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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Pharmacokinetics of Quetiapine
• Intervention / Treatment: Drug: FK949E; Drug: fluvoxamine

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kyushu, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 44 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FK949E group; receiving FK949E with and without fluvoxamine	Drug: FK949E; Oral; Other Names: extended release formulation of quetiapine; Drug: fluvoxamine; Oral; Other Names: Luvox®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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.

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): August 1, 2011
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: July 23, 2013
• First Submitted That Met QC Criteria: July 23, 2013
• First Posted (ESTIMATE): July 25, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Antipsychotic; Quetiapine; fluvoxamine; FK949E
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Quetiapine Fumarate; Fluvoxamine
• Other Study ID Numbers: 6949-CL-0004