ALternative TEnofovir Dosing in Adults With Moderate Renal Function Impairment

HIV Clinical Trial

— ALTER  

Official title:

Tenofovir Pharmacokinetics in HIV-infected Thai Adults With Moderate Renal Function Impairment Receiving Either a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based or Lopinavir/Ritonavir-based Antiretroviral Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01671982
• Other study ID #: ALTER
• Status: Completed
• Phase: Phase 1
• Start date: August 2012
• Est. completion date: May 2015

Study information

• Verified date: October 2023
• Source: Institut de Recherche pour le Developpement
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess the drug concentrations of tenofovir (TDF) in HIV-infected Thai adults with moderate renal function impairment when administered at the recommended dose of 300 mg every 48 hours, and at an alternative dose of 150 mg every 24 hours.

Description:

The study is designed as a Phase I, non-randomized, open-label, pharmacokinetic study. We hypothesize that administration of tenofovir 150 mg once daily to HIV-infected Thai adults with moderate renal function impairment (CLcr between 30 to <50 mL/min) will provide comparable drug exposure to the current recommended dose of 300 mg every 48 hours.

Confirmed HIV-positive subjects receiving tenofovir (TDF) 300 mg, every 48 hours, as part of an NNRTI-based or lopinavir/ritonavir (LPV/r)-based HAART regimen will be proposed to participate.

Subjects meeting the required criteria will be enrolled into one of 2 groups depending on their HAART regimen: .

Group 1: Subjects receiving tenofovir 300 mg, every 48 hours, in combination with lamivudine and an NNRTI,and a confirmed CLcr 30 to <50 mL/min

Group 2: Subjects receiving tenofovir 300 mg, every 48 hours, in combination with lamivudine and lopinavir/ritonavir, and a confirmed CLcr 30 to <50 mL/min

The study procedures are identical for both groups. All subjects enrolled will have two study visits. At the first visit, a 48-hour pharmacokinetic evaluation will be performed. Immediately following completion of the PK sampling, the tenofovir dose will be changed to 150 mg, once daily. Two weeks later, at the second visit, a 24-hour pharmacokinetic evaluation will be performed. Following completion of the second PK sampling the tenofovir dose will be changed back to 300 mg every 48 hours. At this time the subjects has reach the end of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2015
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• age >18 years old

• provided written informed consent

• receiving the tenofovir tablet formulation from the Thai Government Pharmaceutical Organization (GPO) for at least 4 weeks before enrollment

• documentation of confirmed HIV-1 infection (documented by two serology tests obtained at two different dates)

• Confirmed Creatinine clearance result between 30 to <50 mL/min [confirmed defined as two CLcr determinations calculated using the Cockcroft-Gault equation within two weeks of each other, within 1 month prior to entry]

• received tenofovir 300 mg, every 48 hours for at least 2 weeks prior to entry, in combination with 3TC plus NNRTI, or 3TC plus lopinavir/ritonavir

• a HIV-1 RNA viral load < 50 copies/mL within 6 months prior to entry

Exclusion Criteria:

• Concomitant use of a atazanavir, didanosine

• Pregnant

• Any of the following laboratory tests within 30 days prior to study entry classified as = Grade 3 (see DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0 [Dec. 2004], Clarification August, 2009): neutrophil count, hemoglobin, platelets, AST, or ALT

• HBs-antigen positive

• Any clinically significant diseases (other than HIV-1 infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise participation in this study

• concurrent participation to any other clinical trial without prior agreement of the two study teams

Related Conditions & MeSH terms

• HIV

Intervention

Other:
• Tenofovir Dose Adjustment
In subjects with a confirmed CLcr 30 to <50 mL/min, switch tenofovir 300 mg every 48 hours, to 150 mg once daily for 2 weeks.

Locations

Country	Name	City	State
Thailand	HIV-NAT	Bangkok
Thailand	Nakornping Hospital	Chiang Mai
Thailand	Chonburi Hospital	Chonburi
Thailand	Phayao Hospital	Phayao
Thailand	Sanpatong Hospital	Sanpatong	Chiang Mai

Sponsors (3)

Lead Sponsor	Collaborator
Institut de Recherche pour le Developpement	Chiang Mai University, The Government Pharmaceutical Organization

Country where clinical trial is conducted

Thailand, 

References & Publications (1)

Cressey TR, Avihingsanon A, Halue G, Leenasirimakul P, Sukrakanchana PO, Tawon Y, Jaisieng N, Jourdain G, Podany AT, Fletcher CV, Klinbuayaem V, Bowonwatanuwong C. Plasma and Intracellular Pharmacokinetics of Tenofovir Disoproxil Fumarate 300 mg Every 48 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tenofovir plasma area-under the concentration time curve (AUC)	For each patient, ratios of AUC0-last of q24h versus q48h will be calculated. Geometric mean ratios (GMRs) with 90% CI will be calculated after log-transformation of within patient ratios.	Study Entry and Day 14

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