PK TDF in Thai HIV-infected Children

Pharmacokinetics Study of Tenofovir in HIV-infected Thai Children Using Tenofovir-based Regimen

This study will assess the pharmacokinetics of TDF in Thai HIV-infected children

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Efavirenz; Drug: TDF (Tenofovir); Drug: lopinavir/ritonavir, atazanavir/ritonavir

Detailed Description

HIV-infected children who are currently on TDF-base once daily regimen will be enrolled into this study. PK visit will be performed at least 1 month after changing regimen to once daily regimen. Adherence 3 days before PK study will be confirmed using adherence questionnaire. 100% of adherence is needed for PK study. If there is adherence problem on PK visit, PK study will be deferred to at least 3 days. On PK visit, blood drawn will be performed at 0, 2, 4, 6, 8, 10, 12, 24 hr. after taking ARVs for PK study. Blood drawn for safety evaluation will be drawn at any time-point on the PK visit. There is no study drug in this study. All ARVs that patient taking will be according to patient's requirement, and physician judgment. ARVs dosage will follow the Thai national pediatric guideline. CBC, CD4, viral RNA, viral resistance, ALT, cholesterol, and triglyceride results can be from other visits within 4 weeks window period.

Statistical considerations Sample size calculations. There are no pharmacokinetic data in children. In adults, the mean (SD) AUC following administration of a 300mg Viread tablet in fasting state is 2.29 (0.69) microg.hr/mL. In patients taking lopinavir/ritonavir and atazanavir/ritonavir, the mean AUC of TDF is increased by 32% and 24% respectively. Efavirenz does not change the AUC of TDF. If the weight adjusted dose of TDF in children and adolescents achieves the same AUC as in adults and concomitant dosing with a protease inhibitor increases the TDF AUC by 30% but concomitant dosing with Efavirenz does not change the TDF AUC, then 20 treated with Efavirenz and 20 patients treated on a PI based regimen would provide 90% power to detect this difference at the 5% significance level.

Statistical Analysis.

Primary endpoints Pharmacokinetic parameters will be calculated based on individual plasma concentration vs time data, using noncompartmental methods. Data will be summarized overall and by whether the patient is taking a PI or an EFV-based regimen. Formal statistical comparisons of parameters will be made using ANOVA techniques or non-parametric equivalents as appropriate. Effect sizes and 95% confidence intervals will be given for all comparisons.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Khon Kaen, Thailand, 40002
    • Khon Kaen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• children between the ages of 8-18 years with documented HIV infection
• currently on TDF once daily regimen
• have signed the informed consent

Exclusion Criteria:

• the child or care taker refuse to participate in the study
• severity of adverse events is more than grade 3 thirty days before participating in the study

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: non-nucleoside reverse transcriptase inhibitor (NNRTI); Efavirenz	Drug: Efavirenz; Drug: TDF (Tenofovir)
Other: ritonavir-boosted protease inhibitor; lopinavir/ritonavir atazanavir/ritonavir	Drug: TDF (Tenofovir); Drug: lopinavir/ritonavir, atazanavir/ritonavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
area under the curve (AUC) (pharmacokinetics of TDF)	pharmacokinetics of TDF in children between the ages of 8-18 years	12 months

Collaborators and Investigators

• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration
• Collaborators: Chulalongkorn University; Khon Kaen University
• Investigators: Principal Investigator: Thanyawee Puthanakit, MD, HIV-NAT and Chulalongkorn University

Publications and helpful links

Helpful Links

• HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)'s website

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: February 7, 2013
• First Submitted That Met QC Criteria: March 30, 2015
• First Posted (Estimate): March 31, 2015

Study Record Updates

• Last Update Posted (Estimate): March 31, 2015
• Last Update Submitted That Met QC Criteria: March 30, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: pharmacokinetics; Thai; TDF; HIV-infected children; non-nucleoside reverse transcriptase inhibitor (NNRTI); ritonavir-boosted protease inhibitor (bPI); less than eighteen years old
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Ritonavir; Lopinavir; Atazanavir Sulfate; Efavirenz
• Other Study ID Numbers: HIV-NAT 131