Schizophrenia
Conditions
Keywords
Schizophrenia
Brief summary
To evaluate the pharmacokinetics of oral multiple-dose of DWCZP tablet 100mg.
Detailed description
A randomized, 2-way crossover, open, phase I study to compare the pharmacokinetics profile of DWCZP tablet 100mg and Clozaril® tablet 100mg after a multiple-dose oral administration in schizophrenia patients.
Interventions
DRUGDWCZP
Multiple dose
DRUGClozaril
multiple-dose
Sponsors
The Catholic University of Korea
Konkuk University Hospital
Naju National Hospital
Seoul National Hospital
Wonkwang University
DongGuk University
Dong Wha Pharmaceutical Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Adult male or female within range of 20 to 60. * Diagnosed as Schizophrenia (Note: Diagnosed with DSM-IV, ICD-10 as a standard Schizophrenia diagnostic tool). * Administered clozapine for 3 months before signing agreement with same amount daily and who can administer clozapine 100mg twice (morning, evening) a day, total of 200mg during the study time. * One who might be pregnant must get negative result for pregnancy test (urine or blood β-hCG) before the randomization and during the study time, one must agree appropriate contraception. However, one who is using only hormone-contraceptive for birth control and has not been more that 1 year after Tubal ligation or menopause are excluded. * One who understood completed about this study after the explanation is given, decided to volunteer and gave written informed consent approved by IRB to participate in study in compliance with the requirement of the entire protocol.
Exclusion criteria
* One who has record of hypersensitive reaction with Clozapine or other antipsychotic drug. * WBC count less than 4,000/ml or Absolute Neutrophil count less than 2,000/ml. * Administering hypertension drug or has orthostatic hypotension. * One who has clinical problem with kidney or liver and include following criteria: CCr \< 50mL/min; BUN \> 30 mg/dl; ALT 또는 AST \> 3 x ULN; Total bilirubin \> 2 x ULN; ALP \> 2 x ULN. * Diagnosed to have other psychiatric or neurological problems other than Schizophrenia (e.g., Organic mental disorder, severe tardive dyskinesia, idiopathic Parkinson's disease, etc). * Record of Granulocytopenia or Myeloproliferative disorder in the past. * Record of stomach-related problems(active Crohn's disease, vital infectious intestine disease, ulcer, acute or chronic pancreatitis etc) or surgery which can affect absorption of study drug. However, simple appendectomy or herniotomy are exceptions. * Chronic Hepatitis B carrier, proof of Hepatitis C carrier or Hepatitis C antibody. * Immunodeficiency diseases such as HIV positive, AIDS, had bone marrow transplantation or has blood ammonia. * Record of seizure in 1 year before signing informed consent form or had administered anti-seizure drug before(e.g., Epilepsy, Convulsions, Myasthenia gravis, etc). * One who constantly drinks(\> 21Units/week, 1Unit = 10g of pure alcohol) or cannot stop drinking alcohol during hospitalization period. * Smoking past 3 months before signing informed consent form or cannot stop smoking during hospitalization period. * One who cannot attend routine blood tests. * Bone marrow malfunction. * Mental illness, durg addicted or in coma. * One who has any kind of circulation imperfection and patient with depressed central nervous system. * Major kidney and heart problem(e.g. myocarditis). * Incurable epilepsy. * Paralytic intestinal obstruction. * Generic problems such as Lactose intolerance, Galactose intolerance, Lapp lactose deficiency, Glucose-Galactose absorption deficiency, etc. * Administered barbital-related drugs and drug metabolizing enzyme inducer and inhibitor in 1 month before starting the study. * One who had drugs that can affect on result of the study for past 10 days before the study start. * One who had whole blood donation in 2 months or blood component donation or transfusion in 1 month before signing the informed consent form. * Attended clinical tests or bioequivalence tests in 2 months before signing informed consent form. * Currently pregnant or breast-feeding or has possibility of pregnancy because one is not using medically approved contraception(Note: condoms, oral contraceptive, intrauterine device, abstinence etc). * One who is clinically significant by observations considered as unsuitable based on medical judgement by investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Concentration of Clozapine in Plasma | Up to 12hours |
Secondary
| Measure | Time frame |
|---|---|
| Time to Reach Maximum Concentration of Clozapine in Plasma | Up to 12hours |
| Terminal Half Life of Clozapine in Plasma | Up to 12hours |
| Accumulation Rate of Clozapine in Plasma | Up tp 12hours |
Countries
South Korea
Participant flow
Recruitment details
Participants recruited from a specialty clinic at s hospital, in Seoul, Naju, Chungju, Iksan and Kyungju, Korea between June 2012 and March 2013
Pre-assignment details
32 participantsrecruited : 28 screened, 4 excluded(3 did not meet inclusion criteria and 1 refused participation)
Participants by arm
| Arm | Count |
|---|---|
| A Group DWCZP tablet 100mg twice daily in first intervention period and Clozaril tablet 100mg twice daily in second intervention period (no washout period, Intervention period : 10days) | 14 |
| B Group Clozaril tablet 100mg twice daily in first intervention period and DWCZP tablet 100mg twice daily in second intervention period (no washout period, Intervention period : 10days) | 14 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 1st Administration | Protocol Violation | 0 | 2 |
| 1st Administration | Withdrawal by Subject | 2 | 0 |
| 2nd Administration | Adverse Event | 1 | 0 |
| 2nd Administration | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | A Group | B Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 28 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 14 Participants | 28 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Korea, Republic of | 14 participants | 14 participants | 28 participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 14 | 4 / 14 |
| serious Total, serious adverse events | 1 / 14 | 0 / 14 |
Outcome results
Primary
Maximum Concentration of Clozapine in Plasma
Time frame: Up to 12hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A Group | Maximum Concentration of Clozapine in Plasma | 524.62 ng/mL | Standard Deviation 272.51 |
| B Group | Maximum Concentration of Clozapine in Plasma | 551.18 ng/mL | Standard Deviation 263.26 |
Secondary
Accumulation Rate of Clozapine in Plasma
Time frame: Up tp 12hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A Group | Accumulation Rate of Clozapine in Plasma | 2.01 ng/ml/hr | Standard Deviation 0.81 |
| B Group | Accumulation Rate of Clozapine in Plasma | 1.88 ng/ml/hr | Standard Deviation 0.44 |
Secondary
Terminal Half Life of Clozapine in Plasma
Time frame: Up to 12hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A Group | Terminal Half Life of Clozapine in Plasma | 11.98 hour | Standard Deviation 6.89 |
| B Group | Terminal Half Life of Clozapine in Plasma | 10.88 hour | Standard Deviation 3.81 |
Secondary
Time to Reach Maximum Concentration of Clozapine in Plasma
Time frame: Up to 12hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A Group | Time to Reach Maximum Concentration of Clozapine in Plasma | 2.43 hour | Standard Deviation 1.71 |
| B Group | Time to Reach Maximum Concentration of Clozapine in Plasma | 2.75 hour | Standard Deviation 1.93 |