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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
32
single dose, 2 mg Haloperidol tablet
single dose, 2 mg Haloperidol tablet
FARMOVS Clinical Research Organisation
Bloemfontein, Free State, South Africa
Concentration Maximum (Cmax)
The maximum observed concentration of haloperidol as measured by bioanalysis of the blood plasma is referred to as the 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
Area Under the Curve (0-t) (AUC(0-t))
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.
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
Area Under the Curve(0-∞) (AUC(0-∞))
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-∞).
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 to Maximum Concentration (Tmax)
The timepoint at which the maximum concentration of haloperidol as measured by bioanalysis of the blood plasma is observed.
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
Terminal Elimination Rate Constant (λz)
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.
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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
Terminal Elimination Half-life (t½)
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.
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