Abstract
Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)-infected youth.Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥1 log10 reduction between baseline and week 24.Results. The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/μL (4.6%).Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 413-422 |
| Number of pages | 10 |
| Journal | Clinical Infectious Diseases |
| Volume | 58 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 2014 |
Keywords
- adverse event
- pediatric HIV
- pharmacokinetics
- raltegravir
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
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In: Clinical Infectious Diseases, Vol. 58, No. 3, 02.2014, p. 413-422.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years
AU - Nachman, Sharon
AU - Zheng, Nan
AU - Acosta, Edward P.
AU - Teppler, Hedy
AU - Homony, Brenda
AU - Graham, Bobbie
AU - Fenton, Terence
AU - Xu, Xia
AU - Wenning, Larissa
AU - Spector, Stephen A.
AU - Frenkel, Lisa M.
AU - Alvero, Carmelita
AU - Worrell, Carol
AU - Handelsman, Edward
AU - Wiznia, Andrew
AU - Moultrie, Harry
AU - Kindra, Gurpreet
AU - Sanders, Margaret Ann
AU - Williams, Ruth
AU - Jensen, Jennifer
AU - Acevedo, Midnela
AU - Fabregas, Lizbeth
AU - Jurgrau, Andrea
AU - Foca, Marc
AU - Higgins, Alice
AU - Deville, Jaime G.
AU - Nielsen-Saines, Karin
AU - Carter, Michele F.
AU - Swetnam, John
AU - Wilson, Joan
AU - Donnelly, Margaret
AU - Akleh, Siham
AU - Rigaud, Mona
AU - Kaul, Aditya
AU - Patel, Nehali
AU - Gaur, Aditya
AU - Utech, L. Jill
AU - Cardoso, Edmundo
AU - Moreira, Ana Maria
AU - Santos, Breno
AU - Bobat, Raziya
AU - Mngqibisa, Rosie
AU - Burey, Marlene
AU - Abadi, Jacob
AU - Rosenberg, Michael
AU - Luzuriaga, Katherine
AU - Picard, Donna
AU - Pagano-Therrien, Jessica
AU - Dittmer, Sylvia
AU - Ndiweni, Hilda Ntatule
AU - Patel, Amisha
AU - Delrey, Michelle
AU - McMullen-Jackson, Chivon
AU - Paul, Mary E.
AU - Melvin, Ann
AU - Venema-Weiss, Corry
AU - Lane, Jenna
AU - Beneri, Christy
AU - Ferraro, Denise
AU - Infanzon, Erin
AU - McAuley, James B.
AU - Aziz, Mariam
AU - McNichols, Maureen
AU - Pelton, Stephen
AU - McLaud, Deb
AU - Clarke, Diana
AU - Zeichner, Steven
AU - Akar, Arezou
AU - Thompson, Deidre
AU - Douglas, Steven D.
AU - Rutstein, Richard M.
AU - Vincent, Carol A.
AU - Vachon, Mary Elizabeth
AU - Cavallo, Martha
AU - Purswani, Murli Udharam
AU - Masheto, Gaerolwe
AU - Ogwu, Anthony
AU - Kakhu, Tebogo
AU - Viani, Rolando M.
AU - Darcey, Anita
AU - Norris, Kimberly
AU - Burchett, Sandra K.
AU - Kneut, Catherine
AU - Karthas, Nancy
AU - Casey, Denise
AU - Emmanuel, Patricia
AU - Lujan-Zilbermann, Jorge
AU - Rana, Sohail
AU - Houston, Patricia
AU - Mengistab, Mulu
AU - Rathore, Mobeen
AU - Mirza, Ayesha
AU - Gayton, Tabetha
AU - Barr, Emily
AU - Dunn, Jennifer
AU - Hahn, Kerry
AU - Eysallenne, Zulma
AU - Howard, F. Sholar
AU - Graham, Kathleen
AU - Negra, Marinella Della
AU - Queiroz, Wladimir
AU - Lian, Yu Ching
AU - Wara, Diane
AU - Ruel, Ted
AU - Vandyke, Russell
AU - Reilly, Patricia
AU - Bradford, Sheila
AU - Van Rensburg, Anita Janse
AU - Dobbels, Els
AU - Bester, Marietjie
AU - Bamji, Mahrukh
AU - Paul, Santa
AU - Sarza, Mirala
AU - Kovacs, Andrea
AU - Homans, James
AU - Spencer, Lashonda
AU - Hofer, Cristna
AU - Abreu, Thalita
AU - Oliveira, Ricardo
AU - Joao, Esau C.
AU - Pinto, Jorge
AU - Ferreira, Flavia
AU - Kakehasi, Fabiana
AU - Cervi, Maria Celia
AU - Isaac, Marcia De Lima
AU - Losso, Marcelo H.
AU - Stankievich, Erica
AU - Foradori, Irene
AU - Tucker, Diane
AU - Church, Joseph
AU - Belzer, Marvin
AU - Hopkins, Johns
AU - Ellen, Jonathan
AU - Agwu, Allison
AU - Laurel, Borkovic
N1 - Funding Information: Participating sites and site personnel include: Shandukani Research (Harry Moultrie, MD MSc; Angela Oosthuizen, BPharm; Gurpreet Kindra, MD PhD); Chicago Children’s (Margaret Ann Sanders, MPH; Ruth Williams, RN; Jennifer Jensen, PNP); San Juan City Hospital PR NICHD (Midnela Acevedo, MD; Lizbeth Fabregas, MS); Columbia IMPAACT (Andrea Jurgrau, PNP; Marc Foca, MD; Alice Higgins, RN); UCLA–Los Angeles/Brazil AIDS Consortium (Jaime G. Deville, MD; Karin Nielsen-Saines, MD; Michele F. Carter, RN); DUMC Pediatric (John Swetnam, MD; Joan Wilson, RN, BSN; Margaret Donnelly, PA-C); NYU NY NICHD, supported in part by grant UL1 TR000038 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) (Siham Akleh, RN; Mona Rigaud, MD; Aditya Kaul, MD); St Jude/UTHSC (Nehali Patel, MD; Aditya Gaur, MD; L. Jill Utech, RN, MSN); Hospital Nossa Senhora da Con-ceicao (Edmundo Cardoso, MD; Ana Maria Moreira, MD; Breno Santos, MD); Durban Pediatric HIV (Raziya Bobat, MD; Rosie Mngqibisa, MS); Jacobi Medical Center Bronx NICHD (Marlene Burey, PNP; Jacob Abadi, MD; Michael Rosenberg, MD); WNE Maternal Pediatric Adolescent AIDS (Katherine Luzuriaga, MD; Donna Picard, RN; Jessica Pagano-Therrien, RN, PNP; CTSI: UL1TR000161); Soweto IMPAACT (Sylvia Dittmer, MBBCH, DCH; Hilda Ntatule Ndiweni, BC, Ed ET Admin; Amisha Patel, BPharm); Texas Children’s Hospital (Michelle DelRey, RN; Chivon McMullen-Jackson, RN, BSN, CCRP; Mary E. Paul, MD); Seattle Children’s Hospital (Ann Melvin, MD, MPH; Corry Venema-Weiss, ARNP; Jenna Lane, ARNP). This publication was supported by the NCATS of the NIH under Award Number UL1TR000423); SUNY Stony Brook NICHD (Christy Beneri, DO; Denise Ferraro, FNP; Erin Infanzon); Rush University Cook County Hospital Chicago NICHD (James B McAuley, MD, MPH; Mariam Aziz, MD; Maureen McNichols, RN, MSN, CCRC); Boston Medical Center Pediatric HIV Program NICHD (Stephen Pelton, MD; Deb McLaud, RN; Diana Clarke, PharmD); Children’s National Medical Center Washington DC NICHD (Steven Zeichner, MD, PhD; Arezou Akar, MPH; Deidre Thompson, RN); The Children’s Hospital of Philadelphia IMPAACT (Steven D. Douglas, MD, Richard M. Rutstein, MD, Carol A. Vincent, PhD, CRNP); Bronx-Lebanon Hospital IMPAACT (Mary Elizabeth Vachon, MPH; Martha Cavallo, NP; Murli Udharam Purswani, MD); Gaborone Prevention/Treatment Trials (Gaerolwe Masheto, MD; Anthony Ogwu, MD, MPH; Tebogo Kakhu, BS, RN); University of California San Diego Maternal, Child, and Adolescent HIV (Rolando M. Viani, MD, MTP; Anita, Darcey, RN; Kimberly Norris, RN, BSN); Children’s Hospital of Boston NICHD (Sandra K. Burchett, MD, MS; Catherine Kneut, RN, MS, CPNP; Nancy Karthas, RN, MS, CPNP); University of South Florida–Tampa NICHD (Denise Casey, RN; Patricia Emmanuel, MD; Jorge Lujan-Zilbermann, MD); Howard University, Washington DC, NICHD (Sohail Rana, MD; Patricia Houston, MS; Mulu Mengistab, Pharm D); University of Florida College of Medicine, Jacksonville NICHD (Mobeen Rathore, MD; Ayesha Mirza, MD; Tabetha Gayton, MS, RN, FNP; The UF CTSI is supported in part by the NIH/National Center for Research Resources (NCRR) Clinical and Translational Science Award UL1 RR029890); University of Colorado Denver NICHD (Emily Barr, CPNP, CNM, MSN; Jennifer Dunn, FNP-C; Kerry Hahn, BS, CCRP); South Florida CDC Fort Lauderdale NICHD (Zulma Eysallenne, RN; F. Sholar Howard, ARNP; Kathleen Graham, Pharm D); Instituto de Infectologia Emílio Ribas Sao Paulo Brazil NICHD (Marinella Della Negra, MD, PhD; Wladimir Queiroz, MD, MSc; Yu Ching Lian, MD, MSc); University of California, San Francisco NICHD (Diane Wara, MD; Ted Ruel, MD; This publication was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131); Tulane University New Orleans NICHD (Russell VanDyke, MD; Patricia Reilly, RN; Sheila Bradford, RN); Stellenbosch University (Anita Janse van Rensburg, RN; Els Dobbels, MD; Marietjie Bester, RN); Metropolitan Hospital NICHD (Mahrukh Bamji, MD; Santa Paul, MD; Mirala Sarza, MS); USC LA NICHD (Andrea Kovacs, MD; James Homans, MD; LaShonda Spencer, MD); Inst of Pediatrics Fed Univ Rio de Janeiro NICHD (Cristna Hofer, MD, PhD; Thalita Abreu, MD; Ricardo Oliveira, MD); Hospital Federal dos Servi-dores do Estado Rio de Janeiro NICHD (Esau C. Joao, MD, PhD); SOM Federal University Minas Gerais Brazil NICHD (Jorge Pinto, MD; Flavia Fer-reira, MD; Fabiana Kakehasi, MD); University of Sao Paulo Brazil NICHD (Maria Celia Cervi; Marcia De Lima Isaac); Hospital General de Agudos Buenos Aires Argentina NICHD (Marcelo H. Losso, MD; Erica Stankievich, MD; Irene Foradori, MD); Children’s Hospital of Los Angeles NICHD (Diane Tucker, MSN; Joseph Church, MD; Marvin Belzer, MD, FACP, FSAM); and Johns Hopkins University Baltimore NICHD (Jonathan Ellen MD; Allison Agwu MD; Laurel Borkovic MS ED). Funding Information: Financial support. Overall support for the IMPAACT Group was provided by the NIAID (grant number U01 AI068632), the NICHD, and the National Institute of Mental Health (grant number AI068632). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the NIAID cooperative agreement 5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group and 1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C), and by Merck & Co Inc.
PY - 2014/2
Y1 - 2014/2
N2 - Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)-infected youth.Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥1 log10 reduction between baseline and week 24.Results. The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/μL (4.6%).Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses.
AB - Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)-infected youth.Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥1 log10 reduction between baseline and week 24.Results. The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/μL (4.6%).Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses.
KW - adverse event
KW - pediatric HIV
KW - pharmacokinetics
KW - raltegravir
UR - http://www.scopus.com/inward/record.url?scp=84892742221&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892742221&partnerID=8YFLogxK
U2 - 10.1093/cid/cit696
DO - 10.1093/cid/cit696
M3 - Article
C2 - 24145879
AN - SCOPUS:84892742221
SN - 1058-4838
VL - 58
SP - 413
EP - 422
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 3
ER -