after study entry and thus had no post entry safety data. | Posted | Count of Participants | Participants | From first RAL dose through 24 weeks of life |
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| Secondary | Number of Infants Who Died or Had SADR of Grade 3 or 4 Through 6 Weeks of Life | Number of infants who died or had Suspected Adverse Drug Reaction (SADR) of Grade 3 or 4 as defined in DAIDS AE Grading Table. Events with onset dates prior to the first RAL dosing and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs. SADRs are AEs assessed as definitely related, probably related or possibly related to RAL. | All infants who received at least one dose of RAL. Excluded was one Cohort 2 RAL-naive infant who received one dose of RAL at study entry but was off study right after study entry and thus had no post entry safety data. | Posted | Count of Participants | Participants | From first RAL dose through 6 weeks of life |
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| Secondary | Number of Infants Who Died or Had SADR of Grade 3 or 4 Through 24 Weeks of Life | Number of infants who died or had Suspected Adverse Drug Reaction (SADR) of Grade 3 or 4 as defined in DAIDS AE Grading Table. Events with onset dates prior to the first RAL dosing and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs. SADRs are AEs assessed as definitely related, probably related or possibly related to RAL. | All infants who received at least one dose of RAL. Excluded was one Cohort 2 RAL-naive infant who received one dose of RAL at study entry but was off study right after study entry and thus had no post entry safety data. | Posted | Count of Participants | Participants | From first RAL dose through 24 weeks of life |
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| Secondary | Cohort 1 Dose #1 Neonatal RAL Elimination (CL/F) by UGT1A1 Genotype Group | Cohort 1 Dose #1 neonatal RAL elimination was represented by Clearance (CL/F), which is the volume of plasma cleared of the drug per unit time. Genotyping for polymorphisms of UGT1A1 were performed on infants who were eligible for PK sampling and were consented by their mothers/guardians (i.e. genotyping was optional) . | All Cohort 1 infants with data on CL/F (for dose #1) and UGT1A1 genotype. Excluded were: 1 Cohort 1 RAL-naive infant with missing CL/F due to possible PK specimen switch; 2 Cohort 1 RAL-naive infants with no specimen for genotype testing; 1 Cohort 1 RAL-exposed infant with CL/F and genotype data but was the only infant with (TA)5(TA)6 genotype. | Posted | Median | Inter-Quartile Range | L/hr | Cohort 1 Dose #1 Intensive PK sampling: within 30 min pre-dose; and 1-2, 4-8, 12, 24 hours post-dose. Samples for UGT1A1 genotype testing were collected at study entry. |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cohort 2 Initial Dose Neonatal RAL Elimination (CL/F) by UGT1A1 Genotype Group | Cohort 2 initial dose neonatal RAL elimination was represented by Clearance (CL/F), which is defined as the volume of plasma cleared of the drug per unit time. Genotyping for polymorphisms of UGT1A1 were performed on infants who were eligible for PK sampling and were consented by their mothers/guardians (i.e. genotyping was optional) . | All Cohort 2 infants w/ data on initial dose CL/F and UGT1A1 genotype. Exclusions: 1 RAL-naive infant who was off-study right after entry w/ incomplete PK specimens; 1 RAL-naive infant's CL/F can't be estimated due to possible administration of next dose before 24 hr sample collection; 3 RAL-naive and 4 exposed infants w/o genotype specimen. | Posted | Median | Inter-Quartile Range | L/hr | Intensive PK sampling for Cohort 2 initial dose: within 1 hour pre-dose; and 1-2, 6-10, 20-24 hours post-dose. Samples for UGT1A1 genotype testing were collected at study entry. |
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| Secondary | Cohort 2 Neonatal RAL Elimination (CL/F) at 15-18 Days of Life by UGT1A1 Genotype Group | Cohort 2 15-18 days of life dose neonatal RAL elimination was represented by Clearance (CL/F), which is defined as the volume of plasma cleared of the drug per unit time at 15-18 days of life when RAL dosing would have been 3 mg/kg twice daily. Genotyping for polymorphisms of UGT1A1 were performed on infants who were eligible for PK sampling and were consented by their mothers/guardians(i.e. genotyping was optional) . | All Cohort 2 infants with data on CL/F for Day 15-18 visit & UGT1A1 genotype. Exclusions: 1 RAL-naive infant off-study right after entry w/ incomplete PK specimens; 1 RAL-naive infant withdrew consent; 1 RAL-naive infant stopped RAL after wk 4; 1 RAL-exposed infant w/ incomplete PK specimens; 3 RAL-naive and 4 exposed infants w/o genotype specimen. | Posted | Median | Inter-Quartile Range | L/hr | Intensive PK sampling for Cohort 2 at 15-18 days of life: within 1 hour pre-dose; and 1-2 hours post-dose, 4-6, 8-12 hours post-dose. Samples for UGT1A1 genotype testing were collected at study entry. |
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| Secondary | Number of Cohort 1 Infants With Hyperbilirubinemia by UGT1A1 Genotype | Hyperbilirubinemia was defined as total bilirubin exceeding 16.0 mg/dL or receipt of phototherapy, or transfusion therapy, or other therapies for hyperbilirubinemia or elevated bilirubin. | The intent of this Outcome Measure was to investigate the association between UGT1A1 genotypes with hyperbilirubinemia, however no infants had hyperbilirubinemia. | Posted | Specimens for bilirubin testing were collected at study entry; Days 3-4, 7-10 of life; and Weeks 2, 6, 24 of life for Cohort 1. Specimen for genotype testing was collected at entry. |
|
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| Secondary | Number of Cohort 2 Infants With Hyperbilirubinemia by UGT1A1 Genotype | Hyperbilirubinemia was defined as total bilirubin exceeding 16.0 mg/dL or receipt of phototherapy, or transfusion therapy, or other therapies for hyperbilirubinemia or elevated bilirubin. | The intent of this Outcome Measure was to investigate the association between UGT1A1 genotypes with hyperbilirubinemia, however no infants had hyperbilirubinemia. | Posted | Specimens for bilirubin testing were collected at study entry; after 2nd dose; Days 6-9, 15-18, 28-32 of life; and Weeks 5-6, 8-10, 24 of life for Cohort 2. Specimen for genotype testing was collected at study entry. |
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| Secondary | Number of Cohort 1 Infants With Hyperbilirubinemia by SLCO1B3 Genotype | Hyperbilirubinemia was defined as total bilirubin exceeding 16.0 mg/dL or receipt of phototherapy, or transfusion therapy, or other therapies for hyperbilirubinemia or elevated bilirubin. | The intent of this Outcome Measure was to investigate the association between SLCO1B3 genotypes with hyperbilirubinemia, however no infants had hyperbilirubinemia. | Posted | Specimens for bilirubin test were collected at study entry; Days 3-4, 7-10 of life; and Weeks 2, 6, 24 of life for Cohort 1. Specimen for genotype testing was collected at study entry. |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Cohort 2 Infants With Hyperbilirubinemia by SLCO1B3 Genotype | Hyperbilirubinemia was defined as total bilirubin exceeding 16.0 mg/dL or receipt of phototherapy, or transfusion therapy, or other therapies for hyperbilirubinemia or elevated bilirubin. | The intent of this Outcome Measure was to investigate the association between SLCO1B3 genotypes with hyperbilirubinemia, however no infants had hyperbilirubinemia. | Posted | Specimens for bilirubin testing were collected at study entry; after 2nd dose; Days 6-9, 15-18, 28-32 of life; and Weeks 5-6, 8-10, 24 of life for Cohort 2. Specimen for genotype testing was collected at study entry. |
|
|
From first RAL dose through 24 weeks of life
All Adverse Events (AEs) including diagnoses, signs/symptoms and abnormal laboratory test results mentioned in the "Study Description" section. Events with onset dates prior to first RAL dose and congenital anomalies assessed as baseline by the study team were considered baseline events and not AEs.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort1 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single RAL doses: first dose (3 mg/kg or 2 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. | 0 | 10 | 3 | 10 | 10 | 10 |
| EG001 | Cohort1 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single RAL doses: first dose (1.5 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG002 | Cohort2 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting within 48 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. | 0 | 25 | 7 | 25 | 24 | 25 |
| EG003 | Cohort2 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting between 12 to 60 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. | 0 | 10 | 2 | 10 | 9 | 10 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia neonatal | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Congenital syphilis | Congenital, familial and genetic disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Bronchiolitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Respiratory syncytial virus bronchiolitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood glucose decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Haematocrit decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Hypertension neonatal | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial septal defect | Congenital, familial and genetic disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Congenital umbilical hernia | Congenital, familial and genetic disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Craniosynostosis | Congenital, familial and genetic disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Laryngomalacia | Congenital, familial and genetic disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pulmonary artery stenosis congenital | Congenital, familial and genetic disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Eye discharge | Eye disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Infantile spitting up | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Infantile vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Oral mucosal discolouration | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Umbilical hernia | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vessel puncture site bruise | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia neonatal | Hepatobiliary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Genital candidiasis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Otitis media acute | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Skin candida | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Tinea versicolour | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood glucose decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood potassium increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Cardiac murmur | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Fontanelle bulging | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypertonia | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Jaundice neonatal | Pregnancy, puerperium and perinatal conditions | MedDRA 21.0 | Systematic Assessment |
| |
| Acquired hydrocele | Reproductive system and breast disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Breast induration | Reproductive system and breast disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Penile erythema | Reproductive system and breast disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Cyanosis neonatal | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Oropharyngeal plaque | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Papule | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Seborrhoea | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pallor | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
|
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Melissa Allen, Director, IMPAACT Operations Center | Family Health International (FHI 360) | (919) 405-1429 | mallen@fhi360.org |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 3, 2017 | Apr 23, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068898 | Raltegravir Potassium |
| ID | Term |
|---|---|
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Clopper-Pearson Confidence Interval (CI) |
| 31 |
| 2-Sided |
| 90 |
| 18.7 |
| 46.6 |
| Other |
Point and 90% CI estimates of percentage Cohort 2 infants who died or had grade 3/4 AE through 6 weeks of life. |
| OG002 | Cohort 1 RAL-exposed 1.5 mg/kg | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single RAL doses: first dose (1.5 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
|
|
| OG002 | Cohort 1 RAL-exposed: 1.5 mg/kg for First Dose | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single doses: first dose (1.5 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
|
|
Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection.
Raltegravir: Daily RAL dosing through 6 weeks of life starting between 12 and 60 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life
|
|
Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection.
Raltegravir: Daily RAL dosing through 6 weeks of life starting between 12 and 60 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life.
|
|
|
|
|
|
| OG002 | Cohort 1 Total | Full term Infants, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single doses: first dose (3 mg/kg, 2 mg/kg or 1.5 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
| OG003 | Cohort 2 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting within 48 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
| OG004 | Cohort 2 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting between 12 to 60 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life |
| OG005 | Cohort 2 Total | Full term Infants, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting within 48 hours of birth and between 12 to 60 hours of birth for in utero RAL-naive and RAL-exposed infants, respectively: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
|
|
|
| OG002 | Cohort 1 Total | Full term Infants, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single RAL doses: first dose (3 mg/kg, 2 mg/kg or 1.5 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
| OG003 | Cohort 2 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting within 48 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
| OG004 | Cohort 2 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting between 12 to 60 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life |
| OG005 | Cohort 2 Total | Full term Infants, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting within 48 hours of birth and between 12 to 60 hours of birth for RAL-naive and RAL-exposed infants, respectively: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
|
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| OG002 | Cohort 1 Total | Full term Infants, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: RAL was given as oral granules for suspension. Two single RAL doses: first dose (3 mg/kg, 2 mg/kg or 1.5 mg/kg) within 48 hours of birth and second dose (3 mg/kg) at 7-10 days of life. |
| OG003 | Cohort 2 RAL-naive | Full term Infants not exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting within 48 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
| OG004 | Cohort 2 RAL-exposed | Full term Infants exposed in utero to maternal RAL, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting between 12 to 60 hours of birth: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
| OG005 | Cohort 2 Total | Full term Infants, ≥2000 grams and ≥37 weeks gestational age at birth, born to women living with HIV-1 infection and at risk of acquiring HIV-1 infection. Raltegravir: Daily RAL dosing through 6 weeks of life starting within 48 hours of birth and between 12 to 60 hours of birth for RAL-naive and RAL-exposed infants, respectively: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life. |
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| OG004 | (TA)6(TA)7 | Cohort 2 infants whose UGT1A1 genotype were (TA)6(TA)7. |
| OG005 | (TA)7(TA)7 | Cohort 2 infants whose UGT1A1 genotype were (TA)7(TA)7. |
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