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

Phase 1

Completed

• Conditions: Healthy; Pharmacokinetics of Quetiapine
• Interventions: Drug: FK949E; Drug: fluvoxamine

• Registration Number: NCT01908296
• Lead Sponsor: Astellas Pharma Inc

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-07
• Primary Completion: 2011-08
• Study Completion: 2011-08
• Study First Submitted: 2013-07-23
• Study First Submitted QC: 2013-07-23
• Study First Posted: 2013-07-25
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-14
• Last Update Posted: 2017-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FK949E group	FK949E	receiving FK949E with and without fluvoxamine
FK949E group	fluvoxamine	receiving FK949E with and without fluvoxamine

Primary Outcome Measures

Name	Time	Method
Maximum plasma concentration (Cmax) of unchanged quetiapine	For 48 hours after dosing.
AUC (area under the curve) of unchanged quetiapine	For 48 hours after dosing.

Secondary Outcome Measures

Name	Time	Method
tmax of plasma concentration of unchanged quetiapine	For 48 hours after dosing.
t1/2 of plasma concentration of unchanged quetiapine	For 48 hours after dosing.
Maximum plasma concentration (Cmax) of quetiapine metabolites	For 48 hours after dosing.
AUC (area under the curve) of quetiapine metabolites	For 48 hours after dosing.
tmax of plasma concentration of quetiapine metabolites	For 48 hours after dosing.
t1/2 of plasma concentration of quetiapine metabolites	For 48 hours after dosing.
Maximum plasma concentration (Cmax) of unchanged fluvoxamine	For 12 hours after dosing.
AUC (area under the curve) of unchanged fluvoxamine	For 12 hours after dosing.
tmax of plasma concentration of unchanged fluvoxamine	For 12 hours after dosing.
t1/2 of plasma concentration of unchanged fluvoxamine	For 12 hours after dosing.
Safety assessed by the incidence of adverse events, clinical tab tests, vital signs, 12-lead ECGs and physical exam	Up to 20 Days.