A PK and Salvage Study for Children With HIV-infection

Tracking Information
First Submitted Date ICMJE	May 20, 2007
First Posted Date ICMJE	May 22, 2007
Last Update Posted Date	March 27, 2015
Study Start Date ICMJE	October 2003
Actual Primary Completion Date	November 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 21, 2007)	Intensive 0-12h PK sampling for plasma levels of LPV and SQV, and blood sampling. CD4 viral load safety lab every 3 months. [ Time Frame: 96 week ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00476359 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A PK and Salvage Study for Children With HIV-infection
Official Title ICMJE	Lopinavir/r Plus Saquinavir Salvage Therapy in HIV-infected Children With NRTI and/or NNRTI Failure: PK and Two-year Treatment Follow up
Brief Summary	To evaluate the pharmacokinetics (PK) of LPV/r with saquinavir in HIV-1 infected children. To evaluate treatment response (clinical, immunological and virological) to LPV/r, SQV in Thai children.
Detailed Description	The PK and 24 week data has been published in Pediatric Infectious Diseases Journal. It showed that plasma drug concentrations of saquinavir, lopinavir and ritonavir were at the higher limits of expected ranges for adult treatment at approved dosages (1000/100 mg BID for saquinavir, 400/100 mg BID for lopinavir/r). The regimen was well tolerated and showed significant CD4 rise and VL decline at 48 weeks.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	HIV Infections
Intervention ICMJE	Drug: Lopinavir/r plus saquinavir; lopinavir/ritonavir 230/57.5 mg/m2 orally twice daily and saquinavir 50 mg/kg orally twice daily
Study Arms	double-boosted PI; double-boosted protease inhibitor combination; Intervention: Drug: Lopinavir/r plus saquinavir
Publications *	Ananworanich J, Kosalaraksa P, Hill A, Siangphoe U, Bergshoeff A, Pancharoen C, Engchanil C, Ruxrungtham K, Burger D; HIV-NAT 017 Study Team. Pharmacokinetics and 24-week efficacy/safety of dual boosted saquinavir/lopinavir/ritonavir in nucleoside-pretreated children. Pediatr Infect Dis J. 2005 Oct;24(10):874-9.; Kosalaraksa P, Engchanil C, Bunupuradah T, Luesomboon W, Sunthornkachit R, Bunruen S, Intasan J, Jupimai T, Hirunwadee N, Lumbiganon P, Ruxrungtham K on behalf of the PREDICT study team. Prevalence of anemia and impact of iron status in Thai and Cambodian HIV infected children with moderate immunosuppression (PREDICT study), poster No. TUPEB 137. Poster presented at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, Australia, July 22-25, 2007; Jasper van der Lugt, Torsak Bunupuradah, Pope Kosalaraksa, Thanyawee Puthanakit, Chulapan Engchanil, Waraporn Sakornjun, Meena Gorowara, ROCHE, Kiat Ruxrungtham, David Burger, Jintanat Ananworanich: Therapeutic Drug Monitoring of lopinavir and saquinavir in Thai HIV infected Children. Poster will be presented at the 15th Conference on Retroviruses and Opportunistic Infections, Boston, USA, February 3-7, 2008.; Torsak Bunupuradah, Pope Kosalaraksa, Chulapan Engchanil, Pitch Boonrak, Tawan Hirunyanulux, Sasiwimol Ubolyam, Pagakrong Lumbiganon, Kiat Ruxrungtham, Emily Labriola-Tompkins, Jintanat Ananworanich, and HIV-NAT 017 Study Team: Efficacy and safety of double boosted SQV/LPV/r combination at 96 weeks in Thai children who have failed NRTI/NNRTI-.based regimens. Abstract # R-143. Abstract will be presented at the 15th Conference on Retroviruses and Opportunistic Infections, Boston, USA, February 3-7, 2008.; Bunupuradah T, van der Lugt J, Kosalaraksa P, Engchanil C, Boonrak P, Puthanakit T, Mengthaisong T, Mahanontharit A, Lumbiganon P, Tompkins E, Burger D, Ruxrungtham K, Ananworanich J; HIV-NAT 017 Study Team. Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks. Antivir Ther. 2009;14(2):241-8.; Kosalaraksa P, Bunupuradah T, Engchanil C, Boonrak P, Intasan J, Lumbiganon P, Burger D, Ruxrungtham K, Schutz M, Ananworanich J; HIV-NAT 017 Study Team. Double boosted protease inhibitors, saquinavir, and lopinavir/ritonavir, in nucleoside pretreated children at 48 weeks. Pediatr Infect Dis J. 2008 Jul;27(7):623-8. doi: 10.1097/INF.0b013e31816b4539.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 21, 2007)	50
Original Actual Enrollment ICMJE	Same as current
Actual Study Completion Date	November 2008
Actual Primary Completion Date	November 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Confirmed HIV-1 infection by HIV-DNA PCR if < 18 months old or by HIV ELISA if greater than or equal to 18 months old; Subject is less than or equal to 16 years of age at the day of the first dosing.; Subject is failing a current NRTI and/or NNRTI containing regimen and is naïve to protease inhibitor containing therapy.; Results of biochemistry and haematology testing should be within pre-specified ranges.; Subject is able to swallow capsules; Caretaker(s) is/are able and willing to sign the Informed Consent Form prior to screening evaluations. Exclusion Criteria: History of sensitivity/idiosyncrasy to lopinavir, ritonavir, saquinavir or chemically related compounds or excipients which may be employed in the trial.; Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.; Inability of both child and caregiver(s) to understand the nature and extent of the trial and the procedures required.; Use of any of concomitant medication, including the drug listed below, that may interfere with the pharmacokinetics of LPV/r or SQV. NNRTIs Rifampicin Rifabutin Phenobarbital Phenytoine Carbamazepine Dexamethasone Ketoconazole Clarithromycin; Pregnancy
Sex/Gender	Sexes Eligible for Study: All
Ages	1 Year to 16 Years (Child)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Thailand
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00476359
Other Study ID Numbers ICMJE	HIV-NAT 017
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	The HIV Netherlands Australia Thailand Research Collaboration
Study Sponsor ICMJE	The HIV Netherlands Australia Thailand Research Collaboration
Collaborators ICMJE	Roche for trial and Saquinavir,and Abbott for Kaletra
Investigators ICMJE	Principal Investigator: Kiat Ruxrungtham, MD HIV-NAT, Bangkok, Thailand Principal Investigator: Pope Kosalaraksa, MD Khon Kaen University
PRS Account	The HIV Netherlands Australia Thailand Research Collaboration
Verification Date	March 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP