Evaluating the Safety and Pharmacokinetics of Raltegravir in Infants

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01828073
First received: April 5, 2013
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

This study will evaluate the safety and pharmacokinetics (PKs) of exposure (in utero or intrapartum) to raltegravir (RAL) in infants born to HIV-infected pregnant women who received RAL during pregnancy. (Pharmacokinetics are the various interactions between a drug and the body.) This study will also seek to develop an infant RAL dosing regimen to be evaluated in a follow-up study.


Condition Intervention
HIV Infections
Drug: Raltegravir

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Raltegravir Pharmacokinetics and Safety in Neonates

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Neonatal RAL elimination (t 1/2) [ Time Frame: Measured during PK sampling at birth/delivery visit ] [ Designated as safety issue: No ]
    Timing of birth/delivery visit is not predetermined and will vary for each mother/infant pair

  • RAL maternal cord blood ratio (Cohort 1 only) [ Time Frame: Measured at birth/delivery visit ] [ Designated as safety issue: No ]
    Timing of birth/delivery visit is not predetermined and will vary for each mother/infant pair

  • Infant adverse events of Grade 3 or 4 [ Time Frame: Measured through Week 20 (Cohort 1); Measured through Week 6 (Cohort 2) ] [ Designated as safety issue: Yes ]
  • Adverse birth outcome: stillbirth (Cohort 1 only) [ Time Frame: Measured at birth/delivery visit ] [ Designated as safety issue: Yes ]
    Timing of birth/delivery visit is not predetermined and will vary for each mother/infant pair

  • Adverse birth outcome: low birth weight (Cohort 1 only) [ Time Frame: Measured at birth/delivery visit ] [ Designated as safety issue: Yes ]
    Timing of birth/delivery visit is not predetermined and will vary for each mother/infant pair

  • Total bilirubin (in infant) [ Time Frame: Measured at birth/delivery visit and at Week 1-2 visit ] [ Designated as safety issue: Yes ]
    Timing of birth/delivery visit is not predetermined and will vary for each mother/infant pair

  • Direct bilirubin (in infant) [ Time Frame: Measured at birth/delivery visit and at Week 1-2 visit ] [ Designated as safety issue: Yes ]
    Timing of birth/delivery visit is not predetermined and will vary for each mother/infant pair

  • Infant death [ Time Frame: Measured through Week 20 (Cohort 1); Measured through Week 6 (Cohort 2) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Optional genotyping for polymorphism of UGT1A1 from infants who are eligible for PK sampling as described in the protocol [ Time Frame: Measured during PK sampling at birth/delivery visit ] [ Designated as safety issue: No ]
    Timing of birth/delivery visit is not predetermined and will vary for each mother/infant pair


Estimated Enrollment: 45
Study Start Date: April 2011
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Cohort 1: HIV-infected women & their full-term infants
The group will consist of HIV-infected pregnant women receiving 400 mg raltegravir (RAL) twice daily for at least 2 weeks prior to delivery and continuing to receive ARVs during labor. The group will also include the infants born to these women.
Drug: Raltegravir
No study-specific drugs will be given to women or infants during this study. Women will be receiving RAL for clinical indications outside of the study.
Other Name: RAL
Cohort 2: HIV-infected women & their low birth weight infants
The group will consist of HIV-infected pregnant women receiving at least one dose of 400 mg RAL within 2 to 24 hours prior to delivery. The group will also include the women's infants who weigh less than or equal to 2,500 grams at birth.
Drug: Raltegravir
No study-specific drugs will be given to women or infants during this study. Women will be receiving RAL for clinical indications outside of the study.
Other Name: RAL

Detailed Description:

This study will enroll participants in two cohorts. Cohort 1 is now closed to enrollment. Researchers are enrolling participants in Cohort 2.

Cohort 1 will include mother-infant pairs in which the HIV-infected pregnant mother will have received RAL 400 mg twice daily for at least 2 weeks prior to delivery and will continue antiretroviral (ARV) drugs during labor. Mother/infant pairs will be enrolled prior to delivery, and women will be followed until discharge from the labor/delivery unit. At delivery, cord blood will be drawn and a single blood sample will be collected from the woman.

All infants will undergo a medical history, physical examination, and blood draw at the Week 1-2 visit and Week 20 visit. Infants who meet certain criteria defined in the protocol will be eligible for PK sampling at the birth visit. These infants will have one blood sample collected at 1 to 5, 8 to 14, 18 to 24, and 30 to 36 hours after birth. Infants not eligible for PK sampling will undergo a blood draw at 8 to 14 hours and 30 to 36 hours after birth.

Optional genotyping for UGT1A1 polymorphisms will be done using dried blood spot on filter paper. (UGT1A1 is the enzyme primarily responsible for RAL metabolism.) Only infants who have PK sampling will have genotyping done.

No study-specific drugs will be given to women or infants during this study. Women will be receiving RAL for clinical indications outside of the study. Infants will receive standard of care ARV therapy for prevention of mother-to-child transmission (PMTCT) as prescribed by their primary care physicians. Infants will be followed for 20 weeks after birth.

Cohort 2 will enroll mother-infant pairs in which the HIV-infected pregnant woman will have received at least one dose of 400 mg of RAL within 2 to 24 hours prior to delivery, and their infants will weigh less than or equal to 2,500 grams at birth. Participants will take part in most of the same study procedures as participants in Cohort 1, except infants will only be followed for 6 weeks after birth.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

This study will enroll two cohorts: Cohort 1 will enroll HIV-infected pregnant women and their full-term infants, and Cohort 2 will enroll HIV-infected pregnant women and their low birth weight infants.

Criteria

Enrollment into Cohort 1 is now closed.

Cohort 1: Maternal Inclusion Criteria

  • Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. The same method may be used at both time points. All samples tested must be whole blood, serum, or plasma. More information on this criterion can be found in the protocol.
  • 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.

Cohort 1: Maternal Exclusion Criteria

  • Receipt of disallowed medications within 4 weeks prior to enrollment

Cohort 1: Infant Inclusion Criteria

Infants are enrolled prior to delivery so there are no infant inclusion criteria. Only infants who meet the following criteria will be eligible for PK blood sampling:

  • 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 described in protocol. If these medications are required for the infant's care, the infant will be ineligible for further PK sampling. Data will be obtained up to the time of the introduction of the disallowed medication, but such infant will not be considered one of the evaluable 15 infants.

Cohort 1: Infant 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 will allow enrollment of mother-infant (M-I) pairs at two time points: prior to and within 48 hours after delivery.

  • For enrollment prior to delivery, the mother must meet all the eligibility criteria (i.e., there are no infant eligibility criteria for prenatal enrollment). However, only infants who meet all the eligibility criteria will have PK blood sampling performed. Infants must be PK eligible and then meet the definition of evaluable to contribute to the sample size of 15 evaluable infants. PK ineligible infants will remain in the study and will be followed for safety.
  • For enrollment within 48 hours after delivery, both mother and infant(s) must meet all the eligibility criteria. For multiple births, only infants who meet all the eligibility criteria will be enrolled.

Cohort 2: Maternal Inclusion Criteria: M-I pairs enrolled prior to delivery

  • Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. All samples tested must be whole blood, serum, or plasma. More information on this criterion can be found in the protocol.
  • 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 definied by the country in which she resides. If not, informed consent must be signed by a legal guardian.

Cohort 2: Maternal Exclusion Criteria: M-I pairs enrolled prior to delivery

  • Receipt of disallowed medications within 4 weeks prior to enrollment or intent to be on any of the disallowed medications prior to delivery. Note: Infant(s) of a woman who received any of the disallowed medications will be ineligible for PK sampling.

Cohort 2: Infant PK Blood Sampling Eligibility Criteria: M-I pairs enrolled prior to delivery

Infants are enrolled prior to delivery so there are no infant inclusion criteria. Only infants who meet the following criteria will be 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 as described in the protocol. If these medications are required for the infant's care, the infant will be ineligible for further PK sampling. Data will be obtained up to the time of the introduction of the disallowed medication, but such infant will not be considered one of the evaluable 15 infants if fewer than 3 PK samples from the first 5 time points are collected.
  • 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

Cohort 2: Maternal Inclusion Criteria: M-I pairs enrolled after delivery

  • Documentation of HIV-1 infection as described in the protocol. Enrollment is allowed if an initial HIV test is positive and a confirmatory test has been drawn and is pending.
  • 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.

Cohort 2: Maternal Exclusion Criteria: M-I pairs enrolled after delivery

  • Receipt of disallowed medications within 4 weeks prior to delivery

Cohort 2: Infant Inclusion Criteria: M-I pairs enrolled after delivery

  • Infant birth weight less than or equal to 2,500 grams
  • Infant less than or equal to 48 hours of age

Cohort 2: Infant Exclusion Criteria: M-I pairs enrolled after delivery

  • Received disallowed medications as described in the protocol
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01828073

Locations
United States, California
Usc La Nichd Crs Recruiting
Alhambra, California, United States, 91803
Contact: Eva A. Operskalski, Ph.D.    626-457-5820    eva@usc.edu   
University of California, UC San Diego CRS Recruiting
La Jolla, California, United States, 92093-0672
Contact: Kimberly Norris, B.S.N., R.N.    858-534-9204    kanorris@ucsd.edu   
Miller Children's Hosp. Long Beach CA NICHD CRS Recruiting
Long Beach, California, United States, 90806
Contact: Janielle Jackson-Alvarez    562-933-8666    jjackson-alvarez@memorialcare.org   
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS Withdrawn
Los Angeles, California, United States, 90095-1752
David Geffen School of Medicine at UCLA NICHD CRS Recruiting
Los Angeles, California, United States, 90095-1752
Contact: Michele F. Carter, B.S., R.N.    310-206-6369    mfcarter@mednet.ucla.edu   
Univ. of California San Francisco NICHD CRS Completed
San Francisco, California, United States, 94143
United States, Colorado
Univ. of Colorado Denver NICHD CRS Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Emily Barr, C.P.N.P.    720-777-6752    emily.barr@childrenscolorado.org   
United States, Florida
Pediatric Perinatal HIV Clinical Trials Unit CRS Not yet recruiting
Miami, Florida, United States, 33136
Contact: Patricia Bryan, R.N.    305-243-2700    pbryan@med.miami.edu   
United States, Illinois
Rush Univ. Cook County Hosp. Chicago NICHD CRS Withdrawn
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins Univ. Baltimore NICHD CRS Recruiting
Baltimore, Maryland, United States, 21287
Contact: Thuy Anderson, R.N., B.S.N.    443-287-8942    tander34@jhmi.edu   
United States, Massachusetts
Boston Medical Center Ped. HIV Program NICHD CRS Recruiting
Boston, Massachusetts, United States, 02118
Contact: Debra McLaud, R.N.    617-414-5813    demclaud@bmc.org   
WNE Maternal Pediatric Adolescent AIDS CRS Withdrawn
Worcester, Massachusetts, United States, 01605
United States, New Jersey
Rutgers - New Jersey Medical School CRS Withdrawn
Newark, New Jersey, United States, 07103
United States, New York
Jacobi Med. Ctr. Bronx NICHD CRS Recruiting
Bronx, New York, United States, 10461
Contact: Marlene Burey    718-918-4783    marlene.burey@nbhn.net   
Bronx-Lebanon CRS Not yet recruiting
Bronx, New York, United States, 10457
Contact: Mary-Elizabeth Vachon, M.P.H.    718-960-1016    mvachon@bronxleb.org   
Bronx-Lebanon Hospital Center NICHD CRS Recruiting
Bronx, New York, United States, 10457
Contact: Martha Cavallo, A.N.P., C.R.N.P.    718-960-1010    mcavallo@bronxleb.org   
Metropolitan Hosp. NICHD CRS Withdrawn
New York, New York, United States, 10029
Nyu Ny Nichd Crs Withdrawn
New York, New York, United States, 10016
United States, North Carolina
DUMC Ped. CRS Withdrawn
Durham, North Carolina, United States, 27710
United States, Tennessee
St. Jude Children's Research Hospital CRS Recruiting
Memphis, Tennessee, United States, 38105-3678
Contact: Laura J. Utech, R.N., M.S.N., C.C.R.C.    901-595-3490    jill.utech@stjude.org   
Regional Med. Ctr. at Memphis Withdrawn
Memphis, Tennessee, United States, 38103
United States, Washington
Seattle Children's Research Institute CRS Recruiting
Seattle, Washington, United States, 98101
Contact: Amanda Robson, B.S.    206-884-1535    amanda.robson@seattlechildrens.org   
Univ. of Washington NICHD CRS Not yet recruiting
Seattle, Washington, United States, 98195
Contact: Amanda Robson Nuss, B.S.    206-884-1535    amanda.robson@seattlechildrens.org   
UW Medicine - Harborview Med. Ctr., Northwest Family Ctr. Not yet recruiting
Seattle, Washington, United States, 98104-2499
Contact: Corry Venema-Weiss, A.R.N.P.    206-884-7869    corry.venemaweiss@seattlechildrens.org   
Puerto Rico
San Juan City Hosp. PR NICHD CRS Not yet recruiting
San Juan, Puerto Rico, 00936
Contact: Lizbeth Fabregas-Troche, B.S., M.S.    787-764-3083    lfabregas@sanjuanciudadpatria.com   
Sponsors and Collaborators
Investigators
Study Chair: Diana F. Clarke, PharmD Boston Medical Center
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01828073     History of Changes
Other Study ID Numbers: P1097, 11790, IMPAACT P1097
Study First Received: April 5, 2013
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014