The objective of the study was to assess the effect of multiple-dose fluvoxamine on the
pharmacokinetics of quetiapine (FK949E) in healthy adult male subjects. The safety of FK949E
in the population was also evaluated.
tmax of plasma concentration of unchanged quetiapinet1/2 of plasma concentration of unchanged quetiapine
Maximum plasma concentration (Cmax) of quetiapine metabolites
AUC (area under the curve) of quetiapine metabolites
tmax of plasma concentration of quetiapine metabolites
t1/2 of plasma concentration of quetiapine metabolites
Maximum plasma concentration (Cmax) of unchanged fluvoxamine
AUC (area under the curve) of unchanged fluvoxamine
tmax of plasma concentration of unchanged fluvoxamine
t1/2 of plasma concentration of unchanged fluvoxamine
Safety assessed by the incidence of adverse events, clinical tab tests, vital signs, 12-lead ECGs and physical exam
Minimum age: 20 Years.
Maximum age: 44 Years.
Gender(s): Male.
Inclusion Criteria:
- Body weight : ≥50. 0 kg, <80. 0 kg
- Body Mass Index : ≥17. 6, <26. 4
- Healthy, as judged by the investigator/subinvestigator based on the results of
physical examinations (subjective symptoms and objective findings) and all tests
obtained at screening and during the period from hospital admission to immediately
before study medication
Exclusion Criteria:
- Subjects with the following history.
1. Hepatic disease (e. g. viral hepatitis, drug-induced liver injury).
2. Heart disease (e. g. congestive heart failure, angina pectoris, arrhythmia
requiring treatment).
3. Respiratory disease (e. g. serious bronchial asthma, chronic bronchitis)
4. Gastrointestinal disease (e. g. serious peptic ulcer, gastroesophageal reflux
esophagitis; diseases requiring several selections except for appendicitis)
5. Renal disease (e. g. acute renal failure, glomerulonephritis, interstitial
nephritis).
6. Cerebrovascular disorder (e. g. cerebral infarction).
7. Malignant tumor.
8. Drug allergies. Allergic disorders (except for hay fever)
9. Drug dependence, alcohol dependence
- Any disease (except dental caries)
- A deviation from the normal reference range of blood pressure, pulse rate, body
temperature, or 12-lead ECG
- A deviation of the following criteria for clinical laboratory tests. The normal
reference ranges specified at the study site will be used as the normal reference
ranges in the present study.
1. Hematology:
- A deviation of ±20% from the upper or lower limit of the normal range
2. Blood biochemistry:
- A deviation from the normal range for AST, ALT, creatinine (Cre), HbA1c or
serum electrolytes.
- A deviation of ±20% from the upper or lower limit of the normal range for
other items than the above.
- However, the lower limit of the normal range will not be established for
items for which a deviation from the lower limit is not considered
clinically significant[AST, ALT, total bilirubin (T-Bil), ALP, γ-GTP, LDH,
CK, Cre, uric acid (UA), BUN, and total cholesterol (T-Cho)].
3. Urinalysis:
- U-Glc and/or U-Pro results of (±) or worse
- U-Uro results of (+) or worse
4. Urinary drug test:
- A positive result for phencyclidine, benzodiazepine, cocaine, amphetamines,
cannabis, opiates, barbiturates or tricyclic antidepressants
5. Immunological test:
- A positive result for hepatitis B, hepatitis C, syphilis, or HIV
- History of treatment, including medication, within 14 days before the start of study
drug administration
- Consumption of food or beverages containing St. John's Wort within 14 days before the
start of study drug administration, or consumption of grapefruit
- Previous participation in a pre- or post-marketing clinical study of another
prescription drug or a medical device within 120 days before the study
- History of administration of quetiapine
- History of administration of fluvoxamine
- Whole blood sampling of 400 mL or more within 90 days before the screening
assessment, whole blood sampling of 200 mL or more within 30 days before the
screening assessment, or blood component donation within 14 days before the screening
assessment
- Routine excessive alcohol consumption ("excessive alcohol" is defined as an average
of 45 g of alcohol per day [cf., a large bottle of beer containing 25 g of alcohol,
180 mL of sake containing 22 g of alcohol])
- Subjects with a smoking habit (except those who quit smoking at least 90 days before
the screening assessment)