<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/NCT02208973</url>
  </required_header>
  <id_info>
    <org_study_id>IIBSP-PBF-2014-04</org_study_id>
    <secondary_id>2014-000425-20</secondary_id>
    <nct_id>NCT02208973</nct_id>
  </id_info>
  <brief_title>Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of PBF-680 After Multiple Oral Doses&quot;</brief_title>
  <official_title>Randomized, Double Blind, Placebo Controlled, Parallel Groups Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of PBF-680 &quot;After Multiple Oral Doses&quot; in Healthy Volunteers.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Palo Biofarma, S.L</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the safety and tolerability of five doses of PBF-680 (5 mg, 10 mg, 20 mg, 40 mg and&#xD;
      60mg) after repeated (8 days) single daily oral dose administration in young male and female&#xD;
      healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Serious and Non-Serious Adverse Events</measure>
    <time_frame>from day 0 to day 15</time_frame>
    <description>Vital Signs, ECG recordings, laboratory safety test and phisical examination will be performed</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Profile Analysis (Plasma concentrations)</measure>
    <time_frame>from day 1 to day 8</time_frame>
    <description>Day 1: baseline [pre-dose], [+10 min], [+20 min], [+40min], [+60min], [+ 1.5h], [+2 h], [+ 2.5 h], [+ 3 h], [+ 4h], [+8h], [+ 12h] and [+16h] post-medication;&#xD;
Days 2 to 7: baseline [daily pre-dose] which corresponds at +24h of previous dose;&#xD;
Day 8: baseline [daily pre-dose], [+10 min], [+20 min], [+40min], [+60min], [+1.5h], [+2 h], [+ 2.5 h], [+ 3 h], [+ 4h], [+8h], [+ 12h] and [+16h] and [+ 24h] post-daily medication (D9).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adenosine A1 receptor antagonism activity</measure>
    <time_frame>day 1 and day 8</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Leeds Sleep Evaluation Questionnaire</measure>
    <time_frame>from day 1 to day 8</time_frame>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>PBF-680 (5 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5 mg of PBF-680</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PBF-680 (10 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg of PBF-680</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PBF-680 (20 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 mg of PBF-680</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PBF-680 (40 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>40 mg of PBF-680</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PBF-680 (60 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 mg of PBF-680</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Comparator to the doses of 5, 10, 20, 40 and 60 mg. ( subjects for each dose level 6 are located to active treatment and two to placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PBF-680</intervention_name>
    <description>5, 10, 20, 40 and 60 mg of PBF-680</description>
    <arm_group_label>PBF-680 (10 mg)</arm_group_label>
    <arm_group_label>PBF-680 (20 mg)</arm_group_label>
    <arm_group_label>PBF-680 (40 mg)</arm_group_label>
    <arm_group_label>PBF-680 (5 mg)</arm_group_label>
    <arm_group_label>PBF-680 (60 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo for the dose of 5, 10, 20 and 40 mg of PBF-680</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects meeting all the following inclusion criteria at screening visit:&#xD;
&#xD;
               1. Healthy male or females subjects, 18-45 years (inclusive) of age at the time of&#xD;
                  enrollment.&#xD;
&#xD;
               2. Females must be of non-childbearing potential (i.e., surgically sterile) or have&#xD;
                  to use contraceptive measures (non-hormonal) such as condom, diaphragm or&#xD;
                  cervical/vault cap with spermicide until 28 days post-administration. Males&#xD;
                  should agree to abstain from sexual intercourse with a female partner or agree to&#xD;
                  use a condom with spermicide, in addition to having their female partner use some&#xD;
                  contraceptive measures until 28 days post-administration.&#xD;
&#xD;
               3. Clinically acceptable blood pressure and pulse rate in supine and standing&#xD;
                  position. Blood pressure and pulse will be measured after a minimum of 3 minutes&#xD;
                  of resting.&#xD;
&#xD;
               4. Body weight within normal range (Quetelet's index between 19 and 26) expressed as&#xD;
                  weight (kg) / height (m2).&#xD;
&#xD;
               5. Able to understand the nature of the study and comply with all their&#xD;
                  requirements.&#xD;
&#xD;
               6. Free acceptance to participate in the study by obtains signed informed consent&#xD;
                  form approved by the Ethics Committee of the Hospital (CEIC).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects meeting any of the following criteria at screening visit will be excluded&#xD;
             from entry into the study:&#xD;
&#xD;
               1. History of serious adverse reactions or hypersensitivity to any drug.&#xD;
&#xD;
               2. Presence or history of allergies requiring acute or chronic treatment (except&#xD;
                  seasonal allergic rhinitis).&#xD;
&#xD;
               3. Background or clinical evidence of chronic diseases.&#xD;
&#xD;
               4. Acute illness two weeks before drug administration.&#xD;
&#xD;
               5. Having undergone major surgery during the previous 6 months.&#xD;
&#xD;
               6. Smokers (refrained from any tobacco usage, including smokeless tobacco, nicotine&#xD;
                  patches, etc., for 6 months prior to the administration of the study medication.&#xD;
&#xD;
               7. History of alcohol dependence or drug abuse in the last 5 years or daily&#xD;
                  consumption of alcohol &gt; 40 g for men or 24 gr/day for women or high consumption&#xD;
                  of stimulating beverages (&gt; 5 coffees, teas or coca cola drinks/ day) for both&#xD;
                  sexes.&#xD;
&#xD;
               8. Abnormal physical findings of clinical significance at the screening examination&#xD;
                  or baseline which would interfere with the objectives of the study.&#xD;
&#xD;
               9. Need of any prescription medication within 14 days prior to the administration of&#xD;
                  the drug and non prescription medication or herbal medicines within 7 days prior&#xD;
                  to the administration of the drug.&#xD;
&#xD;
              10. Participation in other clinical trials during the previous 90 days in which an&#xD;
                  investigational drug or a commercially available drug was tested.&#xD;
&#xD;
              11. Having donated blood during 4 weeks period before inclusion in the study.&#xD;
&#xD;
              12. Existence of any surgical or medical condition which might interfere with the&#xD;
                  absortion, distribution, metabolism or excretion of the drug, i.e. impaired renal&#xD;
                  or hepatic function, diabetes mellitus, cardiovascular abnormalities, chronic&#xD;
                  symptoms of pronounced constipation or diarrhea or conditions associated with&#xD;
                  total or partial obstruction of the urinary tract.&#xD;
&#xD;
              13. 12 lead ECG obtained at screening with PR ≥ 220 msec, QRS ≥120 msec and QTc ≥ 440&#xD;
                  msec, bradychardia (&lt;50 bpm) or clinically significant minor ST wave changes or&#xD;
                  any other abnormal changes on the screening ECG that would interfere with&#xD;
                  measurement of the QT interval.&#xD;
&#xD;
              14. Symptoms of a significant somatic or mental illness in the four week period&#xD;
                  preceding drug administration.&#xD;
&#xD;
              15. History of hepatitis HBV and / or HCV and / or positive serology results which&#xD;
                  indicate the presence of hepatitis B surface antigen and / or detectable HCV&#xD;
                  ribonucleic acid (RNA).&#xD;
&#xD;
              16. Positive results from the HIV serology.&#xD;
&#xD;
              17. Females with positive results from the pregnancy test or breast-feeding.&#xD;
&#xD;
              18. Clinically significant abnormal laboratory values (as determined by the Principal&#xD;
                  Investigator) at the screening evaluation.&#xD;
&#xD;
              19. Positive results of the drugs at screening period or the day before starting&#xD;
                  treatment period. A minimum list of 6 drugs will be screened for inclusion:&#xD;
                  Amphetamines, Cocaine, Ethanol, Opiates, Cannabinoids and Benzodiazepines&#xD;
                  (positive results may be repeated at the discretion of the Principal&#xD;
                  Investigator).&#xD;
&#xD;
              20. Known hypersensitivity to the study drug or the composition of the galenical&#xD;
                  form.&#xD;
&#xD;
              21. History of psychiatric diseases or epileptic seizures.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joan Martínez Colomer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CIM Sant Pau - IIB Sant Pau</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Palobiofarma S.L. (molecule owner)</name>
      <address>
        <city>Mataró</city>
        <state>Barcelona</state>
        <zip>08302</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIM-Sant Pau - IIB Sant Pau, HSCSP</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www.iibsantpau.cat/</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>http://www.palobiofarma.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>March 7, 2016</last_update_submitted>
  <last_update_submitted_qc>March 7, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adenosine A1 receptor antagonist</keyword>
  <keyword>adenosine receptor modulator</keyword>
  <keyword>Asthma</keyword>
  <keyword>COPD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_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/NCT02208973
org study id: IIBSP-PBF-2014-04
secondary id: 2014-000425-20
nct id: NCT02208973
lead sponsor: 
collaborator: 
has dmc: No
To assess the safety and tolerability of five doses of PBF-680 (5 mg, 10 mg, 20 mg, 40 mg and
      60mg) after repeated (8 days) single daily oral dose administration in young male and female
      healthy subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of Participants with Serious and Non-Serious Adverse Events
time frame: from day 0 to day 15
description: Vital Signs, ECG recordings, laboratory safety test and phisical examination will be performed
measure: Pharmacokinetic Profile Analysis (Plasma concentrations)
time frame: from day 1 to day 8
description: Day 1: baseline [pre-dose], [+10 min], [+20 min], [+40min], [+60min], [+ 1.5h], [+2 h], [+ 2.5 h], [+ 3 h], [+ 4h], [+8h], [+ 12h] and [+16h] post-medication;
Days 2 to 7: baseline [daily pre-dose] which corresponds at +24h of previous dose;
Day 8: baseline [daily pre-dose], [+10 min], [+20 min], [+40min], [+60min], [+1.5h], [+2 h], [+ 2.5 h], [+ 3 h], [+ 4h], [+8h], [+ 12h] and [+16h] and [+ 24h] post-daily medication (D9).
measure: Adenosine A1 receptor antagonism activity
time frame: day 1 and day 8
measure: Leeds Sleep Evaluation Questionnaire
time frame: from day 1 to day 8
arm group label: PBF-680 (5 mg)
arm group type: Experimental
description: 5 mg of PBF-680
arm group label: PBF-680 (10 mg)
arm group type: Experimental
description: 10 mg of PBF-680
arm group label: PBF-680 (20 mg)
arm group type: Experimental
description: 20 mg of PBF-680
arm group label: PBF-680 (40 mg)
arm group type: Experimental
description: 40 mg of PBF-680
arm group label: PBF-680 (60 mg)
arm group type: Experimental
description: 60 mg of PBF-680
arm group label: Placebo
arm group type: Placebo Comparator
description: Comparator to the doses of 5, 10, 20, 40 and 60 mg. ( subjects for each dose level 6 are located to active treatment and two to placebo
intervention type: Drug
intervention name: PBF-680
description: 5, 10, 20, 40 and 60 mg of PBF-680
arm group label: PBF-680 (10 mg)
arm group label: PBF-680 (20 mg)
arm group label: PBF-680 (40 mg)
arm group label: PBF-680 (5 mg)
arm group label: PBF-680 (60 mg)
intervention type: Drug
intervention name: Placebo
description: placebo for the dose of 5, 10, 20 and 40 mg of PBF-680
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Joan Martínez Colomer, MD
role: Principal Investigator
affiliation: CIM Sant Pau - IIB Sant Pau
facility: 
facility: 
country: Spain
url: http://www.iibsantpau.cat/
description: Related Info
url: http://www.palobiofarma.com/
description: Related Info
responsible party type: Sponsor
mesh term: Asthma