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A Study to Evaluate the Efficacy of FK949E in Bipolar Disorder Patients With Major Depressive Episodes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01725308
First received: November 8, 2012
Last updated: December 16, 2016
Last verified: December 2016
  Purpose
In period I, the treatment effect of FK949E was compared with that of placebo in a blind manner in bipolar disorder patients with major depressive episodes. In period II, the long-term safety and efficacy of FK949E was evaluated.

Condition Intervention Phase
Bipolar Disorder
Drug: FK949E
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II/III Study of FK949E — Placebo-controlled, Double-blind, Parallel-group Comparative Study and Open-label, Non-controlled Extension Study in Bipolar Disorder Patients With Major Depressive Episodes —

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Change From Baseline to End of Treatment Period I in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline and Week 8 ]
    The MADRS is a10-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:
  • Change From Baseline in MADRS Total Score [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 6, 8 ]
    The MADRS is a10-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.

  • Change From Baseline in Hamilton Depression Rating Scale (HAM-D17) Total Score [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 6, 8 ]
    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, where a higher score indicates a greater depressive state.

  • Change From Baseline in Clinical Global Impression-Bipolar Disorder-Severity (CGI-BP-S): Mania [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 6, 8 ]
    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 1 (not ill) to 7 (very severely ill).

  • Change From Baseline in CGI-BP-S: Depression [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 6, 8 ]
    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 (not ill) to 7 (very severely ill).

  • Change From Baseline in CGI-BP-S: Overall Bipolar Illness [ Time Frame: Baseline and Weeks 1, 2, 3, 4, 6, 8 ]
    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 (not ill) to 7 (very severely ill).

  • Clinical Global Impression-Bipolar Disorder-Change (CGI-BP-C): Mania [ Time Frame: Weeks 1, 2, 3, 4, 6, 8 ]
    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.

  • CGI-BP-C: Depression [ Time Frame: Weeks 1, 2, 3, 4, 6, 8 ]
    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.

  • CGI-BP-C: Overall Bipolar Illness [ Time Frame: Weeks 1, 2, 3, 4, 6, 8 ]
    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.

  • Number of Participants With Adverse Events [ Time Frame: up to 8 weeks ]
    An adverse event (AE) is defined as any undesirable or unintended sign (including abnormal 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.

  • Change From Baseline in Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS): Total Score [ Time Frame: Baseline and Weeks 4, 8 ]
    The DIEPSS is a scale used to evaluate drug-induced extrapyramidal symptoms. DIEPSS is composed of 8 individual symptom parameters and a global assessment of severity, each rated on a 5-point scale, with lower scores indicating as "normal." The DIEPSS total score ranges from 0 to 32, and excludes the global assessment of severity.

  • Change From Baseline in DIEPSS: Parkinsonism [ Time Frame: Baseline and Weeks 4, 8 ]
    The DIEPSS is a scale used to evaluate drug-induced extrapyramidal symptoms. DIEPSS is composed of 8 individual symptom parameters and a global assessment of severity, each rated on a 5-point scale, with lower scores indicating as "normal." Parkinsonism is a total of the gait disturbance, bradykinesia, salivation, muscle rigidity, and tremor scores and ranges from 0 to 20.

  • Change From Baseline in Young Mania Rating Scale (YMRS) [ Time Frame: Baseline and Weeks 1, 2, 3 4, 6, 8 ]
    The YMRS is a scale used to evaluate manic symptoms. The YMRS total score was the total assessment of assessed points for 11 items, ranges from 0 to 60 (each item is scored from either 0-4 or 0-8 by severity (0 = absent and 4/8 = displays mood/behavior to a greater degree). A lower score indicates "Absent" or "Normal."

  • Number of Participants With an Affirmative Response to Columbia Suicide Severity Rating Scale (C-SSRS): Suicidal Ideation [ Time Frame: Weeks 4, 8 ]
    The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 5 items for suicide ideation (1. Wish to be dead; 2. Suicidal thoughts; 3. Suicidal thoughts with a method (no specific plan or intent to act); 4. Suicidal intent (without a specific plan); 5. Suicidal intent with specific plan. If participants responded with a negative response for questions 1 and 2, the remaining questions are skipped. If question 2 was responded to with a positive response, the remaining questions need to be asked.

  • Number of Participants With an Affirmative Response to C-SSRS: Suicidal Behaviors [ Time Frame: Weeks 4, 8 ]
    The C-SSRS is a scale for assessing risk for suicidal behavior and suicide ideation and was administered by the clinician. Affirmative or negative responses were provided to 7 items to suicidal behaviors (1. suicide attempt; 2. Self-injury without suicide intent; 3. discontinued suicide attempt; 4. interrupted suicide attempt; 5. preliminary action to suicide; 6. suicidal behavior; 7. completed suicide).


Enrollment: 431
Study Start Date: February 2012
Study Completion Date: July 2016
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants who received placebo once daily at bedtime for 8 weeks in Treatment Period I.
Drug: Placebo
Taken by mouth (orally).
Experimental: FK949E 150 mg
After 2 days of up-titration, participants received FK949E 150 mg once daily at bedtime for 8 weeks in Treatment Period I.
Drug: FK949E
Taken by mouth (orally).
Other Name: quetiapine
Experimental: FK949E 300 mg
After 4 days of up-titration, participants received FK949E 300 mg once daily at bedtime for 8 weeks in Treatment Period I.
Drug: FK949E
Taken by mouth (orally).
Other Name: quetiapine

Detailed Description:
This study consisted of two parts. In Treatment Period I, FK949E or placebo was administered orally in a blind manner to bipolar disorder patients with major depressive episodes, with the aim of evaluating the superiority of FK949 over placebo and the dose response of two doses of FK949E based on changes in Montgomery-Asberg Depression Rating Scale (MADRS) total score. In Treatment Period II, the long-term safety, efficacy and pharmacokinetics of FK949E was evaluated in patients completed the Treatment Period I. Results are reported for Treatment Period I.
  Eligibility

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 Ver. 4 Text Revision (DSM-IV-TR,) with a major depressive episode
  • The Hamilton Depression Rating Scale (HAM-D17) total score of 20 points or more and HAM-D17 depressed mood score of 2 points or more
  • 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
  • History of abuse or dependence of alcohol or substances other than caffeine and nicotine
  • Treatment with a depot antipsychotic within the last 42 days before primary registration
  • Unable to stop taking mood stabilizers (lithium carbonate and/or sodium valproate), lamotrigine, antipsychotics, or antidepressants from 7 days before secondary registration
  • Unable to stop taking 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, after primary registration
  • Electroconvulsive therapy within the last 76 days before primary registration
  • The current major depressive episode persisting for more than 12 months or less than 4 weeks before informed consent
  • A possible need of psychotherapy during the study period (unless the therapy has been commenced at least 76 days before primary registration and been maintained on a fixed level at fixed frequency)
  • Documented or suspected conditions such as renal failure, hepatic failure, serious cardiac disease, hepatitis B, hepatitis C, or acquired immunodeficiency syndrome (AIDS) (or to be a carrier of hepatitis B, hepatitis C, or AIDS)
  • Concurrence of malignancy or history of cured malignancy within 5 years
  • Concurrence of uncontrolled hypertension (defined as a systolic blood pressure of 180 mmHg or more, or a diastolic blood pressure of 110 mmHg or more at primary registration) or unstable angina that may worsen with the study or may affect the study results based on the clinical judgment of the investigator or sub-investigator
  • Concurrence of hypotension (defined as a systolic blood pressure of less than 100 mmHg at primary registration) or orthostatic hypotension
  • History of transient, idiopathic orthostatic hypotension, with or without pre-syncope symptoms or syncope, or a current condition susceptible to transient hypotension, such as dehydration and decreased blood volume
  • Concurrent or previous history of cerebrovascular disease or transient ischemic attack (TIA)
  • Abnormal laboratory or electrocardiographic findings considered clinically significant in the investigator's or subinvestigator's opinion (in reference to grade 3 of the Adverse Drug Reactions Severity Grading Criteria [Notification No. 80 of the Safety Division, Pharmaceutical Affairs Bureau, Ministry of Health and Welfare dated 29 June 1992])
  • Participation in another clinical study or post-marketing study within the last 12 weeks before informed consent
  • History of quetiapine therapy during the current major depressive episode
  • Pregnant or lactating women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01725308

  Show 98 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Medical Director Astellas Pharma Inc
  More Information

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01725308     History of Changes
Other Study ID Numbers: 6949-CL-0021 
Study First Received: November 8, 2012
Results First Received: December 16, 2016
Last Updated: December 16, 2016

Keywords provided by Astellas Pharma Inc:
FK949E
Major depressive episode
patients

Additional relevant MeSH terms:
Disease
Bipolar Disorder
Depressive Disorder, Major
Depression
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Depressive Disorder
Mood Disorders
Behavioral Symptoms

ClinicalTrials.gov processed this record on February 24, 2017