Bioequivalence Study of Two Oral Haloperidol Tablets Formulations in Healthy Subjects Under Fasting Conditions
Condition: Bioequivalence
Intervention: Haloperidol Tablets, Mylan Pharmaceuticals Inc.; Haloperidol Tablets, Cycle Pharmaceuticals Ltd
Intervention description: single dose, 2 mg Haloperidol tablet; single dose, 2 mg Haloperidol tablet
Intervention MeSH terms: Haloperidol; Benztropine; Haloperidol decanoate
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Crossover Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body mass index (BMI) between 18.5 and 30 kg/m^2 (both inclusive).

          -  Body mass not less than 50 kg.

          -  Medical history, vital signs, physical examination, standard 12-lead electrocardiogram
             (ECG) and laboratory investigations must be clinically acceptable or within laboratory
             reference ranges for the relevant laboratory tests, unless the investigator considers
             the deviation to be irrelevant for the purpose of the study.

          -  Non-smokers.

          -  Females, if:

               -  Not of childbearing potential, e.g., has been surgically sterilized, undergone a
                  hysterectomy, amenorrhea for ≥ 12 months and considered post-menopausal, Note: In
                  post-menopausal women, the value of the serum pregnancy test may be slightly
                  increased. This test will be repeated to confirm the results. If there is no
                  increase indicative of pregnancy, the female will be included in the study.

               -  Of childbearing potential, the following conditions are to be met:

          -  Negative pregnancy test If this test is positive, the subject will be excluded from
             the study. In the rare circumstance that a pregnancy is discovered after the subject
             received IMP, every attempt must be made to follow her to term.

          -  Not lactating

          -  Abstaining from sexual activity (if this is the usual lifestyle of the subject) or
             must agree to use an accepted method of contraception, and agree to continue with the
             same method throughout the study An example of a reliable method of contraception is a
             non-hormonal intrauterine device. In this study the concomitant use of hormonal
             contraceptives is NOT allowed. Other methods, if considered by the investigator as
             reliable, will be accepted.

          -  Written consent given for participation in the study.

          -  Written consent given for participation in the genetic component of the study (if
             performed based on Food and Drug Administration (FDA) feedback). If the subject
             declines participation in the genetic component, the subject will not be allowed to
             participate in the study.

        Exclusion Criteria:

          -  Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional
             or intellectual problems likely to limit the validity of consent to participate in the
             study or limit the ability to comply with protocol requirements.

          -  Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol
             per week for females (1 unit is equal to approximately 330 mL of beer, one small glass
             [200 mL] of wine, or one measure [25 mL] of spirits).

          -  Regular exposure to substances of abuse (other than alcohol) within the past year.

          -  Use of any medication, prescribed or over-the-counter or herbal remedies, within 2
             weeks before the first administration of IMP except if this will not affect the
             outcome of the study in the opinion of the investigator. In this study the concomitant
             use of hormonal contraceptives is NOT allowed.

          -  Participation in another study with an experimental drug, where the last
             administration of the previous IMP was within 8 weeks (or within 5 elimination
             half-lives for chemical entities or 2 elimination half-lives for antibodies or
             insulin, whichever is the longer) before administration of IP in this study, at the
             discretion of the investigator.

          -  Treatment within the previous 3 months before the first administration of IMP with any
             drug with a well-defined potential for adversely affecting a major organ or system.

          -  A major illness during the 3 months before commencement of the screening period.

          -  History of hypersensitivity or allergy to the IMP or its excipients or any related
             medication.

          -  History of hypersensitivity or allergy to the pre-medication or its excipients or any
             related medication.

          -  History of hypersensitivity or allergy to the rescue medication or its excipients or
             any related medication.

          -  History of bronchial asthma or any other bronchospastic disease.

          -  History of convulsions.

          -  History of porphyria.

          -  History of cardiac arrhythmias.

          -  History of sudden cardiac death in the family or history of familial long QT syndrome.

          -  Relevant history or laboratory or clinical findings indicative of acute or chronic
             disease, likely to influence study outcome.

          -  Cytochrome P450 (CYP) 2D6 poor metabolizers (if warranted by the FDA).

          -  Hypomagnesemia.

          -  Hypothyroidism or hyperthyroidism.

          -  Hypokalemia.

          -  Subjects with narrow-angle glaucoma.

          -  Subjects with stenosing peptic ulcers.

          -  Subjects who have pyloroduodenal obstruction.

          -  Subjects who have symptomatic prostatic hypertrophy or bladder-neck obstruction.

          -  Known or previous dystonia or dyskinesia.

          -  Subjects with severe toxic central nervous system depression or who have experienced
             comatose states from any cause.

          -  Subjects who have Parkinson's disease.

          -  Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the
             first administration of IMP.

          -  Diagnosis of hypotension made during the screening period.

          -  Diagnosis of hypertension made during the screening period or current diagnosis of
             hypertension.

          -  Resting pulse of > 100 beats per minute or < 40 beats per minute during the screening
             period, either supine or standing.

          -  Positive testing for human immunodeficiency virus (HIV), hepatitis B and hepatitis C.

          -  Positive urine screen for drugs of abuse. In case of a positive result the urine
             screen for drugs of abuse may be repeated once at the discretion of the investigator.

          -  Positive pregnancy test (female subjects).

          -  Hemoglobin count deviating more than 10% of the lower limit of normal.

          -  Veins unsuitable for venous blood collection.

          -  Difficulty in swallowing.

          -  Any specific IMP safety concern.

          -  Vulnerable subjects, e.g., persons in detention.

          -  Employees or close relatives of the contract research organization, the sponsor, 3rd
             party vendors or affiliates of the above mentioned parties.