Clinical trial NCT00476359: A PK and Salvage Study for Children With HIV-infection
Official title: Lopinavir/r Plus Saquinavir Salvage Therapy in HIV-infected Children With NRTI and/or NNRTI Failure: PK and Two-year Treatment Follow up
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Lopinavir/r
Saquinavir
Dual boosted PIs
Pharmacokinetics
HIV children
C min
Second line HAART
ARV
VL failure
Dosage
To evaluate treatment response
Treatment Experienced
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Roche for trial and Saquinavir,and Abbott for Kaletra
First posted: 2007-05-22
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Subject is less than or equal to 16 years of age at the day of the first dosing.
3. Subject is failing a current NRTI and/or NNRTI containing regimen and is naïve to protease inhibitor containing therapy.
4. Results of biochemistry and haematology testing should be within pre-specified ranges.
5. Subject is able to swallow capsules
6. Caretaker(s) is/are able and willing to sign the Informed Consent Form prior to screening evaluations.

Exclusion Criteria:

1. History of sensitivity/idiosyncrasy to lopinavir, ritonavir, saquinavir or chemically related compounds or excipients which may be employed in the trial.
2. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
3. Inability of both child and caregiver(s) to understand the nature and extent of the trial and the procedures required.
4. 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
5. Pregnancy

Primary outcomes:
measure: Intensive 0-12h PK sampling for plasma levels of LPV and SQV, and blood sampling. CD4 viral load safety lab every 3 months.
timeFrame: 96 week
Secondary outcomes:
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Chulalongkorn University Hospital, Department of Pediatrics
city: Bangkok
country: Thailand
facility: The HIV Netherlands Australia Thailand Research Collaboration
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
Study officials:
affiliation: HIV-NAT, Bangkok, Thailand
name: Kiat Ruxrungtham, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Khon Kaen University
name: Pope Kosalaraksa, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1097/01.inf.0000180578.38584.da.
citation: 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
citation: 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.
citation: 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.
citation: 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.
citation: 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.