Clinical trial NCT01908296: Study to Evaluate the Effect of Multiple-dose of Fluvoxamine on the Plasma Concentration of Quetiapine (FK949E) in Healthy Male Volunteers
Official title: Phase I Study of FK949E - A Study of Drug-drug Interactions Between FK949E and Fluvoxamine in Healthy Male Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Pharmacokinetics of Quetiapine
Keywords: FK949E
fluvoxamine
Antipsychotic
Quetiapine
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2013-07-25
Enrollment: 24
Sex: MALE
Minimum age (years): 20
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility 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)

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of unchanged quetiapine
timeFrame: For 48 hours after dosing.
measure: AUC (area under the curve) of unchanged quetiapine
timeFrame: For 48 hours after dosing.
Secondary outcomes:
measure: tmax of plasma concentration of unchanged quetiapine
timeFrame: For 48 hours after dosing.
measure: t1/2 of plasma concentration of unchanged quetiapine
timeFrame: For 48 hours after dosing.
measure: Maximum plasma concentration (Cmax) of quetiapine metabolites
timeFrame: For 48 hours after dosing.
measure: AUC (area under the curve) of quetiapine metabolites
timeFrame: For 48 hours after dosing.
measure: tmax of plasma concentration of quetiapine metabolites
timeFrame: For 48 hours after dosing.
measure: t1/2 of plasma concentration of quetiapine metabolites
timeFrame: For 48 hours after dosing.
measure: Maximum plasma concentration (Cmax) of unchanged fluvoxamine
timeFrame: For 12 hours after dosing.
measure: AUC (area under the curve) of unchanged fluvoxamine
timeFrame: For 12 hours after dosing.
measure: tmax of plasma concentration of unchanged fluvoxamine
timeFrame: For 12 hours after dosing.
measure: t1/2 of plasma concentration of unchanged fluvoxamine
timeFrame: For 12 hours after dosing.
measure: Safety assessed by the incidence of adverse events, clinical tab tests, vital signs, 12-lead ECGs and physical exam
timeFrame: Up to 20 Days.
Other outcomes:
Locations:
city: Kyushu
country: Japan
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: