<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/NCT03820037</url>
  </required_header>
  <id_info>
    <org_study_id>BIA-91067-132</org_study_id>
    <nct_id>NCT03820037</nct_id>
  </id_info>
  <brief_title>Relative Bioavailability and Bioequivalence of Opicapone</brief_title>
  <official_title>A Phase I, Open-Label, Randomised, Three-Period, Three-Sequence, Partial Replicate Crossover Study to Investigate the Relative Bioavailability and Bioequivalence of Opicapone Obtained From Two Different Sources, Under Fasting Conditions After Single-dose Administration in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bial - Portela C S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bial - Portela C S.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      the purpose assess the relative bioavailability and bioequivalence of two active&#xD;
      pharmaceutical ingredient (API) sources of opicapone (OPC, Ongentys® and BIA 9-1067)&#xD;
      following single 50 mg dose administration under fasting conditions in healthy volunteers&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a Phase I, open label, randomized, partial-replicate, three-period,&#xD;
      three-sequence crossover study to investigate the relative bioavailability and bioequivalence&#xD;
      of 2 API sources of OPC (BIA 9-1067 [Test] and Ongentys® [Reference]) in healthy adult&#xD;
      subjects.&#xD;
&#xD;
      Subjects will be randomized in a 3-period, 3-sequence crossover design; each subject will&#xD;
      receive 2 single oral 50 mg doses of the Reference API source of OPC, and a single 50 mg dose&#xD;
      of the Test API source of OPC under fasting conditions.&#xD;
&#xD;
      Potential subjects will be screened to assess their eligibility to enter the study within 28&#xD;
      days prior to the first dose administration. Subjects will be admitted into the Clinical&#xD;
      Research Unit (CRU) on Day 1 and be confined to the CRU until discharge on Day 3. There will&#xD;
      be a washout period of at least 14 days between each dose. A follow-up visit will be&#xD;
      performed 7 to 14 days after dosing in the last treatment period or early discontinuation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 19, 2019</start_date>
  <completion_date type="Actual">June 9, 2019</completion_date>
  <primary_completion_date type="Actual">June 9, 2019</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>area under the plasma concentration-time curve from time zero to infinity (AUC0 ∞)</measure>
    <time_frame>Day 1 up to day 14</time_frame>
    <description>PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>area under the plasma concentration-time curve from time zero to the last observable concentration at time t (AUC0 t)</measure>
    <time_frame>Day 1 up to day 14</time_frame>
    <description>PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>maximum observed plasma concentration (Cmax)</measure>
    <time_frame>Day 1 up to day 14</time_frame>
    <description>PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>OPC, Ongentys</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single oral doses of 50 mg opicapone, administered using the reference (Ongentys ®) active pharmaceutical ingredient (API) source</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BIA 9-1067</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single oral doses of 50 mg opicapone, administered using the test (BIA 9-1067)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ongentys</intervention_name>
    <description>single oral 50 mg (capsule containing 50 mg OPC) under fasting conditions</description>
    <arm_group_label>OPC, Ongentys</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIA 9-1067 (test)</intervention_name>
    <description>single oral 50 mg (capsule containing 50 mg OPC) under fasting conditions</description>
    <arm_group_label>BIA 9-1067</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females, between 18 and 55 years of age, inclusive.&#xD;
&#xD;
          2. Body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive.&#xD;
&#xD;
          3. Healthy subjects as determined by no clinically significant findings from medical&#xD;
             history, physical examination, complete neurological examination, 12 lead ECG, vital&#xD;
             signs measurements, and clinical laboratory evaluations (congenital nonhaemolytic&#xD;
             hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct&#xD;
             bilirubin] is not acceptable) at Screening and Check in as assessed by the&#xD;
             Investigator (or designee).&#xD;
&#xD;
          4. Females will not be pregnant (i.e. the the pregnancy test at screening and at&#xD;
             admission to each treatment period must be negative), or lactating, and females of&#xD;
             childbearing potential and males will agree to use contraception.&#xD;
&#xD;
          5. Able to comprehend and willing to sign and date an Informed Consent Form (ICF) before&#xD;
             any study-specific screening procedure is performed, and to abide by the study&#xD;
             restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Significant history or clinical manifestation of any metabolic, allergic,&#xD;
             dermatological, hepatic, renal, haematological, lymphatic, cardiovascular,&#xD;
             gastrointestinal, neurological, respiratory, endocrine, genitourinary, immunological,&#xD;
             connective tissue diseases or disorders, musculoskeletal, psychiatric disorder, or&#xD;
             have a clinically relevant surgical history as determined by the Investigator (or&#xD;
             designee).&#xD;
&#xD;
          2. History of significant hypersensitivity, intolerance, or allergy to any drug compound,&#xD;
             food, or other substance, unless approved by the Investigator (or designee).&#xD;
&#xD;
          3. History of febrile illness within 10 days prior to the each dose of study drug, or&#xD;
             subjects with evidence of active infection&#xD;
&#xD;
          4. Acute gastrointestinal symptoms (eg nausea, vomiting, diarrhoea, heartburn) as&#xD;
             determined by the Investigator (or designee).&#xD;
&#xD;
          5. Significantly impaired hepatic function, defined as any of the following (confirmed by&#xD;
             repeat):&#xD;
&#xD;
               1. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) &gt; 1.5 x&#xD;
                  upper limit of normal (ULN)&#xD;
&#xD;
               2. Total bilirubin (TBL) &gt; 2 x ULN&#xD;
&#xD;
          6. Significant personal or family history of haemostatic disorders&#xD;
&#xD;
          7. History of galactose intolerance (eg the Lapp lactase deficiency or glucose-galactose&#xD;
             malabsorption)&#xD;
&#xD;
          8. Symptomatic orthostatic hypotension (drop of &gt; 20 mmHg in systolic blood pressure&#xD;
             and/or &gt; 10 mmHg in diastolic blood pressure) when moving from supine to standing&#xD;
             position, together with other symptoms, e.g., dizziness.&#xD;
&#xD;
          9. History of stomach or intestinal surgery or resection that would potentially alter&#xD;
             absorption and/or excretion of orally administered drugs (uncomplicated appendectomy&#xD;
             and hernia repair will be allowed).&#xD;
&#xD;
         10. History of alcoholism or drug/chemical abuse within 2 years prior to Check in to the&#xD;
             first treatment period.&#xD;
&#xD;
         11. Alcohol consumption of &gt;21 units per week for males and &gt;14 units for females. One&#xD;
             unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or&#xD;
             1/6 gill (25 mL) of spirits.&#xD;
&#xD;
         12. Positive alcohol breath test result or positive urine drug screen (confirmed by&#xD;
             repeat) at Screening or Check in to each treatment period.&#xD;
&#xD;
         13. Positive hepatitis panel and/or positive human immunodeficiency virus test&#xD;
&#xD;
         14. Participation in a clinical study involving administration of an investigational drug&#xD;
             (new chemical entity) in the past 90 days prior to first dose of study drug.&#xD;
&#xD;
         15. Use or intend to use any medications/products known to alter drug absorption,&#xD;
             metabolism, or elimination processes, including St. John's wort, within 30 days prior&#xD;
             to Check-in of the first treatment period, unless deemed acceptable by the&#xD;
             Investigator (or designee).&#xD;
&#xD;
         16. Use or intend to use any prescription medications/products within 14 days prior to&#xD;
             dosing, unless deemed acceptable by the Investigator (or designee).&#xD;
&#xD;
         17. Use or intend to use slow release medications/products considered to still be active&#xD;
             within 14 days prior to Check in, unless deemed acceptable by the Investigator (or&#xD;
             designee).&#xD;
&#xD;
         18. Use or intend to use any nonprescription medications/products including vitamins,&#xD;
             minerals, and phytotherapeutic/herbal/plant derived preparations within 7 days prior&#xD;
             to Check in, unless deemed acceptable by the Investigator (or designee).&#xD;
&#xD;
         19. Use of tobacco or nicotine containing products within 3 months prior to Check in, or&#xD;
             positive cotinine at Screening or Check-in.&#xD;
&#xD;
         20. Receipt of blood products within 2 months prior to Check in.&#xD;
&#xD;
         21. Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to&#xD;
             Screening, or platelets from 6 weeks prior to Screening.&#xD;
&#xD;
         22. Subjects who are vegetarians, vegans or have medical dietary restrictions&#xD;
&#xD;
         23. Poor peripheral venous access.&#xD;
&#xD;
         24. Have previously completed or withdrawn from this study or any other study&#xD;
             investigating opicapone, and have previously received the investigational product.&#xD;
&#xD;
         25. Subjects who, in the opinion of the Investigator (or designee), should not participate&#xD;
             in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Covance Clinical Research</name>
      <address>
        <city>Leeds</city>
        <zip>LS2 9LH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>December 30, 2020</last_update_submitted>
  <last_update_submitted_qc>December 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opicapone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03820037
org study id: BIA-91067-132
nct id: NCT03820037
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
the purpose assess the relative bioavailability and bioequivalence of two active
      pharmaceutical ingredient (API) sources of opicapone (OPC, Ongentys® and BIA 9-1067)
      following single 50 mg dose administration under fasting conditions in healthy volunteers
This will be a Phase I, open label, randomized, partial-replicate, three-period,
      three-sequence crossover study to investigate the relative bioavailability and bioequivalence
      of 2 API sources of OPC (BIA 9-1067 [Test] and Ongentys® [Reference]) in healthy adult
      subjects.

      Subjects will be randomized in a 3-period, 3-sequence crossover design; each subject will
      receive 2 single oral 50 mg doses of the Reference API source of OPC, and a single 50 mg dose
      of the Test API source of OPC under fasting conditions.

      Potential subjects will be screened to assess their eligibility to enter the study within 28
      days prior to the first dose administration. Subjects will be admitted into the Clinical
      Research Unit (CRU) on Day 1 and be confined to the CRU until discharge on Day 3. There will
      be a washout period of at least 14 days between each dose. A follow-up visit will be
      performed 7 to 14 days after dosing in the last treatment period or early discontinuation.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: area under the plasma concentration-time curve from time zero to infinity (AUC0 ∞)
time frame: Day 1 up to day 14
description: PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.
measure: area under the plasma concentration-time curve from time zero to the last observable concentration at time t (AUC0 t)
time frame: Day 1 up to day 14
description: PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.
measure: maximum observed plasma concentration (Cmax)
time frame: Day 1 up to day 14
description: PK parameters from Blood samples to be be collected for the analysis of plasma concentrations of opicapone.
arm group label: OPC, Ongentys
arm group type: Active Comparator
description: Single oral doses of 50 mg opicapone, administered using the reference (Ongentys ®) active pharmaceutical ingredient (API) source
arm group label: BIA 9-1067
arm group type: Experimental
description: Single oral doses of 50 mg opicapone, administered using the test (BIA 9-1067)
intervention type: Drug
intervention name: Ongentys
description: single oral 50 mg (capsule containing 50 mg OPC) under fasting conditions
arm group label: OPC, Ongentys
intervention type: Drug
intervention name: BIA 9-1067 (test)
description: single oral 50 mg (capsule containing 50 mg OPC) under fasting conditions
arm group label: BIA 9-1067
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Opicapone
sharing ipd: Undecided