Study of the Safety and Efficacy of Fixed Dose OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Pyxis Trial) (Pyxis)

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of the Safety and Efficacy of Fixed Dose OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Pyxis Trial

To compare the effect of OPC-34712 (brexpiprazole) to the effect of placebo (an inactive substance) as add on treatment to an assigned FDA approved antidepressant treatment (ADT) in patients with Major Depressive Disorder who demonstrate an incomplete response to a prospective trial of the same assigned FDA approved ADT

Study Overview

• Status: Completed
• Conditions: Mental Disorders; Depressive Disorder; Depression; Mood Disorders; Depressive Disorder, Major
• Intervention / Treatment: Drug: OPC-34712 + ADT; Drug: Placebo + ADT

• Study Type: Interventional
• Enrollment (Actual): 826
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Penticton, British Columbia, Canada
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada
      • Research Site
  • Quebec
    • Gatineau, Quebec, Canada
      • Research Site
• France
  • Arcachon, France
    • Research Site
  • Elancourt, France
    • Research Site
  • Orvault, France
    • Research Site
  • Palaiseau, France
    • Research Site
  • Toulouse, France
    • Research Site
• Poland
  • Belchatow, Poland
    • Research Site
  • Gdynia, Poland
    • Research Site
  • Kielce, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Tuszyn, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
  • Upper Silesia
    • Katowice, Upper Silesia, Poland
      • Research Site
  • Woj. Wielkopolskie
    • Poznan, Woj. Wielkopolskie, Poland
      • Research Site
• Slovakia
  • Bratislava, Slovakia
    • Research Site
  • Kosice-Barca, Slovakia
    • Research Site
  • Levice, Slovakia
    • Research Site
  • Michalovce, Slovakia
    • Research Site
• United States
  • California
    • Arcadia, California, United States
      • Research Site
    • Beverly Hills, California, United States
      • Research Site
    • Fresno, California, United States
      • Research Site
    • Oceanside, California, United States
      • Research Site
    • San Diego, California, United States
      • Research Site
    • San Francisco, California, United States
      • Research Site
    • Sherman Oaks, California, United States
      • Research Site
  • Colorado
    • Denver, Colorado, United States
      • Research Site
  • Connecticut
    • Norwalk, Connecticut, United States
      • Research Site
  • Florida
    • Coral Springs, Florida, United States
      • Research Site
    • Fort Myers, Florida, United States
      • Research Site
    • Hialeah, Florida, United States
      • Research Site
    • Jacksonville, Florida, United States
      • Research Site
    • Melbourne, Florida, United States
      • Research Site
    • Orlando, Florida, United States
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States
      • Research Site
  • Kansas
    • Prairie Village, Kansas, United States
      • Research Site
    • Wichita, Kansas, United States
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States
      • Research Site
    • Shreveport, Louisiana, United States
      • Research Site
  • Massachusetts
    • Belmont, Massachusetts, United States
      • Research Site
    • Boston, Massachusetts, United States
      • Research Site
  • Nebraska
    • Lincoln, Nebraska, United States
      • Research Site
  • New York
    • New York, New York, United States
      • Research Site
    • Rochester, New York, United States
      • Research Site
  • Ohio
    • Dayton, Ohio, United States
      • Research Site
    • Toledo, Ohio, United States
      • Research Site
  • Oregon
    • Salem, Oregon, United States
      • Research Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States
      • Research Site
    • Bala Cynwyd, Pennsylvania, United States
      • Research Site
    • Bridgeville, Pennsylvania, United States
      • Research Site
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • Texas
    • San Antonio, Texas, United States
      • Research Site
  • Utah
    • Murray, Utah, United States
      • Research Site
  • Vermont
    • Woodstock, Vermont, United States
      • Research Site
  • Virginia
    • Richmond, Virginia, United States
      • Research Site
  • Washington
    • Seattle, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase B; Drug: OPC-34712 + ADT Drug: Placebo + ADT	Drug: OPC-34712 + ADT; Tablet, Oral, 2 mg OPC-34712 and FDA Approved Antidepressant Therapy (ADT); Drug: Placebo + ADT; Placebo + FDA Approved Antidepressant (ADT)
Placebo Comparator: Phase A; Intervention: Drug: Placebo + ADT	Drug: Placebo + ADT; Placebo + FDA Approved Antidepressant (ADT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score for the Efficacy Sample.	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 will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.	Baseline and Week 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score for the Efficacy Sample Per the Final Protocol.	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 will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.	Baseline and Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in Sheehan Disability Scale (SDS) Score for the Efficacy Sample.	The SDS is a self-rated instrument used to measure the effect of the patient'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 patient 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.	Baseline and Week 14
Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in SDS Score for the Efficacy Sample Per the Final Protocol	The SDS is a self-rated instrument used to measure the effect of the patient'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 patient 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.	Baseline and Week 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample.	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 will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.	Week 9, 10, 11, 12, and 13
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol.	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 will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.	Week 9, 10, 11, 12, and 13
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample.	The items on CGI-I scale 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. The CGI-I was measured in related to Baseline (Week 8).	Week 9, 10, 11, 12, 13, and 14
Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol.	The items on CGI-I scale 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. The CGI-I was measured in related to Baseline (Week 8).	Week 9, 10, 11, 12, 13, and 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample.	Items on CGI-S scale 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) will be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7.	Week 9, 10, 11, 12, 13, and 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol.	Items on CGI-S scale 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) will be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7.	Week 9, 10, 11, 12, 13, and 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample.	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. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. Should items 11 and 12 be rated both, then the maximum of the two scores will be used. The same approach will be used for handling items 13 and 14. 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.	Week 9, 10, 11, 12, 13, and 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol.	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. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. Should items 11 and 12 be rated both, then the maximum of the two scores will be used. The same approach will be used for handling items 13 and 14. 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.	Week 9, 10, 11, 12, 13, and 14
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample.	The SDS is a self-rated instrument used to measure the effect of the patient'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 patient 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.	Week 11 and 14
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol.	The SDS is a self-rated instrument used to measure the effect of the patient'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 patient 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.	Week 11 and 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Depression (HAM-D) Rating Scale Total Score for the Efficacy Sample.	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 sum of the scores from the first 17 items; 0-7 =Normal; 8-13 =mild depression; 14-18 =moderate depression; 19-22 =severe depression; ≥23 =very severe depression. The total score ranges from 0 to 52, with higher score indicating worse depressive symptoms.	Baseline and Week 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-D Rating Scale Total Score for the Efficacy Sample Per the Final Protocol.	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 sum of the scores from the first 17 items; 0-7 =Normal; 8-13 =mild depression; 14-18 =moderate depression; 19-22 =severe depression; ≥23 =very severe depression. The total score ranges from 0 to 52, with higher score indicating worse depressive symptoms.	Baseline and Week 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Anxiety (HAM-A) Rating Scale Total Score for the Efficacy Sample	The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the "best" rating and 4 is the "worst" rating. If no item scores are missing, then the HAM-A total score is the sum of all 14 item scores. The possible total scores are from 0 to 56, with higher scores indicating worse anxiety symptoms.	Baseline and Week 14
Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-A Rating Scale Total Score for the Efficacy Sample Per the Final Protocol.	The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the "best" rating and 4 is the "worst" rating. If no item scores are missing, then the HAM-A total score is the sum of all 14 item scores. The possible total scores are from 0 to 56, with higher scores indicating worse anxiety symptoms.	Baseline and Week 14
Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.	The MADRS response was defined as >/=50% reduction in MADRS total score from end of Phase A (Week 8).	Baseline and Week 14
Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.	The MADRS response was defined as >/=50% reduction in MADRS total score from end of Phase A (Week 8).	Baseline and Week 14
Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.	MADRS remission was defined as </=10 and >/=50% reduction in MADRS total score from end of Phase A (Week 8).	Baseline and Week 14
Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.	MADRS remission was defined as </=10 and >/=50% reduction in MADRS total score from end of Phase A (Week 8).	Baseline and Week 14
Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.	CGI-I response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).	Baseline and Week 14
Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.	CGI-I response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).	Baseline and Week 14

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Newcomer JW, Eriksson H, Zhang P, Meehan SR, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Major Depressive Disorder Treated With Adjunctive Brexpiprazole: Pooled Analysis of Phase 3 Clinical Studies. J Clin Psychiatry. 2019 Oct 1;80(6):18m12680. doi: 10.4088/JCP.18m12680.
• Hobart M, Zhang P, Weiss C, Meehan SR, Eriksson H. Adjunctive Brexpiprazole and Functioning in Major Depressive Disorder: A Pooled Analysis of Six Randomized Studies Using the Sheehan Disability Scale. Int J Neuropsychopharmacol. 2019 Mar 1;22(3):173-179. doi: 10.1093/ijnp/pyy095.
• McIntyre RS, Weiller E, Zhang P, Weiss C. Brexpiprazole as adjunctive treatment of major depressive disorder with anxious distress: Results from a post-hoc analysis of two randomised controlled trials. J Affect Disord. 2016 Sep 1;201:116-23. doi: 10.1016/j.jad.2016.05.013. Epub 2016 May 12.
• Thase ME, Youakim JM, Skuban A, Hobart M, Augustine C, Zhang P, McQuade RD, Carson WH, Nyilas M, Sanchez R, Eriksson H. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants. J Clin Psychiatry. 2015 Sep;76(9):1224-31. doi: 10.4088/JCP.14m09688.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: May 24, 2011
• First Submitted That Met QC Criteria: May 24, 2011
• First Posted (Estimate): May 25, 2011

Study Record Updates

• Last Update Posted (Estimate): November 26, 2015
• Last Update Submitted That Met QC Criteria: October 26, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; OPC-34712; brexpiprazole; Adjunctive Treatment
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Depression; Depressive Disorder; Disease; Mental Disorders; Mood Disorders; Depressive Disorder, Major
• Other Study ID Numbers: 331-10-228