<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/NCT01721993</url>
  </required_header>
  <id_info>
    <org_study_id>THAR2011-1</org_study_id>
    <nct_id>NCT01721993</nct_id>
  </id_info>
  <brief_title>Open Label Dose Escalation Phase I Study to Investigate the Safety and Pharmacokinetics of T121E01F and T121E02F in Healthy Postmenopausal Women</brief_title>
  <official_title>Open Label Dose Escalation Phase I Study to Investigate the Safety and Pharmacokinetics of T121E01Fand T121E02F in Healthy Postmenopausal Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thar Pharmaceuticals, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Thar Pharmaceuticals, Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      THAR2011-1 is a Phase I, single dose, open-label dose-escalation study to determine the&#xD;
      safety, absolute bioavailability, dose proportionality, and pharmacokinetics of T121 in&#xD;
      healthy postmenopausal women. The study is expected to identify a safe dose that can be&#xD;
      further tested in subsequent multiple dose studies comparing the safety, PK and&#xD;
      pharmacodynamics (PD) of T121 with the currently marketed IV zoledronic acid (Zometa).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PK parameters for a single dose of T121E01F, T121E02F or Zometa and assessment of dose proportionality for T121E01F</measure>
    <time_frame>48 hours</time_frame>
    <description>Pharmacokinetic parameters will include maximum serum concentration (Cmax), time corresponding to the occurrence of maximum serum concentration (tmax), area under the serum concentration-time curve from zero to the last observed quantifiable concentration (AUCtlast), area under the serum concentration-time curve from time zero to infinity (AUC), terminal exponential half-life (t1/2,z), absolute bioavailability, cumulative amount recovered in urine (Ae) and renal clearance (CLr).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of T121E01F and T121E02F</measure>
    <time_frame>7 Days</time_frame>
    <description>Safety will be assessed by the number and severity of adverse events (AE) and changes in clinical laboratory safety parameters and vital signs from pre to post dose in each dose group. The frequency, severity and type of AEs between the dose groups will also be assessed. AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.03; June 14, 2010).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">71</enrollment>
  <condition>Healthy Postmenopausal Women</condition>
  <arm_group>
    <arm_group_label>T121E01F</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>zoledronic acid IV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>T121</intervention_name>
    <arm_group_label>T121E01F</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zoledronic acid</intervention_name>
    <arm_group_label>zoledronic acid IV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy, postmenopausal women between the ages of 35 and 70 years, inclusive.&#xD;
             Postmenopausal females (based on medical history) defined as 12 continuous months of&#xD;
             spontaneous amenorrhea or bilateral oophorectomy. Women 60 years of age and older will&#xD;
             be considered postmenopausal. Women 35-59 must have a serum follicle-stimulating&#xD;
             hormone (FSH) result consistent with postmenopausal state.&#xD;
&#xD;
          -  Body Mass Index (BMI) of 17.5 to 32 kg/m2; and a total body weight &gt;50 kg (110 lbs)&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or&#xD;
             allergic disease.&#xD;
&#xD;
          -  History of any severe allergic reaction or known allergy to ZA.&#xD;
&#xD;
          -  Evidence or history of any gastrointestinal disease, such as irritable bowel syndrome,&#xD;
             Crohn's Disease, chronic gastritis, peptic ulcer disease, H. pylori infection, or&#xD;
             other gastrointestinal condition possibly affecting drug absorption.&#xD;
&#xD;
          -  History of gastric surgery, including the Roux-en-Y gastric bypass surgery or an&#xD;
             antrectomy with vagotomy, or gastrectomy.&#xD;
&#xD;
          -  Evidence or history of any clinically significant cardiovascular (CV) disease or&#xD;
             condition, including:&#xD;
&#xD;
               -  Any history of a major CV event (myocardial infarction, unstable angina,&#xD;
                  cerebrovascular accident, transient ischemic attack);&#xD;
&#xD;
               -  Any history of a significant cardiac arrhythmia, implanted artificial pacemaker;&#xD;
&#xD;
               -  Blood pressure greater than 150/90 and heart rate greater than 100 at screening;&#xD;
&#xD;
               -  Clinically significant abnormalities on 12-lead ECG, including QTc &gt;450 msec&#xD;
                  (heart-rate corrected using the Fridericia formula) at Screening.&#xD;
&#xD;
          -  History of any autoimmune disease (e.g., systemic lupus erythematosus [SLE],&#xD;
             scleroderma, psoriasis, vitiligo, primary biliary cirrhosis, etc.).&#xD;
&#xD;
          -  Active/ongoing endocrine disorders (e.g., type 1 diabetes, adrenal insufficiency,&#xD;
             hypoparathyroidism, etc.) except well controlled thyroid disease and type II diabetes&#xD;
             with HgbA1C &lt;8 are permitted.&#xD;
&#xD;
          -  Mucolipidosis type IV.&#xD;
&#xD;
          -  Any clinically significant hematological condition (e.g., pernicious anemia).&#xD;
&#xD;
          -  Evidence or history of any other severe acute or chronic medical (including renal,&#xD;
             pulmonary, hepatic, neurologic, psychiatric, etc.) disease or condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or&#xD;
             investigational product administration, or may interfere with the interpretation of&#xD;
             study results and, in the judgment of the investigator, would make the subject&#xD;
             inappropriate for entry into this study.&#xD;
&#xD;
          -  History or evidence of Paget's disease of bone (osteitis deformans) or related&#xD;
             disorder.&#xD;
&#xD;
          -  A positive urine drug screen.&#xD;
&#xD;
          -  A positive pregnancy test.&#xD;
&#xD;
          -  History of difficulty swallowing large pills/tablets.&#xD;
&#xD;
          -  Active dental or oral disease that would increase risk of bisphosphonate use and/or&#xD;
             requires dental care.&#xD;
&#xD;
          -  Prohibited substance use, including:&#xD;
&#xD;
               -  Any documented history of drug or alcohol abuse within the previous 10 years;&#xD;
&#xD;
               -  Chronic consumption over the past 12 months of more than 2 standard units per day&#xD;
                  of alcohol (a standard unit equals 12 ounces of beer, 1 ½ ounces of 80-proof&#xD;
                  alcohol or 6 ounces of wine);&#xD;
&#xD;
               -  Subject reported tobacco or nicotine use within 30 days of admission.&#xD;
&#xD;
          -  Prohibited medication use, including:&#xD;
&#xD;
               -  Treatment with an investigational drug within 30 days (or as determined by the&#xD;
                  local requirement, whichever is longer) or 5 half-lives preceding the first dose&#xD;
                  of study medication, whichever is longer;&#xD;
&#xD;
               -  Use of nonprescription drugs and dietary and/or vitamin supplements within 7 days&#xD;
                  prior to the first dose of study medication. Use of acetaminophen is acceptable&#xD;
                  for management of acute (e.g., pain) condition, as long as the daily dose is &lt;&#xD;
                  2000 mg and the duration does not exceed 3 consecutive days. The need for other&#xD;
                  new prescription or non-prescription drug(s) or supplements during the study&#xD;
                  should be discussed with the Medical Monitor;&#xD;
&#xD;
               -  Prescription or herbal supplements within 14 days prior to the first dose of&#xD;
                  study medication;&#xD;
&#xD;
               -  History of chronic proton pump inhibitor (PPI) use Proton pump inhibitors, H2&#xD;
                  blockers, hormone replacement therapy, aminoglycosides, loop diuretics and&#xD;
                  nephrotoxic drugs within 30 days prior to the first dose of study medication;&#xD;
&#xD;
               -  Bisphosphonate use within 90 days prior to the first dose of study medication;&#xD;
&#xD;
               -  Use of a non-steroidal anti-inflammatory drug (NSAID) within 7 days prior to and&#xD;
                  7 days after the administration of study medication;&#xD;
&#xD;
               -  Use of acid reducer medication - including any antacid component, both&#xD;
                  non-prescription and prescription, within 7 days prior to and 1 day after the&#xD;
                  administration of study medication;&#xD;
&#xD;
               -  Use of loop diuretics.&#xD;
&#xD;
          -  A positive serology for Hepatitis B, Hepatitis C, HIV, or H. pylori. An indeterminate&#xD;
             H. pylori result must be confirmed with an H. Pylori breath test. A positive result is&#xD;
             exclusionary.&#xD;
&#xD;
          -  Any invasive dental or oral procedure completed within 30 days prior to the first dose&#xD;
             of study medication or anticipated during the study or within 30 days of completion of&#xD;
             the study.&#xD;
&#xD;
          -  Clinically significant abnormal laboratory test values, as determined by the&#xD;
             Investigator, or any of the following:&#xD;
&#xD;
               -  alanine aminotransferase (ALT), aspartate aminotransferase (AST), or creatinine&#xD;
                  1.5 times above the upper limit of normal (ULN);&#xD;
&#xD;
               -  platelets below the lower limit of normal;&#xD;
&#xD;
               -  hemoglobin 10% below the lower level of normal;&#xD;
&#xD;
               -  any out of normal range values for serum sodium, serum calcium, serum potassium&#xD;
                  or serum magnesium;&#xD;
&#xD;
               -  Glomerular filtration rate (eGFR) &lt; 60 mL/ minute as calculated by the modified&#xD;
                  Modification of Diet in Renal Disease (MDRD) formula.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark A Matson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Prism Clinical Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prism Clinical Research</name>
      <address>
        <city>St. Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>March 25, 2015</last_update_submitted>
  <last_update_submitted_qc>March 25, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 26, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>oral zoledronic acid</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Zoledronic Acid</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/NCT01721993
org study id: THAR2011-1
nct id: NCT01721993
lead sponsor: 
has dmc: Yes
THAR2011-1 is a Phase I, single dose, open-label dose-escalation study to determine the
      safety, absolute bioavailability, dose proportionality, and pharmacokinetics of T121 in
      healthy postmenopausal women. The study is expected to identify a safe dose that can be
      further tested in subsequent multiple dose studies comparing the safety, PK and
      pharmacodynamics (PD) of T121 with the currently marketed IV zoledronic acid (Zometa).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: PK parameters for a single dose of T121E01F, T121E02F or Zometa and assessment of dose proportionality for T121E01F
time frame: 48 hours
description: Pharmacokinetic parameters will include maximum serum concentration (Cmax), time corresponding to the occurrence of maximum serum concentration (tmax), area under the serum concentration-time curve from zero to the last observed quantifiable concentration (AUCtlast), area under the serum concentration-time curve from time zero to infinity (AUC), terminal exponential half-life (t1/2,z), absolute bioavailability, cumulative amount recovered in urine (Ae) and renal clearance (CLr).
measure: Safety and Tolerability of T121E01F and T121E02F
time frame: 7 Days
description: Safety will be assessed by the number and severity of adverse events (AE) and changes in clinical laboratory safety parameters and vital signs from pre to post dose in each dose group. The frequency, severity and type of AEs between the dose groups will also be assessed. AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.03; June 14, 2010).
arm group label: T121E01F
arm group type: Experimental
arm group label: zoledronic acid IV
arm group type: Active Comparator
intervention type: Drug
intervention name: T121
arm group label: T121E01F
intervention type: Drug
intervention name: Zoledronic acid
arm group label: zoledronic acid IV
criteria: 
gender: Female
minimum age: 35 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mark A Matson, MD
role: Principal Investigator
affiliation: Prism Clinical Research
facility: 
country: United States
responsible party type: Sponsor
mesh term: Zoledronic Acid