Study to Evaluate the Effects of Switching Different Strength Forms of FK949E in Bipolar Disorder Patients With Major Depressive Episodes

• ClinicalTrials.gov Identifier: NCT02362412
• Recruitment Status: Completed
• First Posted: February 12, 2015
• Results First Posted: March 17, 2017
• Last Update Posted: February 8, 2019
• Sponsor: Astellas Pharma Inc
• Information provided by (Responsible Party): Astellas Pharma Inc

Study Description

Brief Summary:

The purpose of this study was to evaluate the efficacy, safety, and pharmacokinetics of switching FK949E (sustained-release quetiapine) 50-mg and 150-mg tablets to the other tablet at the equivalent total daily dose in bipolar disorder patients with major depressive episodes.

Condition or disease	Intervention/treatment	Phase
Bipolar Depression	Drug: FK949E	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of FK949E - An Open-label, Two-way Crossover Study to Evaluate the Effects of Switching Different Strength Forms of FK949E in Bipolar Disorder Patients With Major Depressive Episodes
• Actual Study Start Date: February 18, 2015
• Actual Primary Completion Date: February 6, 2016
• Actual Study Completion Date: February 6, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: FK949E 50 MG / FK949E 150 MG; Participants who received the 50 mg tablet once daily during Treatment Period II (8 weeks) and 150 mg tablet once daily during Treatment Period III (8 weeks).	Drug: FK949E; A tablet containing 50 mg or 150 mg of quetiapine taken orally.; Other Name: quetiapine
Experimental: FK949E 150 MG / FK949E 50 MG; Participants who received the 150 mg tablet once daily during Treatment Period II (8 weeks) and 50 mg tablet once daily during Treatment Period III (8 weeks).	Drug: FK949E; A tablet containing 50 mg or 150 mg of quetiapine taken orally.; Other Name: quetiapine

Outcome Measures

Primary Outcome Measures :

1. Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Week 8 of each treatment period (Week 12 and Week 20) ]
   The MADRS is a 10-item scale to measure the severity of depressive episodes, where each item is rated on a scale from 0 to 6. The MADRS total score ranges from 0 to 60 with lower scores indicating less depressive symptoms.

Secondary Outcome Measures :

1. Hamilton Depression Scale (HAM-D17) [ Time Frame: Week 8 of each treatment period (Week 12 and Week 20) ]
   The HAM-D17 is a clinician-rated 17-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 52 with lower scores indicating less depressive symptoms.
2. Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Overall Bipolar Illness [ Time Frame: Week 8 of each treatment period (Week 12 and Week 20) ]
   The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from with the scale from 1 (Normal, not ill) to 7 (very severely ill).
3. Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S):Depression [ Time Frame: Week 8 of each treatment period (Week 12 and Week 20) ]
   The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from with the scale from 1 (Normal, not ill) to 7 (very severely ill).
4. Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S): Mania [ Time Frame: Week 8 of each treatment period (Week 12 and Week 20) ]
   The CGI-BP-S is a scale which assesses a participant's severity of their overall bipolar illness, depression, and mania as assessed by the clinician using a scale from with the scale from 1 (Normal, not ill) to 7 (very severely ill)
5. Clinical Global Impression-Bipolar-Change (CGI-BP-C):Overall Bipolar Illness [ Time Frame: Week 8 of each treatment period (Week 12 and Week 20) ]
   The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.
6. Clinical Global Impression-Bipolar-Change (CGI-BP-C):Depression [ Time Frame: Week 8 of each treatment period (Week 12 and Week 20) ]
   The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.
7. Clinical Global Impression-Bipolar-Change (CGI-BP-C):Mania [ Time Frame: Week 8 of each treatment period (Week 12 and Week 20) ]
   The CGI-BP-C is a scale which assesses the degree of change or improvement from baseline for each of overall bipolar illness, depression and mania, by grading it using 8 grades, from 1 (very much improved) to 7 (very much worse) or 8 (not applicable). Grade 8 (not applicable) was regarded as a missing value for purposes of calculating the mean score.
8. Number of Participants With Adverse Events [ Time Frame: Up to 22 weeks ]
   An adverse event (AE) is defined as any undesirable or unintended sign (including abnonmal laboratory test values), symptom, or disease occurring while the study drug was administered, regardless of whether or not there was a causal relationship with the study drug. A serious AE is defined as a an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of bipolar I or II disorder as specified in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR), with a major depressive episode.
• Able to participate in the study with understanding of and compliance with subject requirements during the study in the investigator's or subinvestigator's opinion.

Exclusion Criteria:

• Concurrent or previous history of DSM-IV-TR Axis I disorders, except bipolar disorder, within the last 6 months before informed consent.
• Concurrence of DSM-IV-TR Axis II disorder that is considered to greatly affect patient's current mental status.
• The Young Mania Rating Scale (YMRS) total score of 13 points or more.
• Nine or more mood episodes within the last 12 months before informed consent.
• Lack of response to at least 6-week treatment with at least 2 antidepressants for the current major depressive episode in the investigator's or subinvestigator's opinion.
• The current major depressive episode persisting for less than 4 weeks before informed consent.
• History of substance dependence (other than caffeine and nicotine) or alcohol abuse or dependence.
• Treatment with a depot antipsychotic within the last 49 days before the start of the pre-treatment observation period.
• Unable to suspend antipsychotics or antidepressants after the start of the pre-treatment observation period.
• Treatment with more than one of the following three drugs, mood stabilizers (lithium carbonate and/or sodium valproate) and lamotrigine, if these drugs, except one of either drugs, cannot be suspended after the start of the pre-treatment observation period.
• Unable to suspend antiepileptics (except lamotrigine and sodium valproate), antianxiety agents, hypnotics, sedatives, psychostimulants, antiparkinsonian agents, cerebral ameliorators, antidementia agents, or anorectics, except those specified as conditionally-allowed concomitant drugs, from 7 days before the start of the pre-treatment observation period.
• Unable to suspend CYP3A4 inhibitors or inducers, or monoamine oxidase (MAO) inhibitors from 7 days before the start of the pre-treatment observation period.
• Electroconvulsive therapy within the last 83 days before the start of the pre-treatment observation period.
• A possible need of psychotherapy during the study period (unless the therapy has been commenced at least 83 days before the start of the pre-treatment observation period).
• The Hamilton Depression Rating Scale (HAM-D17) suicide score of 3 points or more, history of suicide attempt within the last 6 months before informed consent, or the risk of suicide in the investigator's or subinvestigator's opinion.

Contacts and Locations

Locations

Japan

Fukushima, Japan

Kanagawa, Japan

Kumamoto, Japan

Kyoto, Japan

Osaka, Japan

Tokushima, Japan

Tokyo, Japan

Sponsors and Collaborators

Astellas Pharma Inc

Investigators

• Study Director: Medical Director; Astellas Pharma Inc

More Information

Additional Information:

Link to results on Astellas Clinical Study Results website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fukushi R, Nomura Y, Katashima M, Komatsu K, Sato Y, Takada A. Approach to Evaluating QT Prolongation of Quetiapine Fumarate in Late Stage of Clinical Development Using Concentration-QTc Modeling and Simulation in Japanese Patients With Bipolar Disorder. Clin Ther. 2020 Aug;42(8):1483-1493.e1. doi: 10.1016/j.clinthera.2020.06.002. Epub 2020 Aug 11.

• Responsible Party: Astellas Pharma Inc
• ClinicalTrials.gov Identifier: NCT02362412
• Other Study ID Numbers: 6949-CL-0023
• First Posted: February 12, 2015
• Results First Posted: March 17, 2017
• Last Update Posted: February 8, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Keywords provided by Astellas Pharma Inc:

major depressive episodes; FK949E; quetiapine; bipolar depression; bipolar disorder

Additional relevant MeSH terms:

Depression; Bipolar Disorder; Behavioral Symptoms; Mental Disorders; Bipolar and Related Disorders; Quetiapine Fumarate; Antidepressive Agents; Psychotropic Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs