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Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00797966
Collaborator
(none)
850
Enrollment
50
Locations
2
Arms
14
Duration (Months)
17
Patients Per Site
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary: To compare the efficacy of OPC-34712 to placebo as adjunctive treatment to an assigned open-label marketed antidepressant treatment (ADT)in patients who demonstrate an incomplete response to a prospective eight week trial of the same assigned open-label marketed ADT.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

A comparison of the Fixed dose arm (OPC-31712, 0.15 mg) verses placebo was included as a general secondary efficacy variable and results for this dose group comparison are included under each of the Outcome Measures.

Study Design

Study Type:
Interventional
Actual Enrollment :
850 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
Study Start Date :
May 1, 2009
Actual Primary Completion Date :
Jun 1, 2010
Actual Study Completion Date :
Jul 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

OPC-34712 + ADT

Drug: OPC-34712
Tablets, Oral, 1 - 4 mg OPC-34712 variable dose once daily, 14 weeks
Other Names:
  • Generic Name: Brexpiprazole

    • Drug: ADT
    Tablets, 10 - 225 mgs, dose once daily, 14 weeks
    Other Names:
  • Each individual will receive one of the following 6 ADTs:
  • Escitalopram (Lexapro)
  • Fluoxetine (Prozac)
  • Paroxetine CR (Paxil CR)
  • Sertraline (Zoloft)
  • Desvenlafaxine (Pristiq)
  • Venalfaxine XR (Effexor XR)

    		•
    Placebo Comparator: 2

    Placebo + ADT

    Drug: Placebo
    Tablets, Oral, 1- 4 mg OPC-34712 once daily, 14 weeks

    Drug: ADT
    Tablets, 10 - 225 mgs, dose once daily, 14 weeks
    Other Names:
  • Each individual will receive one of the following 6 ADTs:
  • Escitalopram (Lexapro)
  • Fluoxetine (Prozac)
  • Paroxetine CR (Paxil CR)
  • Sertraline (Zoloft)
  • Desvenlafaxine (Pristiq)
  • Venalfaxine XR (Effexor XR)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score. [Week 8 to Week 14]

      The MADRS is utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60. The MADRS Total Score was unevaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items were recorded, the MADRS Total Score was the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.

    Secondary Outcome Measures

    1. Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. [Week 8 to Week 14]

      CGI-S items are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale from 1 through 7. CGI-S was assessed at screening, baseline and each subsequent visit from Week 1 through Week 14.

    2. Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Quality of Life, Enjoyment, and Satisfaction Questionnaire - Short Form (QLES-Q-SF) Subscale Score - the Overall General Subscore (Sum of First 14 Items). [Week 8 to Week 14]

      The Q-LES-Q is a self-report measure to enable physicians to obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. The Overall-General Subscore will be defined by summing the scores on all 14 items and expressing it as the percent of the maximum possible score. When expressing the total score as a percentage, if items are left blank the range will be modified to reflect the number of items scored. Raw score is sum of non-missing ratings from items 1 to 14. Minimum score is number of non-missing items. Maximum score is 5*(minimum score). Range is maximum score minus minimum score. Total score is 100*(Raw score minus minimum score)/ Range, rounded to nearest integer.

    3. Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Score (the Mean of 3 Individual Item Scores). [Week 8 to Week 14]

      The Sheehan Disability Scale (SDS) is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.

    4. Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit. [Week 8 to each of Week 9, 10, 11, 12 and 13.]

      The MADRS is utilized as the primary efficacy assessment of a patient's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60. The MADRS Total Score was unevaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items were recorded, the MADRS Total Score was the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.

    5. Change From End of Phase A (Week 8 Visit) in Mean CGI-S Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit. [Week 8 to each of Week 9, 10, 11, 12 and 13.]

      CGI-S items are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale from 1 through 7. CGI-S was assessed at screening, baseline and each subsequent visit from Week 1 through Week 14.

    6. Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 15 Score (Satisfaction With Medication). [Week 8 to Week 14]

      The Q-LES-Q (Short Form) is a self-report measure designed to enable physicians to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. According to the scoring system suggested for this questionnaire, item 15 (Satisfaction with Medication) will yield a separate subscore.

    7. Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 16 Score (Overall Life Satisfaction). [Week 8 to Week 14]

      The Q-LES-Q (Short Form) is a self-report measure designed to enable physicians to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. According to the scoring system suggested for this questionnaire, item 16 (Overall Life Satisfaction) will yield a separate subscore.

    8. Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score. [Week 8 to each of Week 9, 10, 11, 12, 13 and 14]

      The IDS-SR is a 30-item self-report measure used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorders. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the "best" rating and 3 being the "worst" rating. The IDS-SR Total Score is the sum of ratings of 28 item scores. The possible IDS-SR Total Score ranges from 0 to 84. The IDS-SR Total Score was un-evaluable if less than 23 of the 28 items are recorded. If the number of items was at least 23 and at most 27, the IDS-SR Total Score will be the mean of the recorded items multiplied by 28 and then rounded to the first decimal place.

    9. Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Depression Rating Scale (HAM-D17) Score. [Week 8 to Week 14]

      The HAM-D17 is utilized as a secondary assessment of a participant's level of depression. The HAM-D (17-Item) consists of 17 items. Eight items are rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the "best" rating and the highest score (2 or 4) is the "worst" rating. The possible total scores are from 0 to 52.

    10. Clinical Global Impression-Improvement Scale (CGI-I) Score at Each Study Week Visit in Phase B. [Week 8 to each of Week 9, 10, 11, 12, 13 and 14.]

      CGI-I items are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. CGI-I was assessed at each visit in Phase B, and improvement is judged with respect to the participant's condition at baseline. CGI-I was also assessed at each visit in Phase B, but in that phase improvement is judged with respect to the partcipant's condition at the end of Phase A.

    11. Percentage of Participants With MADRS Response From End of Phase A (Week 8 Visit). [Week 8 to each of Week 9, 10, 11, 12, 13 and 14.]

      A MADRS response was defined as >/= 50% reduction in MADRS Total Score from end of Phase A (Week 8 visit).

    12. Percentage of Participants With MADRS Remission From End of Phase A (Week 8 Visit). [Week 8 to each of Week 9, 10, 11, 12, 13 and 14.]

      A MADRS remission was defined as MADRS Total Score </= 10 and >/= 50% reduction in MADRS Total Score from end of Phase A (Week 8 visit).

    13. Percentage of Participants With CGI-I Response From End of Phase A (Week 8 Visit). [Week 9, 10, 11, 12, 13 and 14.]

      CGI-I response is defined as CGI-I of 1 [very much improved] or 2 [much improved].

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female subjects between 18 and 65 years of age, with diagnosis of major depressive disorder, as defined by DSM-IV-TR criteria

    • The current depressive episode must be equal to or greater than 8 weeks in duration

    • Subjects must report a history for the current depressive episode of an inadequate response to at least one and no more than three adequate antidepressant treatments.

    Exclusion Criteria:

    • Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug.

    • Subjects who report an inadequate response to more than three adequate trials of antidepressant treatments during current depressive episode at a therapeutic dose for an adequate duration.

    • Subjects with a current Axis I (DSM-IV-TR) diagnosis of:

    • Delirium, dementia,amnestic or other cognitive disorder

    • Schizophrenia, schizoaffective disorder, or other psychotic disorder

    • Bipolar I or II disorder

    • Subjects with a clinically significant current Axis II (DSM-IV-TR)

    • diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pacific Clinical Research Medical Group Arcadia California United States 91007
    2 Southwestern Research Beverly Hills California United States 90210
    3 Synergy Escondido Escondido California United States 92025
    4 Collaborative Neuroscience Network Inc. Garden Grove California United States 92845
    5 Synergy Clinical Research Center National City California United States 91950
    6 Excell Research Oceanside California United States 92056
    7 Affiliated Research Institute San Diego California United States 92108
    8 California Neuroscience Research Medical Group, Inc. Sherman Oaks California United States 91403
    9 Radiant Research Center Denver Colorado United States 80239
    10 Florida Clinical Research Center, LLC Bradenton Florida United States 34208
    11 CNS Clinical Research Group Coral Springs Florida United States 33065
    12 Gulfcoast Clinical Research Center Fort Myers Florida United States 33912
    13 Clinical Neuroscience Solutions, Inc. Jacksonville Florida United States 32216
    14 Accurate Clinical Trials Kissimee Florida United States 34741
    15 Clinical Neurosciences Solutions Orlando Florida United States 32806
    16 Stedman Clinical Trials Tampa Florida United States 33613
    17 University of South Florida College of Medicine Psychiatry Center Tampa Florida United States 33613
    18 Janus Center West Palm Beach Florida United States 33407
    19 Carman Research Smyrna Georgia United States 30080
    20 Uptown Research Institute Chicago Illinois United States 60640
    21 Midwest Center for Neurobehavioral Medicine Oakbrook Terrace Illinois United States 60181
    22 The Davis Clinic, PC Indianapolis Indiana United States 46260
    23 Vince & Associates Clinical Research Overland Park Kansas United States 66212
    24 Pharmasite Research, Inc. Baltimore Maryland United States 21208
    25 Bioscience Research Mount Kisco New York United States 10549
    26 Eastside Comprehensive Medical Center New York City New York United States 10021
    27 Medical & Behavioral Health Research, PC New York New York United States 10023
    28 Finger Lakes Clinical Research Rochester New York United States 14618
    29 Carolinas HealthCare - Behavioral Heath Center Charlotte North Carolina United States 28211
    30 NorthCoast Clinical Trials, Inc Beachwood Ohio United States 44122
    31 Neuro-Behavioral Clinical Research, Inc Canton Ohio United States 44718
    32 Patient Priority Clinical Sites, LLC Cinncinnati Ohio United States 45242
    33 Midwest Clinical Research Center Dayton Ohio United States 45408
    34 NorthStar Medical Research, LLC Middleburg Heights Ohio United States 44130
    35 Summitt Research Network (Oregon) Portland Oregon United States 97210
    36 Suburban Research Associates Media Pennsylvania United States 19063
    37 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    38 USC School of Medicine- Department of Neuropsychiatry and Behavioral Science Columbia South Carolina United States 29203
    39 Clinical Neurosciences Solutions, Inc. Memphis Tennessee United States 38119
    40 Community Clinical Research, Inc. Austin Texas United States 78754
    41 FutureSearch Clinical Trials Austin Texas United States 78756
    42 Radiant Research Salt Lake City Utah United States 84107
    43 Mood Disorders Clinic Salt Lake City Utah United States 84132
    44 Psychiatric Alliance of the Blue Ridge Charlottesville Virginia United States 22903
    45 NeuroScience, Inc. Herndon Virginia United States 20170
    46 Dominion Clinical Research Midlothian Virginia United States 23112
    47 Northwest Clinical Research Center Bellevue Washington United States 98007
    48 Summit Research Network (Seattle) LLC Seattle Washington United States
    49 Northbrooke Research Center Brown Deer Wisconsin United States 53223
    50 Dean Foundation Middleton Wisconsin United States 53562

    Sponsors and Collaborators

    • Otsuka Pharmaceutical Development & Commercialization, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Otsuka Pharmaceutical Development & Commercialization, Inc.
    ClinicalTrials.gov Identifier:
    NCT00797966
    Other Study ID Numbers:
    • 331-08-211
    First Posted:
    Nov 25, 2008
    Last Update Posted:
    Feb 29, 2016
    Last Verified:
    Feb 1, 2016
    Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.
    OPC-34712, Major Depressive Disorder, Adjunctive Treatment
    Additional relevant MeSH terms:
    Disease
    Depressive Disorder
    Depression
    Depressive Disorder, Major
    Citalopram
    Fluoxetine
    Paroxetine
    Sertraline
    Desvenlafaxine Succinate
    Brexpiprazole

    Study Results

    Participant Flow

    Recruitment Details This study was a Phase 2, multicenter, randomized, double-blind, placebo-controlled study of the safety and efficacy of OPC-34712 as adjunctive therapy in the treatment of participants with major depressive disorder. This study was conducted in the United States at 50 study centers.
    Pre-assignment Detail The study consisted of a 28-day Screening period, an 8-Week single-blind placebo + Antidepressant therapy (ADT) prospective Phase A. A 6-week double-blind Randomization Phase (Phase B) or single-blind Phase A+ for those participants who did not meet criteria for randomization and a Follow-up of 30 (+2) days after the last dose of study medication.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo Participants in Phase A Participants in Phase A+
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. Participants entered Phase A (single-blind prospective treatment) during which participants had received single-blind placebo plus an open-label commercially available ADT for 8 weeks at maximally tolerated doses. Based on the response at Week 8 (in Phase A), participants were either randomized to Phase B or continued single-blind treatment in Phase A+. Participants who met the criteria for a response at Week 8 were not to be randomized into Phase B but continued to receive single-blind placebo plus the maximum tolerated dose of ADT from Week 8 for an additional 6 weeks in Phase A+.
    Period Title: Phase A
    STARTED 0 0 0 0 849 0
    COMPLETED 0 0 0 0 664 0
    NOT COMPLETED 0 0 0 0 185 0
    Period Title: Phase A
    STARTED 62 120 121 126 0 0
    COMPLETED 51 102 100 110 0 0
    NOT COMPLETED 11 18 21 16 0 0
    Period Title: Phase A
    STARTED 0 0 0 0 0 235
    COMPLETED 0 0 0 0 0 207
    NOT COMPLETED 0 0 0 0 0 28

    Baseline Characteristics

    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo Total
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. Total of all reporting groups
    Overall Participants 62 120 121 126 429
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    43.9
    (10.8)
    44.0
    (11.8)
    43.7
    (11.6)
    43.3
    (11.5)
    43.7
    (11.5)
    Sex: Female, Male (Count of Participants)
    Female
    41
    66.1%
    86
    71.7%
    80
    66.1%
    82
    65.1%
    289
    67.4%
    Male
    21
    33.9%
    34
    28.3%
    41
    33.9%
    44
    34.9%
    140
    32.6%

    Outcome Measures

    1. Primary Outcome
    Title Change From the End of Phase A (Week 8 Visit) to the End of Phase B (Week 14 Visit) in Montgomery Asberg Depression Rating Scale (MADRS) Total Score.
    Description The MADRS is utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60. The MADRS Total Score was unevaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items were recorded, the MADRS Total Score was the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.
    Time Frame Week 8 to Week 14

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat (ITT) dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The Last Observation Carried Forward (LOCF) method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Least Squares Mean (Standard Error) [Units on a scale]
    -6.62
    (0.99)
    -6.46
    (0.73)
    -8.23
    (0.74)
    -6.09
    (0.72)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments The planned sample size of 120 participants per arm will yield 80% power to detect the treatment effects at a 2-tailed significance level of 0.025. The 0.025 significance level corresponds to the second level of Hochberg's procedure for handling the two primary efficacy comparisons.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6551
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.53
    Confidence Interval (2-Sided) 95%
    -2.87 to 1.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments The planned sample size of 120 participants per arm will yield 80% power to detect the treatment effects at a 2-tailed significance level of 0.025. The 0.025 significance level corresponds to the second level of Hochberg's procedure for handling the two primary efficacy comparisons.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7037
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.37
    Confidence Interval (2-Sided) 95%
    -2.30 to 1.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments The planned sample size of 120 participants per arm will yield 80% power to detect the treatment effects at a 2-tailed significance level of 0.025. The 0.025 significance level corresponds to the second level of Hochberg's procedure for handling the two primary efficacy comparisons.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0303
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.14
    Confidence Interval (2-Sided) 95%
    -4.08 to -0.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.
    Description CGI-S items are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale from 1 through 7. CGI-S was assessed at screening, baseline and each subsequent visit from Week 1 through Week 14.
    Time Frame Week 8 to Week 14

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Least Squares Mean (Standard Error) [Units on a scale]
    -0.83
    (0.13)
    -0.81
    (0.10)
    -1.06
    (0.10)
    -0.71
    (0.09)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4166
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4193
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.10
    Confidence Interval (2-Sided) 95%
    -0.35 to 0.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0064
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.35
    Confidence Interval (2-Sided) 95%
    -0.60 to -0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    3. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Quality of Life, Enjoyment, and Satisfaction Questionnaire - Short Form (QLES-Q-SF) Subscale Score - the Overall General Subscore (Sum of First 14 Items).
    Description The Q-LES-Q is a self-report measure to enable physicians to obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. The Overall-General Subscore will be defined by summing the scores on all 14 items and expressing it as the percent of the maximum possible score. When expressing the total score as a percentage, if items are left blank the range will be modified to reflect the number of items scored. Raw score is sum of non-missing ratings from items 1 to 14. Minimum score is number of non-missing items. Maximum score is 5*(minimum score). Range is maximum score minus minimum score. Total score is 100*(Raw score minus minimum score)/ Range, rounded to nearest integer.
    Time Frame Week 8 to Week 14

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 61 112 113 120
    Least Squares Mean (Standard Error) [Percentage of maximum possible score]
    7.60
    (1.82)
    6.53
    (1.38)
    7.46
    (1.38)
    5.92
    (1.34)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4490
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.68
    Confidence Interval (2-Sided) 95%
    -2.67 to 6.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7412
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.61
    Confidence Interval (2-Sided) 95%
    -3.02 to 4.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4070
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.54
    Confidence Interval (2-Sided) 95%
    -2.10 to 5.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    4. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Score (the Mean of 3 Individual Item Scores).
    Description The Sheehan Disability Scale (SDS) is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.
    Time Frame Week 8 to Week 14

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination
    Measure Participants 61 111 113 120
    Least Squares Mean (Standard Error) [Units on a scale]
    -0.84
    (0.27)
    -0.80
    (0.21)
    -1.27
    (0.20)
    -0.61
    (0.20)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4954
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.22
    Confidence Interval (2-Sided) 95%
    -0.86 to 0.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4902
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -0.73 to 0.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0161
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.66
    Confidence Interval (2-Sided) 95%
    -1.20 to -0.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    5. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit.
    Description The MADRS is utilized as the primary efficacy assessment of a patient's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60. The MADRS Total Score was unevaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items were recorded, the MADRS Total Score was the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.
    Time Frame Week 8 to each of Week 9, 10, 11, 12 and 13.

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Week 9 (N=61,117,116,121)
    -2.13
    (5.22)
    -3.00
    (5.13)
    -2.75
    (5.32)
    -2.48
    (5.43)
    Week 10 (N=62,119,118,126)
    -3.69
    (5.34)
    -3.78
    (6.27)
    -4.97
    (6.48)
    -3.64
    (6.65)
    Week 11 (N=62,119,118,126)
    -5.53
    (7.24)
    -5.71
    (7.15)
    -5.88
    (7.09)
    -4.40
    (7.05)
    Week 12 (N=62,119,118,126)
    -6.97
    (7.65)
    -6.31
    (6.72)
    -7.01
    (7.58)
    -4.41
    (6.74)
    Week 13 (N=62,119,118,126)
    -6.90
    (7.71)
    -6.76
    (7.20)
    -7.18
    (7.64)
    -5.47
    (7.47)
    6. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) in Mean CGI-S Score for Every Study Week Visit in Phase B Other Than the Week 14 Visit.
    Description CGI-S items are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) was set to missing. The CGI-S was therefore a 7-point scale from 1 through 7. CGI-S was assessed at screening, baseline and each subsequent visit from Week 1 through Week 14.
    Time Frame Week 8 to each of Week 9, 10, 11, 12 and 13.

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Week 9 (N=62,117,116,121)
    -0.21
    (0.60)
    -0.26
    (0.57)
    -0.33
    (0.64)
    -0.21
    (0.58)
    Week 10 (N=62,119,118,126)
    -0.42
    (0.74)
    -0.39
    (0.77)
    -0.61
    (0.91)
    -0.40
    (0.87)
    Week 11 (N=62,119,118,126)
    -0.53
    (0.95)
    -0.53
    (0.84)
    -0.69
    (0.92)
    -0.47
    (0.89)
    Week 12 (N=62,119,118,126)
    -0.76
    (1.02)
    -0.66
    (0.87)
    -0.86
    (1.00)
    -0.52
    (0.98)
    Week 13 (N=62,119,118,126)
    -0.74
    (1.09)
    -0.78
    (0.95)
    -0.88
    (1.01)
    -0.59
    (1.04)
    7. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 15 Score (Satisfaction With Medication).
    Description The Q-LES-Q (Short Form) is a self-report measure designed to enable physicians to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. According to the scoring system suggested for this questionnaire, item 15 (Satisfaction with Medication) will yield a separate subscore.
    Time Frame Week 8 to Week 14

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 61 111 113 120
    Mean (Standard Deviation) [Units on a scale]
    0.02
    (0.22)
    0.01
    (0.25)
    0.02
    (0.33)
    0.00
    (0.22)
    8. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Mean Q-LES-Q-SF Item 16 Score (Overall Life Satisfaction).
    Description The Q-LES-Q (Short Form) is a self-report measure designed to enable physicians to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning. Each item is scored on a five-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. Lower scores indicating less enjoyment or satisfaction with the activity. According to the scoring system suggested for this questionnaire, item 16 (Overall Life Satisfaction) will yield a separate subscore.
    Time Frame Week 8 to Week 14

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 61 112 113 120
    Mean (Standard Deviation) [Units on a scale]
    0.30
    (0.84)
    0.30
    (0.79)
    0.35
    (0.93)
    0.28
    (1.00)
    9. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score.
    Description The IDS-SR is a 30-item self-report measure used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorders. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the "best" rating and 3 being the "worst" rating. The IDS-SR Total Score is the sum of ratings of 28 item scores. The possible IDS-SR Total Score ranges from 0 to 84. The IDS-SR Total Score was un-evaluable if less than 23 of the 28 items are recorded. If the number of items was at least 23 and at most 27, the IDS-SR Total Score will be the mean of the recorded items multiplied by 28 and then rounded to the first decimal place.
    Time Frame Week 8 to each of Week 9, 10, 11, 12, 13 and 14

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Week 9 (N=61, 117,116,121)
    -0.98
    (7.28)
    -1.88
    (6.60)
    -2.04
    (5.93)
    -0.98
    (7.58)
    Week 10 (N=62, 119, 118, 126)
    -2.13
    (8.02)
    -2.58
    (7.37)
    -4.08
    (7.25)
    -1.62
    (7.76)
    Week 11 (N=62, 119, 118, 126)
    -3.58
    (7.81)
    -3.41
    (7.88)
    -4.82
    (7.96)
    -2.09
    (8.42)
    Week 12 (N=62, 119, 118, 126)
    -5.11
    (9.42)
    -3.77
    (8.45)
    -5.77
    (9.26)
    -2.07
    (8.42)
    Week 13 (N=62, 119, 118, 126)
    -5.34
    (9.15)
    -5.22
    (8.72)
    -5.65
    (8.84)
    -2.37
    (8.45)
    Week 14 (N=62, 119, 118, 126)
    -5.55
    (9.65)
    -4.96
    (9.37)
    -6.74
    (9.76)
    -3.08
    (9.32)
    10. Secondary Outcome
    Title Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Depression Rating Scale (HAM-D17) Score.
    Description The HAM-D17 is utilized as a secondary assessment of a participant's level of depression. The HAM-D (17-Item) consists of 17 items. Eight items are rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the "best" rating and the highest score (2 or 4) is the "worst" rating. The possible total scores are from 0 to 52.
    Time Frame Week 8 to Week 14

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 48 98 101 109
    Least Squares Mean (Standard Error) [Units on a scale]
    -5.77
    (0.86)
    -5.28
    (0.63)
    -6.59
    (0.62)
    -5.23
    (0.59)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5953
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.54
    Confidence Interval (2-Sided) 95%
    -2.54 to 1.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9479
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.05
    Confidence Interval (2-Sided) 95%
    -1.66 to 1.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0919
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.36
    Confidence Interval (2-Sided) 95%
    -2.95 to 0.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment difference = difference in adjusted mean change: OPC-34712 - placebo.
    11. Secondary Outcome
    Title Clinical Global Impression-Improvement Scale (CGI-I) Score at Each Study Week Visit in Phase B.
    Description CGI-I items are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. CGI-I was assessed at each visit in Phase B, and improvement is judged with respect to the participant's condition at baseline. CGI-I was also assessed at each visit in Phase B, but in that phase improvement is judged with respect to the partcipant's condition at the end of Phase A.
    Time Frame Week 8 to each of Week 9, 10, 11, 12, 13 and 14.

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Week 9 (N=62, 117, 116, 121)
    3.39
    (0.86)
    3.30
    (0.79)
    3.20
    (0.80)
    3.31
    (0.79)
    Week 10 (N=62, 119, 118, 126)
    3.16
    (0.94)
    3.19
    (0.90)
    2.95
    (0.93)
    3.11
    (1.04)
    Week 11 (N=62, 119, 118, 126)
    2.94
    (0.94)
    3.02
    (0.98)
    2.80
    (0.92)
    2.94
    (1.01)
    Week 12 (N=62, 119, 118, 126)
    2.87
    (1.06)
    2.90
    (0.99)
    2.70
    (1.03)
    2.95
    (1.06)
    Week 13 (N=62, 119, 118, 126)
    2.85
    (1.13)
    2.76
    (1.02)
    2.64
    (1.06)
    2.90
    (1.14)
    Week 14 (N=62, 119, 118, 126)
    2.74
    (1.16)
    2.78
    (1.02)
    2.52
    (1.08)
    2.83
    (1.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3998
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8838
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4012
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6131
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5964
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2540
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8524
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6969
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3108
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8719
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6105
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0709
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9574
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2310
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0672
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8441
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6741
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0183
    Comments Cochran-Mantel-Haenszel row mean scores differ test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    12. Secondary Outcome
    Title Percentage of Participants With MADRS Response From End of Phase A (Week 8 Visit).
    Description A MADRS response was defined as >/= 50% reduction in MADRS Total Score from end of Phase A (Week 8 visit).
    Time Frame Week 8 to each of Week 9, 10, 11, 12, 13 and 14.

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Week 9 (N=61, 117, 116, 121)
    4.92
    7.9%
    6.84
    5.7%
    2.59
    2.1%
    8.26
    6.6%
    Week 10 (N=62, 119, 118, 126)
    8.06
    13%
    8.40
    7%
    11.0
    9.1%
    9.52
    7.6%
    Week 11 (N=62, 119, 118, 126)
    19.4
    31.3%
    15.1
    12.6%
    18.6
    15.4%
    13.5
    10.7%
    Week 12 (N=62, 119, 118, 126)
    30.6
    49.4%
    15.1
    12.6%
    25.4
    21%
    11.9
    9.4%
    Week 13 (N=62, 119, 118, 126)
    24.2
    39%
    22.7
    18.9%
    25.4
    21%
    18.3
    14.5%
    Week 14 (N=62, 119, 118, 126)
    27.4
    44.2%
    20.2
    16.8%
    34.7
    28.7%
    19.8
    15.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3007
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.49
    Confidence Interval (2-Sided) 95%
    0.12 to 1.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8812
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.94
    Confidence Interval (2-Sided) 95%
    0.42 to 2.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0553
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.32
    Confidence Interval (2-Sided) 95%
    0.10 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6051
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.78
    Confidence Interval (2-Sided) 95%
    0.30 to 2.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8264
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.92
    Confidence Interval (2-Sided) 95%
    0.46 to 1.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8690
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.54 to 2.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3441
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.35
    Confidence Interval (2-Sided) 95%
    0.74 to 2.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6375
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.14
    Confidence Interval (2-Sided) 95%
    0.67 to 1.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3135
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.31
    Confidence Interval (2-Sided) 95%
    0.78 to 2.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0035
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 2.35
    Confidence Interval (2-Sided) 95%
    1.32 to 4.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4358
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.27
    Confidence Interval (2-Sided) 95%
    0.70 to 2.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0063
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 2.02
    Confidence Interval (2-Sided) 95%
    1.20 to 3.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3968
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.27
    Confidence Interval (2-Sided) 95%
    0.72 to 2.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2990
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.27
    Confidence Interval (2-Sided) 95%
    0.81 to 2.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1614
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.39
    Confidence Interval (2-Sided) 95%
    0.86 to 2.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3254
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.29
    Confidence Interval (2-Sided) 95%
    0.79 to 2.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9463
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.64 to 1.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0080
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.74
    Confidence Interval (2-Sided) 95%
    1.14 to 2.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title Percentage of Participants With MADRS Remission From End of Phase A (Week 8 Visit).
    Description A MADRS remission was defined as MADRS Total Score </= 10 and >/= 50% reduction in MADRS Total Score from end of Phase A (Week 8 visit).
    Time Frame Week 8 to each of Week 9, 10, 11, 12, 13 and 14.

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Week 9 (N=61, 117, 116, 121)
    3.28
    5.3%
    1.71
    1.4%
    1.72
    1.4%
    4.13
    3.3%
    Week 10 (N=62, 119, 118, 126)
    8.06
    13%
    5.04
    4.2%
    10.2
    8.4%
    8.73
    6.9%
    Week 11 (N=62, 119, 118, 126)
    12.9
    20.8%
    10.1
    8.4%
    14.4
    11.9%
    11.1
    8.8%
    Week 12 (N=62, 119, 118, 126)
    21.0
    33.9%
    10.1
    8.4%
    19.5
    16.1%
    10.3
    8.2%
    Week 13 (N=62, 119, 118, 126)
    19.4
    31.3%
    16.8
    14%
    15.3
    12.6%
    15.1
    12%
    Week 14 (N=62, 119, 118, 126)
    22.6
    36.5%
    15.1
    12.6%
    23.7
    19.6%
    13.5
    10.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5791
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.59
    Confidence Interval (2-Sided) 95%
    0.09 to 3.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2653
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.43
    Confidence Interval (2-Sided) 95%
    0.10 to 1.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2259
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.39
    Confidence Interval (2-Sided) 95%
    0.08 to 1.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6986
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.83
    Confidence Interval (2-Sided) 95%
    0.32 to 2.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2339
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.61
    Confidence Interval (2-Sided) 95%
    0.28 to 1.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8615
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.07
    Confidence Interval (2-Sided) 95%
    0.53 to 2.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8807
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.51 to 2.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9035
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.96
    Confidence Interval (2-Sided) 95%
    0.52 to 1.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5898
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.19
    Confidence Interval (2-Sided) 95%
    0.64 to 2.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0840
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.82
    Confidence Interval (2-Sided) 95%
    0.93 to 3.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9115
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.96
    Confidence Interval (2-Sided) 95%
    0.49 to 1.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0522
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.77
    Confidence Interval (2-Sided) 95%
    0.98 to 3.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4997
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.24
    Confidence Interval (2-Sided) 95%
    0.65 to 2.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5846
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.16
    Confidence Interval (2-Sided) 95%
    0.69 to 1.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9602
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 0.99
    Confidence Interval (2-Sided) 95%
    0.55 to 1.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1254
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.62
    Confidence Interval (2-Sided) 95%
    0.87 to 3.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6670
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.13
    Confidence Interval (2-Sided) 95%
    0.65 to 1.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0525
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Remission Rate
    Estimated Value 1.70
    Confidence Interval (2-Sided) 95%
    0.98 to 2.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Percentage of Participants With CGI-I Response From End of Phase A (Week 8 Visit).
    Description CGI-I response is defined as CGI-I of 1 [very much improved] or 2 [much improved].
    Time Frame Week 9, 10, 11, 12, 13 and 14.

    Outcome Measure Data

    Analysis Population Description
    ITT dataset consisted of all randomized participants who had an End of Phase A value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    Measure Participants 62 119 118 126
    Week 9 (N=62, 117, 116, 121)
    16.1
    26%
    11.1
    9.3%
    14.7
    12.1%
    14.9
    11.8%
    Week 10 (N=62, 119, 118, 126)
    25.8
    41.6%
    17.6
    14.7%
    24.6
    20.3%
    27.0
    21.4%
    Week 11 (N=62, 119, 118, 126)
    32.3
    52.1%
    29.4
    24.5%
    35.6
    29.4%
    29.4
    23.3%
    Week 12 (N=62, 119, 118, 126)
    35.5
    57.3%
    33.6
    28%
    42.4
    35%
    31.7
    25.2%
    Week 13 (N=62, 119, 118, 126)
    37.1
    59.8%
    37.0
    30.8%
    49.2
    40.7%
    33.3
    26.4%
    Week 14 (N=62, 119, 118, 126)
    38.7
    62.4%
    37.0
    30.8%
    52.5
    43.4%
    41.3
    32.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9462
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.52 to 1.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4971
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.80
    Confidence Interval (2-Sided) 95%
    0.43 to 1.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 9 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8118
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    0.53 to 1.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8323
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.59 to 1.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0930
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.68
    Confidence Interval (2-Sided) 95%
    0.43 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 10 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5530
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.88
    Confidence Interval (2-Sided) 95%
    0.59 to 1.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8007
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.69 to 1.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8945
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.03
    Confidence Interval (2-Sided) 95%
    0.71 to 1.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 11 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3837
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    0.83 to 1.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7064
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.09
    Confidence Interval (2-Sided) 95%
    0.72 to 1.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7469
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.06
    Confidence Interval (2-Sided) 95%
    0.74 to 1.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 12 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0832
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.34
    Confidence Interval (2-Sided) 95%
    0.97 to 1.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6611
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.09
    Confidence Interval (2-Sided) 95%
    0.74 to 1.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4435
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.13
    Confidence Interval (2-Sided) 95%
    0.83 to 1.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 13 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0118
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.47
    Confidence Interval (2-Sided) 95%
    1.09 to 1.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.15 mg Fixed Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5111
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Chi-squared, Corrected
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.89
    Confidence Interval (2-Sided) 95%
    0.63 to 1.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection OPC-34712 0.5 ± 0.25 mg Low Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4903
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 0.90
    Confidence Interval (2-Sided) 95%
    0.66 to 1.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection OPC-34712 1.5 ± 0.5 mg High Dose, Placebo
    Comments Week 14 values presented here.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0662
    Comments Cochran-Mantel-Haenszel general association test controlling for study center.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Ratio of Response Rate
    Estimated Value 1.28
    Confidence Interval (2-Sided) 95%
    0.98 to 1.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame From Randomization to 30 (+2) days after the end of Phase B (Week 14/End of treatment).
    Adverse Event Reporting Description The Safety Sample comprises those randomized participants in Phase B who received at least one dose of double-blind study medication as indicated on the dosing record.
    Arm/Group Title OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Arm/Group Description The participants received 0.15 mg/day OPC-34712 along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 0.50 mg OPC-34712, then 0.50 ± 0.25 mg/day along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received 1.5 mg OPC-34712, then 1.5 ± 0.50 mg/day along with the physician assigned ADT from Week 9 to Week 14/ Early Termination. The participants received double-blind placebo as an adjunctive therapy along with the physician assigned ADT from Week 9 to Week 14/ Early Termination.
    All Cause Mortality
    OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/62 (0%) 0/120 (0%) 2/121 (1.7%) 1/126 (0.8%)
    Injury, poisoning and procedural complications
    Radius fracture 0/62 (0%) 0/120 (0%) 1/121 (0.8%) 0/126 (0%)
    Ulna fracture 0/62 (0%) 0/120 (0%) 1/121 (0.8%) 0/126 (0%)
    Renal and urinary disorders
    Renal mass 0/62 (0%) 0/120 (0%) 0/121 (0%) 1/126 (0.8%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/62 (0%) 0/120 (0%) 1/121 (0.8%) 0/126 (0%)
    Other (Not Including Serious) Adverse Events
    OPC-34712 0.15 mg Fixed Dose OPC-34712 0.5 ± 0.25 mg Low Dose OPC-34712 1.5 ± 0.5 mg High Dose Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/62 (33.9%) 37/120 (30.8%) 47/121 (38.8%) 37/126 (29.4%)
    Gastrointestinal disorders
    Diarrhoea 1/62 (1.6%) 0/120 (0%) 10/121 (8.3%) 5/126 (4%)
    Nausea 0/62 (0%) 7/120 (5.8%) 2/121 (1.7%) 3/126 (2.4%)
    Infections and infestations
    Nasopharyngitis 3/62 (4.8%) 7/120 (5.8%) 5/121 (4.1%) 2/126 (1.6%)
    Upper respiratory tract infection 4/62 (6.5%) 10/120 (8.3%) 7/121 (5.8%) 6/126 (4.8%)
    Investigations
    Weight increased 3/62 (4.8%) 7/120 (5.8%) 9/121 (7.4%) 1/126 (0.8%)
    Nervous system disorders
    Akathisia 4/62 (6.5%) 6/120 (5%) 10/121 (8.3%) 4/126 (3.2%)
    Headache 5/62 (8.1%) 9/120 (7.5%) 6/121 (5%) 12/126 (9.5%)
    Psychiatric disorders
    Insomnia 5/62 (8.1%) 3/120 (2.5%) 4/121 (3.3%) 4/126 (3.2%)
    Restlessness 4/62 (6.5%) 1/120 (0.8%) 5/121 (4.1%) 6/126 (4.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Global Medical Affairs
    Organization Otsuka Pharmaceutical Development & Commercialization, Inc
    Phone 800 562-3974
    Email
    Responsible Party:
    Otsuka Pharmaceutical Development & Commercialization, Inc.
    ClinicalTrials.gov Identifier:
    NCT00797966
    Other Study ID Numbers:
    • 331-08-211
    First Posted:
    Nov 25, 2008
    Last Update Posted:
    Feb 29, 2016
    Last Verified:
    Feb 1, 2016