Clinical trial NCT01671982: ALternative TEnofovir Dosing in Adults With Moderate Renal Function Impairment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: The Government Pharmaceutical Organization
name: Chiang Mai University
First posted: 2012-08-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Tenofovir plasma area-under the concentration time curve (AUC)
timeFrame: Study Entry and Day 14
Secondary outcomes:
Other outcomes:
Locations:
city: Sanpatong
country: Thailand
facility: Sanpatong Hospital
state: Chiang Mai
city: Bangkok
country: Thailand
facility: HIV-NAT
city: Chiang Mai
country: Thailand
facility: Nakornping Hospital
city: Chonburi
country: Thailand
facility: Chonburi Hospital
city: Phayao
country: Thailand
facility: Phayao Hospital
Study officials:
affiliation: PHPT / Chiang Mai University / IRD
name: Tim R Cressey, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Hours vs 150 mg Once Daily in HIV-Infected Adults With Moderate Renal Function Impairment. Clin Infect Dis. 2015 Aug 15;61(4):633-9. doi: 10.1093/cid/civ346. Epub 2015 Apr 28.