Study of the Safety and Efficacy of OPC-34712 as a Complementary Therapy in the Treatment of Adult Attention Deficit/Hyperactivity Disorder

NCT01074294 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 331-08-213
• Study Type: interventional
• Target: 740
• Locations: 1 country
• Sites: 35

Brief Summary

This study tests the effects of an investigational antipsychotic drug (called OPC-34712) in adults with attention deficit hyperactivity disorder (ADHD) when taken with an approved stimulant medication to explore a possible impact on sleep, quality of life and cognitive function.

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

Inattention; Hyperactivity; Impulsivity; Distractibility; Procrastination; Disorganized; ADHD

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline (End of Phase A) in the CAARS-O:SV ADHD Symptoms Total Score (18 Items) to End of Phase B

  The CAARS-O:SV is a 30 items scale with 3 subscales: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Inattentive Symptoms (9 items), DSM- IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The Mixed model repeated measures (MMRM) model was used for analysis.

  Baseline [end of Phase A (Week 5)] to Week 11

Secondary Outcomes (32)

• Change From Baseline (End of Phase A) in Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) Total Score to End of Phase B

  Baseline [end of Phase A (Week 5)] to Week 11

• Change From Baseline (End of Phase A) in Sleep Improvement Measured by Insomnia Severity Index (ISI) Total Score to End of Phase B

  Baseline [end of Phase A (Week 5)] to Week 11

• Change From Baseline (End of Phase A) in Sleep Improvement Measured by ISI for Item 2 Score (Difficulty Staying Asleep) to End of Phase B

  Baseline [end of Phase A (Week 5)] to Week 11

• Change From Baseline (End of Phase A) in the Spatial Working Memory (SWM) Between Errors 4-8 Boxes Test Score as Measured by Cambridge Neuropsychological Test Automated Battery (CANTAB) to End of Phase B

  Baseline [end of Phase A (Week 5)] to Week 11

• Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11

  Baseline [end of Phase A (Week 5)] to Weeks 6, 7, 8, 9 and 10

Study Arms (4)

Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant

EXPERIMENTAL

Participants received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for 5 weeks. Once assigned to a stimulant by the investigator, participants remained on the same stimulant for the duration of the trial. Participants who met eligibility criteria i.e., who received prior treatment for adult ADHD and treatment-naïve participants were included in this arm group. Participants with incomplete response at the end of Phase A (Week 5) entered Phase B and rest of the participants continued to Phase A+.

Drug: Placebo; Drug: Stimulant Therapy

Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant

EXPERIMENTAL

Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV { Conners' Adult ADHD Rating Scale-Observer: Screening Version}, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a clinical global impression - improvement scale (CGI-I) score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 milligram (mg) tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).

Drug: OPDC-34712; Drug: Stimulant Therapy

Phase B (Double-blind Randomization Phase): Placebo + Stimulant

PLACEBO COMPARATOR

Participants with incomplete response (with a \> 0% and \< 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).

Drug: Placebo; Drug: Stimulant Therapy

Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant

EXPERIMENTAL

Participants with response (with a ≥ 30% reduction in ADHD Symptoms Total Score {18 items} between Baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV, or a CAARS-O:SV ADHD Symptoms Total Score {18 items} of \< 24 at Week 5, or a CGI-I score of \< 3 at Week 5) and non-response (with deterioration or no change in ADHD symptoms at Week 5) at the end of Phase A (Week 5), received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for an additional 6 weeks (up to Week 11).

Drug: Placebo; Drug: Stimulant Therapy

Interventions

OPDC-34712 DRUG

OPDC-34712 tablets, daily, Orally.

Also known as: Brexpiprazole

Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant

Placebo DRUG

Matching-placebo tablets, daily, Orally.

Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant; Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant; Phase B (Double-blind Randomization Phase): Placebo + Stimulant

Stimulant Therapy DRUG

Mixed amphetamine salts or Dexmethylphenidate hydrochloride (HCL) or Methylphenidate HCl or Lisdexamfetamine dimesylate as per standard of care.

Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant; Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant; Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant; Phase B (Double-blind Randomization Phase): Placebo + Stimulant

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female outpatients 18 to 55 years of age, inclusive, at the time of informed consent.
• Participants with a primary diagnostic and statistical manual of mental disorders, fourth edition, text revision (DSM-IV-TR) diagnosis of ADHD (including inattentive, hyperactive, and combined subtypes) as confirmed by the Conners' Adult ADHD diagnostic interview (CAADID). Participants may have received prior treatment for adult ADHD, may be currently receiving treatment for adult ADHD at screening, or may be treatment-naive.
• Participants willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and during the study period.

You may not qualify if:

• Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug.
• Participants with an adequate response, as determined by the investigator, to any stimulant taken for the treatment of adult ADHD after 18 years of age.
• Participants with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder.
• Participants who participated in a clinical trial within the last 180 days or who participated in more than two clinical trials within the past year.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (35)

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Little Rock, Arkansas, United States

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Beverly Hills, California, United States

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Irvine, California, 92612, United States

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Pasadena, California, United States

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San Francisco, California, United States

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Bradenton, Florida, United States

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Jacksonville, Florida, United States

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Maitland, Florida, United States

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North Miami, Florida, United States

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Orlando, Florida, United States

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South Miami, Florida, 33173, United States

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Atlanta, Georgia, United States

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Smyrna, Georgia, United States

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Indianapolis, Indiana, United States

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Overland Park, Kansas, United States

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Rochester Hills, Michigan, United States

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Saint Charles, Missouri, United States

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Cherry Hill, New Jersey, United States

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Willingboro, New Jersey, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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Dayton, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Woodstock, Vermont, United States

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Herndon, Virginia, United States

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Bellevue, Washington, United States

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Seattle, Washington, United States

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MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Spasm; Impulsive Behavior

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.

clinicaltransparency@otsuka-us.com

1-609-524-6788

Study Officials

• Study Director

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2010
• First Posted: February 24, 2010
• Study Start: March 16, 2010
• Primary Completion: June 20, 2011
• Study Completion: June 20, 2011
• Last Updated: February 2, 2023
• Results First Posted: February 2, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

US (35)