ALternative TEnofovir Dosing in Adults With Moderate Renal Function Impairment (ALTER)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The Government Pharmaceutical Organization
Chiang Mai University
Information provided by (Responsible Party):
Gonzague Jourdain, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT01671982
First received: August 17, 2012
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
HIV
Other: Tenofovir Dose Adjustment
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • Tenofovir plasma area-under the concentration time curve (AUC) [ Time Frame: Study Entry and Day 14 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 40
Study Start Date: August 2012
Estimated Study Completion Date: September 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tenofovir-containing HAART 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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01671982

Locations
Thailand
Sanpatong Hospital
Sanpatong, Chiang Mai, Thailand, 20120
HIV-NAT
Bangkok, Thailand, 10330
Nakornping Hospital
Chiang Mai, Thailand
Chonburi Hospital
Chonburi, Thailand, 20000
Phayao Hospital
Phayao, Thailand, 56000
Sponsors and Collaborators
Institut de Recherche pour le Developpement
The Government Pharmaceutical Organization
Chiang Mai University
Investigators
Principal Investigator: Tim R Cressey, PhD PHPT / Chiang Mai University / IRD
  More Information

Additional Information:
No publications provided

Responsible Party: Gonzague Jourdain, Director, International Reserach Unit 174, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT01671982     History of Changes
Other Study ID Numbers: ALTER
Study First Received: August 17, 2012
Last Updated: February 17, 2014
Health Authority: Thailand: Ministry of Public Health

Additional relevant MeSH terms:
Reverse Transcriptase Inhibitors
Tenofovir
Tenofovir disoproxil
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on October 19, 2014