<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/NCT04411953</url>
  </required_header>
  <id_info>
    <org_study_id>CT-006</org_study_id>
    <secondary_id>0145FRM18</secondary_id>
    <nct_id>NCT04411953</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Two Oral Haloperidol Tablets Formulations in Healthy Subjects Under Fed Conditions</brief_title>
  <official_title>A Single Center, Single Dose, Open-label, Randomized, Two Period Crossover Pivotal Study to Determine the Bioequivalence of Two Formulations Containing Haloperidol 2 mg in Healthy Males and Females Under Fed Conditions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cycle Pharmaceuticals Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>FARMOVS Clinical Research Organisation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cycle Pharmaceuticals Ltd.</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 on this study was to determine whether the test product, Haloperidol Tablets, 2&#xD;
      mg (Cycle Pharmaceuticals Ltd), and the reference product, Haloperidol Tablets, United States&#xD;
      Pharmacopeia (USP), 2 mg (Mylan Pharmaceuticals Inc.) are bioequivalent under fed conditions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific aim was to conduct a single dose, open-label, randomized, two period crossover&#xD;
      pivotal study to determine the bioequivalence of two formulations containing haloperidol 2 mg&#xD;
      in healthy males and females under fed conditions.&#xD;
&#xD;
      A total of 32 healthy female and male volunteers (age 18 to 55 years old) were entered into&#xD;
      the study. Volunteers were determined to be free of significant medical conditions as&#xD;
      assessed by medical history, physical examination, and blood and urine tests. Volunteers were&#xD;
      randomly allocated to a treatment sequence, before administration of investigational&#xD;
      medicinal product (IMP) under fed conditions.&#xD;
&#xD;
      A wash-out period of at least 14 calendar days (minimum number of days based on half-life of&#xD;
      the analyte) between consecutive administrations of the IMP was maintained.&#xD;
&#xD;
      Blood samples were collected at at pre-dose (0 hours), at 30 minutes, at 1 hour,&#xD;
&#xD;
      1 hour 30 minutes, 2 hours, 2 hours 30 minutes, 3 hours, 3 hours 30 minutes, 4 hours, 4 hours&#xD;
      30 minutes, 5 hours, 5 hours 30 minutes, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours, 30&#xD;
      hours, 36 hours, 48 hours, 72 hours, 96 hours, 120 hours, 144 hours, 168 hours and 192 hours&#xD;
      post-dose (total: 26 samples per treatment period).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 15, 2019</start_date>
  <completion_date type="Actual">December 19, 2019</completion_date>
  <primary_completion_date type="Actual">December 19, 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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Concentration Maximum (Cmax)</measure>
    <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
    <description>The maximum observed concentration of haloperidol as measured by bioanalysis of the blood plasma is referred to as the Cmax.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Curve (0-t) (AUC(0-t))</measure>
    <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
    <description>Area under the plasma concentration versus time curve from time zero to t, where t is the time of the timepoint of the last quantifiable concentration of haloperidol in the blood plasma. The curve is constructed by plotting the concentration of haloperidol in the blood plasma against the time for each blood sample.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Curve(0-∞) (AUC(0-∞))</measure>
    <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
    <description>Area under the plasma concentration versus time curve from time zero to ∞, where ∞ is the timepoint of the last quantifiable concentration of haloperidol in the blood plasma, plus it's elimination rate constant. AUC(0-∞) = AUC(0-t) + AUC(t-∞).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Concentration (Tmax)</measure>
    <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
    <description>The timepoint at which the maximum concentration of haloperidol as measured by bioanalysis of the blood plasma is observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Elimination Rate Constant (λz)</measure>
    <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
    <description>Terminal elimination rate constant (λz) is a mathematical estimate calculated using log-linear regression of the terminal portions of a blood plasma concentration against time curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Elimination Half-life (t½)</measure>
    <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
    <description>The apparent terminal elimination half-life (t½) is defined as the time necessary for the concentration of a drug to decrease by one-half in the terminal phase.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Bioequivalence</condition>
  <arm_group>
    <arm_group_label>Reference Product (Treatment A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Test Product (Treatment B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Haloperidol Tablets, Mylan Pharmaceuticals Inc.</intervention_name>
    <description>single dose, 2 mg Haloperidol tablet</description>
    <arm_group_label>Reference Product (Treatment A)</arm_group_label>
    <other_name>Benztropine Mesylate Tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Haloperidol Tablets, Cycle Pharmaceuticals Ltd</intervention_name>
    <description>single dose, 2 mg Haloperidol tablet</description>
    <arm_group_label>Test Product (Treatment B)</arm_group_label>
    <other_name>Benztropine Mesylate Tablets</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index (BMI) between 18.5 and 30 kg/m^2 (both inclusive).&#xD;
&#xD;
          -  Body mass not less than 50 kg.&#xD;
&#xD;
          -  Medical history, vital signs, physical examination, standard 12-lead electrocardiogram&#xD;
             (ECG) and laboratory investigations must be clinically acceptable or within laboratory&#xD;
             reference ranges for the relevant laboratory tests, unless the investigator considers&#xD;
             the deviation to be irrelevant for the purpose of the study.&#xD;
&#xD;
          -  Non-smokers.&#xD;
&#xD;
          -  Females, if:&#xD;
&#xD;
          -  Not of childbearing potential, e.g., has been surgically sterilized, undergone a&#xD;
             hysterectomy, amenorrhea for ≥ 12 months and considered post-menopausal, Note: In&#xD;
             post-menopausal women, the value of the serum pregnancy test may be slightly&#xD;
             increased. This test will be repeated to confirm the results. If there is no increase&#xD;
             indicative of pregnancy, the female will be included in the study.&#xD;
&#xD;
          -  Of childbearing potential, the following conditions are to be met:&#xD;
&#xD;
          -  Negative pregnancy test If this test is positive, the subject will be excluded from&#xD;
             the study. In the rare circumstance that a pregnancy is discovered after the subject&#xD;
             received IMP, every attempt must be made to follow her to term.&#xD;
&#xD;
          -  Not lactating&#xD;
&#xD;
          -  Abstaining from sexual activity (if this is the usual lifestyle of the subject) or&#xD;
             must agree to use an accepted method of contraception, and agree to continue with the&#xD;
             same method throughout the study An example of a reliable method of contraception is a&#xD;
             non-hormonal intrauterine device. In this study the concomitant use of hormonal&#xD;
             contraceptives is NOT allowed. Other methods, if considered by the investigator as&#xD;
             reliable, will be accepted.&#xD;
&#xD;
          -  Written consent given for participation in the study.&#xD;
&#xD;
          -  Written consent given for participation in the genetic component of the study (if&#xD;
             performed based on Food and Drug Administration (FDA) feedback). If the subject&#xD;
             declines participation in the genetic component, the subject will not be allowed to&#xD;
             participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional&#xD;
             or intellectual problems likely to limit the validity of consent to participate in the&#xD;
             study or limit the ability to comply with protocol requirements.&#xD;
&#xD;
          -  Current alcohol use &gt; 21 units of alcohol per week for males and &gt; 14 units of alcohol&#xD;
             per week for females (1 unit is equal to approximately 330 mL of beer, one small glass&#xD;
             [200 mL] of wine, or one measure [25 mL] of spirits).&#xD;
&#xD;
          -  Regular exposure to substances of abuse (other than alcohol) within the past year.&#xD;
&#xD;
          -  Use of any medication, prescribed or over-the-counter or herbal remedies, within 2&#xD;
             weeks before the first administration of IMP except if this will not affect the&#xD;
             outcome of the study in the opinion of the investigator. In this study the concomitant&#xD;
             use of hormonal contraceptives is NOT allowed.&#xD;
&#xD;
          -  Participation in another study with an experimental drug, where the last&#xD;
             administration of the previous IMP was within 8 weeks (or within 5 elimination&#xD;
             half-lives for chemical entities or 2 elimination half-lives for antibodies or&#xD;
             insulin, whichever is the longer) before administration of IMP in this study, at the&#xD;
             discretion of the investigator.&#xD;
&#xD;
          -  Treatment within the previous 3 months before the first administration of IMP with any&#xD;
             drug with a well-defined potential for adversely affecting a major organ or system.&#xD;
&#xD;
          -  A major illness during the 3 months before commencement of the screening period.&#xD;
&#xD;
          -  History of hypersensitivity or allergy to the IMP or its excipients or any related&#xD;
             medication.&#xD;
&#xD;
          -  History of hypersensitivity or allergy to the pre-medication or its excipients or any&#xD;
             related medication.&#xD;
&#xD;
          -  History of hypersensitivity or allergy to the rescue medication or its excipients or&#xD;
             any related medication.&#xD;
&#xD;
          -  History of bronchial asthma or any other bronchospastic disease.&#xD;
&#xD;
          -  History of convulsions.&#xD;
&#xD;
          -  History of porphyria.&#xD;
&#xD;
          -  History of cardiac arrhythmias.&#xD;
&#xD;
          -  History of sudden cardiac death in the family or history of familial long QT syndrome.&#xD;
&#xD;
          -  Relevant history or laboratory or clinical findings indicative of acute or chronic&#xD;
             disease, likely to influence study outcome.&#xD;
&#xD;
          -  Cytochrome P450 (CYP) 2D6 poor metabolizers (if warranted by the FDA).&#xD;
&#xD;
          -  Hypomagnesemia.&#xD;
&#xD;
          -  Hypothyroidism or hyperthyroidism.&#xD;
&#xD;
          -  Hypokalemia.&#xD;
&#xD;
          -  Subjects with narrow-angle glaucoma.&#xD;
&#xD;
          -  Subjects with stenosing peptic ulcers.&#xD;
&#xD;
          -  Subjects who have pyloroduodenal obstruction.&#xD;
&#xD;
          -  Subjects who have symptomatic prostatic hypertrophy or bladder-neck obstruction.&#xD;
&#xD;
          -  Known or previous dystonia or dyskinesia.&#xD;
&#xD;
          -  Subjects with severe toxic central nervous system depression or who have experienced&#xD;
             comatose states from any cause.&#xD;
&#xD;
          -  Subjects who have Parkinson's disease.&#xD;
&#xD;
          -  Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the&#xD;
             first administration of IMP.&#xD;
&#xD;
          -  Diagnosis of hypotension made during the screening period.&#xD;
&#xD;
          -  Diagnosis of hypertension made during the screening period or current diagnosis of&#xD;
             hypertension.&#xD;
&#xD;
          -  Resting pulse of &gt; 100 beats per minute or &lt; 40 beats per minute during the screening&#xD;
             period, either supine or standing.&#xD;
&#xD;
          -  Positive testing for human immunodeficiency virus (HIV), hepatitis B and hepatitis C.&#xD;
&#xD;
          -  Positive urine screen for drugs of abuse. In case of a positive result the urine&#xD;
             screen for drugs of abuse may be repeated once at the discretion of the investigator.&#xD;
&#xD;
          -  Positive pregnancy test (female subjects).&#xD;
&#xD;
          -  Hemoglobin count deviating more than 10% of the lower limit of normal.&#xD;
&#xD;
          -  Veins unsuitable for venous blood collection.&#xD;
&#xD;
          -  Difficulty in swallowing.&#xD;
&#xD;
          -  Any specific IMP safety concern.&#xD;
&#xD;
          -  Vulnerable subjects, e.g., persons in detention.&#xD;
&#xD;
          -  Employees or close relatives of the contract research organization, the sponsor, 3rd&#xD;
             party vendors or affiliates of the above mentioned parties.&#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>FARMOVS Clinical Research Organisation</name>
      <address>
        <city>Bloemfontein</city>
        <state>Free State</state>
        <zip>9301</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <results_first_submitted>January 20, 2022</results_first_submitted>
  <results_first_submitted_qc>March 9, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 8, 2022</results_first_posted>
  <last_update_submitted>March 9, 2022</last_update_submitted>
  <last_update_submitted_qc>March 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2022</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>Malnutrition</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Haloperidol</mesh_term>
    <mesh_term>Benztropine</mesh_term>
    <mesh_term>Haloperidol decanoate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT04411953/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 9, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT04411953/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>60 subjects participated in the screening phase of this study.</recruitment_details>
      <pre_assignment_details>32 subjects were enrolled in the study. 24 subjects were excluded from the study. 3 subjects were placed on standby.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Reference Product (Treatment A), Then Test Product (Treatment B)</title>
          <description>Treatment A: Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, United States Pharmacopeia (USP) (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with Investigational Medicinal Product (IMP) and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet&#xD;
Then&#xD;
Treatment B:</description>
        </group>
        <group group_id="P2">
          <title>Test Product (Treatment B), Then Reference Product (Treatment A)</title>
          <description>Treatment B: Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet&#xD;
Then&#xD;
Treatment A: Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period 1 (8 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period (14 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treatment Period 2 (8 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sequence AB</title>
          <description>Treatment A: Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet&#xD;
Treatment B: Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet</description>
        </group>
        <group group_id="B2">
          <title>Sequence BA</title>
          <description>Treatment B: Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet&#xD;
Treatment A: Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.3" spread="9.64"/>
                    <measurement group_id="B2" value="26.2" spread="6.30"/>
                    <measurement group_id="B3" value="27.3" spread="8.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>South Africa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="170.53" spread="8.586"/>
                    <measurement group_id="B2" value="168.64" spread="8.380"/>
                    <measurement group_id="B3" value="169.59" spread="8.401"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.69" spread="12.121"/>
                    <measurement group_id="B2" value="65.63" spread="10.036"/>
                    <measurement group_id="B3" value="67.66" spread="11.139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.90" spread="3.300"/>
                    <measurement group_id="B2" value="23.03" spread="2.763"/>
                    <measurement group_id="B3" value="23.47" spread="3.026"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Concentration Maximum (Cmax)</title>
        <description>The maximum observed concentration of haloperidol as measured by bioanalysis of the blood plasma is referred to as the Cmax.</description>
        <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
        <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Reference Product (Treatment A)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet</description>
          </group>
          <group group_id="O2">
            <title>Test Product (Treatment B)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration Maximum (Cmax)</title>
          <description>The maximum observed concentration of haloperidol as measured by bioanalysis of the blood plasma is referred to as the Cmax.</description>
          <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.326" spread="0.4338"/>
                    <measurement group_id="O2" value="1.293" spread="0.3919"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Curve (0-t) (AUC(0-t))</title>
        <description>Area under the plasma concentration versus time curve from time zero to t, where t is the time of the timepoint of the last quantifiable concentration of haloperidol in the blood plasma. The curve is constructed by plotting the concentration of haloperidol in the blood plasma against the time for each blood sample.</description>
        <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
        <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Reference Product (Treatment A)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet</description>
          </group>
          <group group_id="O2">
            <title>Test Product (Treatment B)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve (0-t) (AUC(0-t))</title>
          <description>Area under the plasma concentration versus time curve from time zero to t, where t is the time of the timepoint of the last quantifiable concentration of haloperidol in the blood plasma. The curve is constructed by plotting the concentration of haloperidol in the blood plasma against the time for each blood sample.</description>
          <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
          <units>h*ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.75" spread="10.19"/>
                    <measurement group_id="O2" value="28.46" spread="11.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Curve(0-∞) (AUC(0-∞))</title>
        <description>Area under the plasma concentration versus time curve from time zero to ∞, where ∞ is the timepoint of the last quantifiable concentration of haloperidol in the blood plasma, plus it's elimination rate constant. AUC(0-∞) = AUC(0-t) + AUC(t-∞).</description>
        <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
        <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Reference Product (Treatment A)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet</description>
          </group>
          <group group_id="O2">
            <title>Test Product (Treatment B)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve(0-∞) (AUC(0-∞))</title>
          <description>Area under the plasma concentration versus time curve from time zero to ∞, where ∞ is the timepoint of the last quantifiable concentration of haloperidol in the blood plasma, plus it's elimination rate constant. AUC(0-∞) = AUC(0-t) + AUC(t-∞).</description>
          <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
          <units>h*ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.61" spread="11.29"/>
                    <measurement group_id="O2" value="31.34" spread="12.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Concentration (Tmax)</title>
        <description>The timepoint at which the maximum concentration of haloperidol as measured by bioanalysis of the blood plasma is observed.</description>
        <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
        <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Reference Product (Treatment A)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet</description>
          </group>
          <group group_id="O2">
            <title>Test Product (Treatment B)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Concentration (Tmax)</title>
          <description>The timepoint at which the maximum concentration of haloperidol as measured by bioanalysis of the blood plasma is observed.</description>
          <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
          <units>Hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.871" spread="3.750"/>
                    <measurement group_id="O2" value="3.839" spread="1.274"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Elimination Rate Constant (λz)</title>
        <description>Terminal elimination rate constant (λz) is a mathematical estimate calculated using log-linear regression of the terminal portions of a blood plasma concentration against time curve.</description>
        <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
        <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Reference Product (Treatment A)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet</description>
          </group>
          <group group_id="O2">
            <title>Test Product (Treatment B)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Elimination Rate Constant (λz)</title>
          <description>Terminal elimination rate constant (λz) is a mathematical estimate calculated using log-linear regression of the terminal portions of a blood plasma concentration against time curve.</description>
          <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
          <units>1/h</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01114" spread="0.003451"/>
                    <measurement group_id="O2" value="0.01152" spread="0.004028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Elimination Half-life (t½)</title>
        <description>The apparent terminal elimination half-life (t½) is defined as the time necessary for the concentration of a drug to decrease by one-half in the terminal phase.</description>
        <time_frame>pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose</time_frame>
        <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Reference Product (Treatment A)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet</description>
          </group>
          <group group_id="O2">
            <title>Test Product (Treatment B)</title>
            <description>Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Elimination Half-life (t½)</title>
          <description>The apparent terminal elimination half-life (t½) is defined as the time necessary for the concentration of a drug to decrease by one-half in the terminal phase.</description>
          <population>One subject was withdrawn after the interim safety analysis during the washout period and so did not complete Treatment Period 2 (the subject was scheduled to receive Test Product (Treatment B)). Since only 31 subjects completed the study, only 31 subjects were included in the statistical analysis.</population>
          <units>Hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.12" spread="26.40"/>
                    <measurement group_id="O2" value="70.19" spread="35.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events data was collected for the duration of the study (24 days).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Reference Product (Treatment A)</title>
          <description>Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Mylan Pharmaceuticals Inc.: single dose, 2 mg Haloperidol tablet</description>
        </group>
        <group group_id="E2">
          <title>Test Product (Treatment B)</title>
          <description>Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.&#xD;
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.&#xD;
Haloperidol Tablets, Cycle Pharmaceuticals Ltd: single dose, 2 mg Haloperidol tablet</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Eye Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="31"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Aphthous Ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Skin Laceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Costochondritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Spinal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hypervigilance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Throat</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="31"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Nasal Dryness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Throat Irritation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Upper-airway Cough Syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Global Regulatory Affairs and Clinical Development</name_or_title>
      <organization>Cycle Pharmaceuticals</organization>
      <phone>+441223803635</phone>
      <email>claudia.percivalle@cyclepharma.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04411953
org study id: CT-006
secondary id: 0145FRM18
nct id: NCT04411953
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose on this study was to determine whether the test product, Haloperidol Tablets, 2
      mg (Cycle Pharmaceuticals Ltd), and the reference product, Haloperidol Tablets, United States
      Pharmacopeia (USP), 2 mg (Mylan Pharmaceuticals Inc.) are bioequivalent under fed conditions.
The specific aim was to conduct a single dose, open-label, randomized, two period crossover
      pivotal study to determine the bioequivalence of two formulations containing haloperidol 2 mg
      in healthy males and females under fed conditions.

      A total of 32 healthy female and male volunteers (age 18 to 55 years old) were entered into
      the study. Volunteers were determined to be free of significant medical conditions as
      assessed by medical history, physical examination, and blood and urine tests. Volunteers were
      randomly allocated to a treatment sequence, before administration of investigational
      medicinal product (IMP) under fed conditions.

      A wash-out period of at least 14 calendar days (minimum number of days based on half-life of
      the analyte) between consecutive administrations of the IMP was maintained.

      Blood samples were collected at at pre-dose (0 hours), at 30 minutes, at 1 hour,

      1 hour 30 minutes, 2 hours, 2 hours 30 minutes, 3 hours, 3 hours 30 minutes, 4 hours, 4 hours
      30 minutes, 5 hours, 5 hours 30 minutes, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours, 30
      hours, 36 hours, 48 hours, 72 hours, 96 hours, 120 hours, 144 hours, 168 hours and 192 hours
      post-dose (total: 26 samples per treatment period).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Concentration Maximum (Cmax)
time frame: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose
description: The maximum observed concentration of haloperidol as measured by bioanalysis of the blood plasma is referred to as the Cmax.
measure: Area Under the Curve (0-t) (AUC(0-t))
time frame: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose
description: Area under the plasma concentration versus time curve from time zero to t, where t is the time of the timepoint of the last quantifiable concentration of haloperidol in the blood plasma. The curve is constructed by plotting the concentration of haloperidol in the blood plasma against the time for each blood sample.
measure: Area Under the Curve(0-∞) (AUC(0-∞))
time frame: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose
description: Area under the plasma concentration versus time curve from time zero to ∞, where ∞ is the timepoint of the last quantifiable concentration of haloperidol in the blood plasma, plus it's elimination rate constant. AUC(0-∞) = AUC(0-t) + AUC(t-∞).
measure: Time to Maximum Concentration (Tmax)
time frame: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose
description: The timepoint at which the maximum concentration of haloperidol as measured by bioanalysis of the blood plasma is observed.
measure: Terminal Elimination Rate Constant (λz)
time frame: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose
description: Terminal elimination rate constant (λz) is a mathematical estimate calculated using log-linear regression of the terminal portions of a blood plasma concentration against time curve.
measure: Terminal Elimination Half-life (t½)
time frame: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose
description: The apparent terminal elimination half-life (t½) is defined as the time necessary for the concentration of a drug to decrease by one-half in the terminal phase.
arm group label: Reference Product (Treatment A)
arm group type: Active Comparator
description: Subjects received Haloperidol Tablets 2 mg Reference Product (Mylan Pharmaceuticals Inc.). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.
arm group label: Test Product (Treatment B)
arm group type: Experimental
description: Subjects received Haloperidol Tablets 2 mg Test Product (Cycle Pharmaceuticals Ltd). Subjects also received as pre-medication Benztropine Mesylate Tablets, USP (1 mg every 10 to 12 hours), beginning 4 to 6 hours before dosing with IMP and continued for a total of 4 doses.
A high-fat, high-calorie breakfast was served 30 minute before administration of the IMP.
intervention type: Drug
intervention name: Haloperidol Tablets, Mylan Pharmaceuticals Inc.
description: single dose, 2 mg Haloperidol tablet
arm group label: Reference Product (Treatment A)
other name: Benztropine Mesylate Tablets
intervention type: Drug
intervention name: Haloperidol Tablets, Cycle Pharmaceuticals Ltd
description: single dose, 2 mg Haloperidol tablet
arm group label: Test Product (Treatment B)
other name: Benztropine Mesylate Tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: South Africa
responsible party type: Sponsor
mesh term: Malnutrition
mesh term: Haloperidol
mesh term: Benztropine
mesh term: Haloperidol decanoate
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 