<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01715987</url>
  </required_header>
  <id_info>
    <org_study_id>BMS AI463-254</org_study_id>
    <nct_id>NCT01715987</nct_id>
  </id_info>
  <brief_title>Tubular Function in Asian-American Patients Receiving TDF or ETV for HBV Treatment</brief_title>
  <official_title>A Prospective and Open-Label Study of the Effect on Proximal Tubular Function in Asian-American Patients Receiving Tenofovir Disoproxil Fumarate (TDF) or Entecavir (ETV) for HBV Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New Discovery LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>New Discovery LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Nucleotide anti-viral analogues, including adefovir and TDF, have demonstrated kidney&#xD;
      toxicity in HIV/HBV co-infected patients and HBV mono-infected European patients.&#xD;
      Investigators suspected similar kidney proximal tubular injury can also occur in HBV mono&#xD;
      infected Asian patients receiving TDF treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to evaluate the safety use of ETV and TDF after at&#xD;
      least 144 weeks of treatment in terms of the effects of renal tubular function as determined&#xD;
      by (1) 24 hours Urine phosphate (wasting is &gt;1200 mg daily); (2) 24 hours&#xD;
      β2-microglobulinuria (NL β2-microglobulin level, &lt;1 mg daily); (3) fractional excretion of&#xD;
      uric acid, and (4) fractional tubular reabsorption of phosphorus.&#xD;
&#xD;
      The secondary objectives are to evaluate:&#xD;
&#xD;
        1. To evaluate compare the anti-viral effects of both TDF and ETV as determined the&#xD;
           percentage of patient who achieve HBV DNA levels below 60 IU/mL (by quantitative HBV DNA&#xD;
           PCR test with lowest level of detection at 60 IU/mL) and ALT normalization by routine&#xD;
           biochemical test after 144 weeks of treatment.&#xD;
&#xD;
        2. Serological responses including percentage of patients with HBeAg loss or seroconversion&#xD;
           and HBsAg loss or seroconversion with TDF and ETV treatment in Asian-American adults&#xD;
           with CHB infection.&#xD;
&#xD;
        3. To evaluate the three-year (one year treatment before enrollment and two year treatment&#xD;
           after enrollment) the percentage of patient with anti-HBV drug resistance of TDF and&#xD;
           ETV, including genotypic mutations in Asian-American adults with CHB.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>renal tubular dysfunction</measure>
    <time_frame>at 144 week after treatment with antiviral</time_frame>
    <description>renal tubular dysfunction as determined by (1) 24 hours Urine phosphate (wasting is &gt;1200 mg daily); (2) 24 hours β2-microglobulinuria (NL β2-microglobulin level, &lt;1 mg daily); (3) fractional excretion of uric acid, and (4) fractional tubular reabsorption of phosphorus.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">48</enrollment>
  <condition>Hepatitis B</condition>
  <arm_group>
    <arm_group_label>Tenofovir Disoproxil Fumarate</arm_group_label>
    <description>Patients who are taking Tenofovir Disoproxil Fumarate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Entecavir</arm_group_label>
    <description>Patients who are taking Entecavir.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir Disoproxil Fumarate</intervention_name>
    <description>300mg, oral daily for two years</description>
    <arm_group_label>Tenofovir Disoproxil Fumarate</arm_group_label>
    <other_name>Viread</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entecavir</intervention_name>
    <description>0.5mg oral daily for two years.</description>
    <arm_group_label>Entecavir</arm_group_label>
    <other_name>Baraclude</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood Urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Asian Americans with hepatitis B taking Entecavir or Tenofovir.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-70 year-old Asian-American male or female patients with HBeAg+ or HBeAg-CHB&#xD;
&#xD;
          -  On TDF or ETV mono-therapy for 12-24 months, not previously exposed to other oral HBV&#xD;
             drugs, nor received any type of interferon treatment in the past 12 months&#xD;
&#xD;
          -  Be willing to participate&#xD;
&#xD;
          -  Continuation of HBV treatment is medically indicated. That is for HBeAg-positive&#xD;
             subjects, HBeAg remain positive or HBeAg becomes negative but still has detectable DNA&#xD;
             by the PCR method; and for HBeAg-negative subjects, HBV DNA is either detectable or&#xD;
             undetectable by the PCR method&#xD;
&#xD;
          -  No clinical or virologic evidence of anti-HBV resistance to TDF treatment at the time&#xD;
             of entering tests&#xD;
&#xD;
          -  Serum creatinine &lt; 1.5 mg/L and estimated glomerular filtration rate (creatinine&#xD;
             clearance) ≥ 60 mL/min/1.73m2 by the Cockcroft-Gault equation:&#xD;
&#xD;
             (140-age in years)(body weight [kg] )/((72)(serum creatinine [mg/dl]) ) [Note:&#xD;
             multiply estimated rate 0. by 85 for women; use actual body weight]&#xD;
&#xD;
          -  Adequate hematologic function (absolute neutrophil count ≥ 1,500/mm3; hemoglobin ≥&#xD;
             10.0 g/dL)&#xD;
&#xD;
          -  To assure all the subjects will be regularly followed per study protocol and minimize&#xD;
             the drop off rate, the subjects have to have documented pre-treatment full evaluation&#xD;
             and necessary blood tests, medical adherence to HBV treatment, and regular follow-up&#xD;
             (i.e., on HBV treatment not missing HBV medication (TDF or ETV) for more than a week,&#xD;
             with medical follow-up for HBV treatment at least every 6 month and had all the&#xD;
             necessary labs performed.&#xD;
&#xD;
          -  In the absence of exclusion criteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Ethnicity: Non-Asian CHB patients&#xD;
&#xD;
          -  Age: &gt;70 years old&#xD;
&#xD;
          -  Body weight and height: BMI ≥ 30&#xD;
&#xD;
          -  Concomitant nephrotoxic agents - record all prescription and nonprescription items&#xD;
             including herbs and natural remedies, NSAIDs, acyclovir, statins, ACEI or ARBs,&#xD;
             Valproate&#xD;
&#xD;
          -  Any other antiretroviral meds, antibiotic exposure during study to be noted&#xD;
&#xD;
          -  History of HCV, HDV, or HIV co-infection&#xD;
&#xD;
          -  Prior history of clinical hepatic decompensation defined as direct (conjugated)&#xD;
             bilirubin ≥ 1.2 ULN; PT ≥ 1.2 ULN, platelets ≤ 50,000/mm3, or serum albumin ≤ 3.5&#xD;
             g/dL, ascites, jaundice, encephalopathy, or variceal hemorrhage&#xD;
&#xD;
          -  Serum α-fetoprotein ≥ 50 ng/mL&#xD;
&#xD;
          -  Evidence of hepatocellular carcinoma (HCC)&#xD;
&#xD;
          -  History of solid organ or bone marrow transplantation&#xD;
&#xD;
          -  History of malignancies in the past 5 years&#xD;
&#xD;
          -  Pregnant women, and women who are breast feeding or who believe they may wish to&#xD;
             become pregnant during the course of the study.&#xD;
&#xD;
          -  Males and females of reproductive potential who are not willing to use an effective&#xD;
             method of contraception during the study. For males, condoms should be used and for&#xD;
             females, a barrier contraception method should be used in combination with one other&#xD;
             form of contraception.&#xD;
&#xD;
          -  History of significant renal disease&#xD;
&#xD;
          -  History of significant bone disease&#xD;
&#xD;
          -  History of HTN or DM on medical treatment&#xD;
&#xD;
          -  Ongoing therapy with any of the following:&#xD;
&#xD;
               1. Nephrotoxic agents&#xD;
&#xD;
               2. Parenteral aminoglycoside antibiotics&#xD;
&#xD;
               3. Cidofovir&#xD;
&#xD;
               4. Cisplatin&#xD;
&#xD;
               5. Foscarnet&#xD;
&#xD;
               6. IV amphotericin B&#xD;
&#xD;
               7. IV pentamidine&#xD;
&#xD;
               8. Oral or IV ganciclovir&#xD;
&#xD;
               9. Cyclosporine&#xD;
&#xD;
              10. Tacrolimus&#xD;
&#xD;
              11. IV vancomycin&#xD;
&#xD;
              12. Chronic daily non-steroidal anti-inflammatory drug therapy&#xD;
&#xD;
              13. Competitors of renal excretion Systemic chemotherapeutic agents&#xD;
&#xD;
              14. Systemic corticosteroids&#xD;
&#xD;
              15. Interleukin-2 (IL-2) and other immunomodulating agents&#xD;
&#xD;
          -  Investigational agents (except with the expressed approval of the lead investigators)&#xD;
             Administration of any of the above medications must be discontinued at least 30 days&#xD;
             prior to the Baseline Visit and for the duration of the study period.&#xD;
&#xD;
               1. Known hypersensitivity to the study drugs, the metabolites or formulation&#xD;
                  excipients&#xD;
&#xD;
               2. Any other condition (including alcohol or substance abuse) or prior therapy that,&#xD;
                  in the opinion of the Investigators, would make the subject unsuitable for the&#xD;
                  study or unable to comply with dosing requirements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Calvin Q Pan, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mount Sinai School of Medicine, New York</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Asian Pacific Liver Center at St. Vincent Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Discovery LLC</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>11355</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>October 23, 2012</study_first_submitted>
  <study_first_submitted_qc>October 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>September 5, 2017</last_update_submitted>
  <last_update_submitted_qc>September 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatitis B</keyword>
  <keyword>Antiviral</keyword>
  <keyword>Tubular dysfunction</keyword>
  <keyword>Entecavir</keyword>
  <keyword>Tenofovir</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Entecavir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01715987
org study id: BMS AI463-254
nct id: NCT01715987
lead sponsor: 
has dmc: No
Nucleotide anti-viral analogues, including adefovir and TDF, have demonstrated kidney
      toxicity in HIV/HBV co-infected patients and HBV mono-infected European patients.
      Investigators suspected similar kidney proximal tubular injury can also occur in HBV mono
      infected Asian patients receiving TDF treatment.
The primary objective of this study is to evaluate the safety use of ETV and TDF after at
      least 144 weeks of treatment in terms of the effects of renal tubular function as determined
      by (1) 24 hours Urine phosphate (wasting is >1200 mg daily); (2) 24 hours
      β2-microglobulinuria (NL β2-microglobulin level, <1 mg daily); (3) fractional excretion of
      uric acid, and (4) fractional tubular reabsorption of phosphorus.

      The secondary objectives are to evaluate:

        1. To evaluate compare the anti-viral effects of both TDF and ETV as determined the
           percentage of patient who achieve HBV DNA levels below 60 IU/mL (by quantitative HBV DNA
           PCR test with lowest level of detection at 60 IU/mL) and ALT normalization by routine
           biochemical test after 144 weeks of treatment.

        2. Serological responses including percentage of patients with HBeAg loss or seroconversion
           and HBsAg loss or seroconversion with TDF and ETV treatment in Asian-American adults
           with CHB infection.

        3. To evaluate the three-year (one year treatment before enrollment and two year treatment
           after enrollment) the percentage of patient with anti-HBV drug resistance of TDF and
           ETV, including genotypic mutations in Asian-American adults with CHB.
observational model: Case-Control
time perspective: Prospective
measure: renal tubular dysfunction
time frame: at 144 week after treatment with antiviral
description: renal tubular dysfunction as determined by (1) 24 hours Urine phosphate (wasting is >1200 mg daily); (2) 24 hours β2-microglobulinuria (NL β2-microglobulin level, <1 mg daily); (3) fractional excretion of uric acid, and (4) fractional tubular reabsorption of phosphorus.
arm group label: Tenofovir Disoproxil Fumarate
description: Patients who are taking Tenofovir Disoproxil Fumarate.
arm group label: Entecavir
description: Patients who are taking Entecavir.
intervention type: Drug
intervention name: Tenofovir Disoproxil Fumarate
description: 300mg, oral daily for two years
arm group label: Tenofovir Disoproxil Fumarate
other name: Viread
intervention type: Drug
intervention name: Entecavir
description: 0.5mg oral daily for two years.
arm group label: Entecavir
other name: Baraclude
Blood Urine
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Calvin Q Pan, M.D.
role: Principal Investigator
affiliation: Mount Sinai School of Medicine, New York
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hepatitis B
mesh term: Hepatitis
mesh term: Tenofovir
mesh term: Entecavir