Study to Evaluate the Effect of Multiple-dose of Fluvoxamine on the Plasma Concentration of Quetiapine (FK949E) in Healthy Male Volunteers

Condition(s) targeted: Healthy; Pharmacokinetics of Quetiapine

Intervention: FK949E (Drug); fluvoxamine (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Astellas Pharma Inc

Official(s) and/or principal investigator(s):
Medical Director, Study Director, Affiliation: Astellas Pharma Inc

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.

Official title: Phase I Study of FK949E - A Study of Drug-drug Interactions Between FK949E and Fluvoxamine in Healthy Male Adults

Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Primary outcome:

Maximum plasma concentration (Cmax) of unchanged quetiapine

AUC (area under the curve) of unchanged quetiapine

Secondary outcome:

tmax of plasma concentration of unchanged quetiapine

t1/2 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.

Criteria:

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)

Kyushu, Japan

Starting date: July 2011
Last updated: July 23, 2013