<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/NCT04478357</url>
  </required_header>
  <id_info>
    <org_study_id>A0221106</org_study_id>
    <secondary_id>2014-002783-32</secondary_id>
    <nct_id>NCT04478357</nct_id>
  </id_info>
  <brief_title>BIOEQUIVALENCE STUDY IN HEALTHY PARTICIPANTS COMPARING 4 MG AND 8 MG FESOTERODINE EXTENDED-RELEASE TABLETS (TOVIAZ™), MANUFACTURED AT ZWICKAU VERSUS FREIBURG</brief_title>
  <official_title>AN OPEN-LABEL, RANDOMIZED, SINGLE-DOSE, 4 PERIOD, 4 TREATMENT, 2 SEQUENCE, TWO 2 WAY CROSSOVER, BIOEQUIVALENCE STUDY IN HEALTHY PARTICIPANTS COMPARING 4 MG AND 8 MG FESOTERODINE EXTENDED RELEASE TABLETS (TOVIAZ(TM)), MANUFACTURED AT ZWICKAU VERSUS FREIBURG</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Fesoterodine (Toviaz™) extended-release (ER) tablets are currently manufactured by Aesica&#xD;
      Pharmaceuticals, Zwickau, Germany (Zwickau). An additional manufacturing location at Pfizer&#xD;
      Freiburg, Germany (Freiburg) has been identified. This pivotal bioequivalence (BE) study is&#xD;
      being conducted to satisfy the United States (US) Food and Drug Administration (FDA)&#xD;
      regulatory requirements for the qualification of the Freiburg manufacturing site.&#xD;
&#xD;
      Overall Study Design This is an open-label, randomized, single-dose, 4-period, 4-treatment,&#xD;
      2-sequence, two 2-way crossover study in healthy participants. This study will assess the BE&#xD;
      of Fesoterodine (Toviaz™) 4 mg and 8 mg ER tablets manufactured at Zwickau (Reference) versus&#xD;
      Freiburg (Test). Study participants will include healthy male and/or female individuals&#xD;
      between the ages of 18 and 55 years, inclusive. Approximately 18 participants who fulfill&#xD;
      entry criteria will be randomized to 1 of the 2 treatment sequences as shown in the table&#xD;
      below.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 12, 2019</start_date>
  <completion_date type="Actual">November 12, 2020</completion_date>
  <primary_completion_date type="Actual">November 12, 2020</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>
    <intervention_model_description>This is an open-label, randomized, single-dose, 4-period, 4-treatment, 2-sequence, two 2-way crossover study in healthy participants. This study will assess the BE of Fesoterodine (Toviaz™) 4 mg and 8 mg ER tablets manufactured at Zwickau (Reference) versus Freiburg (Test). Study participants will include healthy male and/or female individuals between the ages of 18 and 55 years, inclusive. Approximately 18 participants who fulfill entry criteria will be randomized to 1 of the 2 treatment sequences as shown in the table below.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours</time_frame>
    <description>Maximum Observed Plasma Concentration (Cmax) of 5-Hydroxymethyl-tolterodine (5-HMT)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCinf (if data permit, otherwise AUClast)</measure>
    <time_frame>0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours</time_frame>
    <description>Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of 5-Hydroxymethyl-tolterodine (5-HMT)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUCLast</measure>
    <time_frame>0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours</time_frame>
    <description>Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of 5-Hydroxymethyl-tolterodine (5-HMT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours</time_frame>
    <description>Time to Reach Maximum Observed Plasma Concentration (Tmax) of 5-Hydroxymethyl-tolterodine (5-HMT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2</measure>
    <time_frame>0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours</time_frame>
    <description>Plasma Decay Half-Life (t1/2) of 5-Hydroxymethyl-tolterodine (5-HMT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)</measure>
    <time_frame>Day -28 to day -1, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours, Day 28 to 35 and on early termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Change From Baseline in Vital Signs</measure>
    <time_frame>Day -28 to day -1, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours, Day 28 to 35 and on early termination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities</measure>
    <time_frame>During screening</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Neurogenic Detrusor Overactivity</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>4 mg fesoterodine ER tablet manufactured at Zwickau.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>4 mg fesoterodine ER tablet manufactured at Freiburg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>8 mg fesoterodine ER tablet manufactured at Zwickau</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment D</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>8 mg fesoterodine ER tablet manufactured at Freiburg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>4 mg Fesoterodine ER tablet from Zwickau</intervention_name>
    <description>Manufactured at Zwickau</description>
    <arm_group_label>Treatment A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>4 mg fesoterodine ER tablet from Freiburg</intervention_name>
    <description>Manufactured at Freiburg</description>
    <arm_group_label>Treatment B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>8 mg fesoterodine ER tablet from Zwickau</intervention_name>
    <description>Manufactured at Zwickau</description>
    <arm_group_label>Treatment C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>8 mg fesoterodine ER tablet from Freiburg</intervention_name>
    <description>Manufactured at Freiburg</description>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female participants must be 18 to 55 years of age, inclusive, at the time of&#xD;
             signing the informed consent document (ICD).&#xD;
&#xD;
          2. Male and female participants who are overtly healthy as determined by medical&#xD;
             evaluation including a detailed medical history, complete physical examination,&#xD;
             cardiovascular tests including blood pressure (BP), pulse rate measurement and 12-lead&#xD;
             ECG, and clinical laboratory tests.&#xD;
&#xD;
          3. Participants who are willing and able to comply with all scheduled visits, treatment&#xD;
             plan, laboratory tests, lifestyle considerations, and other study procedures.&#xD;
&#xD;
          4. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight &gt;50 kg (110 lb).&#xD;
&#xD;
          5. Capable of giving signed informed consent as described in Appendix 1, which includes&#xD;
             compliance with the requirements and restrictions listed in the informed consent&#xD;
             document (ICD) and in this protocol.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or&#xD;
             allergic disease (including drug allergies, but excluding untreated, asymptomatic,&#xD;
             seasonal allergies at the time of dosing).&#xD;
&#xD;
          2. Any condition possibly affecting drug absorption (eg, gastrectomy).&#xD;
&#xD;
          3. History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C&#xD;
             infection; positive testing for HIV, hepatitis B surface antigen (HBsAg), or hepatitis&#xD;
             C antibody (HCVAb). Hepatitis B vaccination is allowed.&#xD;
&#xD;
          4. Other acute or chronic medical or psychiatric condition including recent (within the&#xD;
             past year) or active suicidal ideation or behavior or laboratory abnormality that may&#xD;
             increase the risk associated with study participation or investigational product&#xD;
             administration or may interfere with the interpretation of study results and, in the&#xD;
             judgment of the investigator, would make the participant inappropriate for entry into&#xD;
             this study.&#xD;
&#xD;
          5. History of allergy or hypersensitivity to fesoterodine fumarate or tolterodine&#xD;
             tartrate, soya, or any of the excipients in the investigational drug product.&#xD;
&#xD;
          6. History of uncontrolled narrow angle glaucoma, myasthenia gravis, gastric retention,&#xD;
             severe ulcerative colitis and toxic megacolon.&#xD;
&#xD;
          7. Evidence or history of clinically significant urologic disease, urinary retention,&#xD;
             obstructive disturbance of bladder emptying, micturition disturbance, nocturia or&#xD;
             pollacisuria (eg, benign prostate hyperplasia, urethral stricture, recurrent urinary&#xD;
             tract infections).&#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>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brussels Clinical Research Unit</name>
      <address>
        <city>Brussels</city>
        <state>Bruxelles-capitale, Région DE</state>
        <zip>B-1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <link>
    <url>https://pmiform.com/clinical-trial-info-request?StudyID=A0221106</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>May 6, 2021</last_update_submitted>
  <last_update_submitted_qc>May 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase I</keyword>
  <keyword>Fesoterodine beads- in-capsule</keyword>
  <keyword>bioequivalence</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Toviaz</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Bladder, Overactive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fesoterodine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
  </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/NCT04478357
org study id: A0221106
secondary id: 2014-002783-32
nct id: NCT04478357
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Fesoterodine (Toviaz™) extended-release (ER) tablets are currently manufactured by Aesica
      Pharmaceuticals, Zwickau, Germany (Zwickau). An additional manufacturing location at Pfizer
      Freiburg, Germany (Freiburg) has been identified. This pivotal bioequivalence (BE) study is
      being conducted to satisfy the United States (US) Food and Drug Administration (FDA)
      regulatory requirements for the qualification of the Freiburg manufacturing site.

      Overall Study Design This is an open-label, randomized, single-dose, 4-period, 4-treatment,
      2-sequence, two 2-way crossover study in healthy participants. This study will assess the BE
      of Fesoterodine (Toviaz™) 4 mg and 8 mg ER tablets manufactured at Zwickau (Reference) versus
      Freiburg (Test). Study participants will include healthy male and/or female individuals
      between the ages of 18 and 55 years, inclusive. Approximately 18 participants who fulfill
      entry criteria will be randomized to 1 of the 2 treatment sequences as shown in the table
      below.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This is an open-label, randomized, single-dose, 4-period, 4-treatment, 2-sequence, two 2-way crossover study in healthy participants. This study will assess the BE of Fesoterodine (Toviaz™) 4 mg and 8 mg ER tablets manufactured at Zwickau (Reference) versus Freiburg (Test). Study participants will include healthy male and/or female individuals between the ages of 18 and 55 years, inclusive. Approximately 18 participants who fulfill entry criteria will be randomized to 1 of the 2 treatment sequences as shown in the table below.
primary purpose: Other
masking: None (Open Label)
measure: Cmax
time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
description: Maximum Observed Plasma Concentration (Cmax) of 5-Hydroxymethyl-tolterodine (5-HMT)
measure: AUCinf (if data permit, otherwise AUClast)
time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
description: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of 5-Hydroxymethyl-tolterodine (5-HMT)
measure: AUCLast
time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
description: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of 5-Hydroxymethyl-tolterodine (5-HMT)
measure: Tmax
time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
description: Time to Reach Maximum Observed Plasma Concentration (Tmax) of 5-Hydroxymethyl-tolterodine (5-HMT)
measure: t1/2
time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours
description: Plasma Decay Half-Life (t1/2) of 5-Hydroxymethyl-tolterodine (5-HMT)
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
time frame: Day -28 to day -1, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours, Day 28 to 35 and on early termination
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
time frame: Day -28 to day -1, 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 30, 36, and 48 hours, Day 28 to 35 and on early termination
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities
time frame: During screening
arm group label: Treatment A
arm group type: Other
description: 4 mg fesoterodine ER tablet manufactured at Zwickau.
arm group label: Treatment B
arm group type: Other
description: 4 mg fesoterodine ER tablet manufactured at Freiburg
arm group label: Treatment C
arm group type: Other
description: 8 mg fesoterodine ER tablet manufactured at Zwickau
arm group label: Treatment D
arm group type: Other
description: 8 mg fesoterodine ER tablet manufactured at Freiburg.
intervention type: Drug
intervention name: 4 mg Fesoterodine ER tablet from Zwickau
description: Manufactured at Zwickau
arm group label: Treatment A
intervention type: Drug
intervention name: 4 mg fesoterodine ER tablet from Freiburg
description: Manufactured at Freiburg
arm group label: Treatment B
intervention type: Drug
intervention name: 8 mg fesoterodine ER tablet from Zwickau
description: Manufactured at Zwickau
arm group label: Treatment C
intervention type: Drug
intervention name: 8 mg fesoterodine ER tablet from Freiburg
description: Manufactured at Freiburg
arm group label: Treatment D
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: Belgium
url: https://pmiform.com/clinical-trial-info-request?StudyID=A0221106
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Urinary Bladder, Overactive
mesh term: Fesoterodine
sharing ipd: No
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.