A Trial Evaluating the Long-term Safety and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder

Phase 3

Completed

Conditions: Attention Deficit Disorder
Attention Deficit Hyperactivity Disorder

Interventions: Drug: Centanafadine SR

Registration Number: NCT03605849

Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary: This study evaluated the long-term safety and tolerability of centanafadine sustained-release (SR) tablets, administered twice daily (BID) in the treatment of adults with attention deficit hyperactivity disorder (ADHD).

Detailed Description: This open-label study assessed the overall safety and tolerability of 400 mg total daily dose centanafadine SR tablets in participants, over the course of approximately 52 weeks. This study has accepted rollover participants from both the 405-201-00013 and 405-201-00014 trials. For individuals that did not participate in one of the studies mentioned above, they will be able to enroll if they meet the inclusion criteria as outlined below.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 662

Inclusion Criteria

De novo participants must meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for ADHD (including predominantly inattentive presentation, hyperactive presentation, or combined presentation) as confirmed by the Adult ADHD Clinical Diagnostic Scale (ACDS) Version 1.2. To confirm that ADHD is the primary diagnosis, the Mini International Neuropsychiatric Interview (MINI) will be used to identify and exclude other psychiatric conditions which would preclude enrollment.
Participants are 18 to 55 years of age, inclusive, at the time of consent.
Participants have BMI of 18 to 40, inclusive
Participants are willing to discontinue all prohibited psychotropic medications starting from the time of signing the informed consent and up to the 10-day safety follow-up period.

Exclusion Criteria

Participants has a DSM-5 diagnosis of Other Specified or Unspecified Attention-Deficit/Hyperactivity Disorder as confirmed by ACDS Version 1.2.
Participant has a current comorbid psychiatric disorder that is either controlled with medications prohibited in this trial or is uncontrolled and associated with significant symptoms, including but not limited to: a current major depressive episode (per DSM-5 criteria), current symptoms (past 90 days) meeting the DSM-5 criteria for a diagnosis of generalized anxiety disorder, obsessive compulsive disorder, panic disorder, or posttraumatic stress disorder, as established by the MINI. NOTE: Participants with mild mood or anxiety symptoms that do not meet criteria for diagnosis, who do not require treatment based on the Investigator's assessment, and do not confound efficacy or safety assessments in the opinion of the examining Investigator, may be included.
Participants that have a positive alcohol test (via breathalyzer or blood), a positive drug screen for cocaine, or other illicit drugs (excluding marijuana). Participants with a positive drug screen for confirmed prescription medications at baseline will not be permitted to continue participation in Trial 405-201-00015. NOTE: Participants that tested positive for marijuana may be permitted to be enrolled if they have no evidence of a substance use disorder, and if they agree to refrain from use for the duration of the trial. Allowance for participants testing positive for marijuana at screening require explicit approval from the medical monitor.

Rollover Participants: Rollover Enrollment has ended 28Aug2020.

Inclusion Criteria:

Participants who completed the double-blind treatment period and 7-day follow-up after last dose of investigational medicinal product (IMP) in double-blind trials and who, in the opinion of the investigator, could potentially benefit from centanafadine for ADHD.

Exclusion Criteria:

Participants who, during the double-blind phase 3 trial experienced, in the opinion of the investigator, poor tolerability to trial medication or whose safety assessments resulted in new concerns that would suggest the participant may not be appropriate for a 52-week treatment with trial medication.
Participants who have re-initiated any therapy for adult ADHD during the 7-day follow-up period after the final treatment visit of the double-blind phase 3 trial.
Participants that have a positive alcohol test (via breathalyzer or blood), a positive drug screen for cocaine, or other illicit drugs (excluding marijuana). Participants with a positive drug screen for confirmed prescription medications at baseline will not be permitted to continue participation in Trial 405-201-00015. NOTE: Participants that test positive for marijuana may not be permitted to rollover into the open label study, and must agree to refrain from use for the duration of the open label trial. Allowance for participants testing positive for marijuana at time of rollover requires explicit approval from the medical monitor.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Centanafadine	Centanafadine SR	400 mg total daily dose

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Graded by Severity	From first dose of study drug up to 30 days after last dose of study drug (Up to approximately Week 56)	An AE is defined as any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with an onset date on or after the first dose of IMP. They are all adverse events that started after the start of centanafadine; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption or reduction of study therapy. TEAEs were graded on a 3-point scale and the intensity of an adverse experience was defined as follows: 1 = Mild: Discomfort noticed, but no disruption to daily activity, 2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity, and 3 = Severe: Inability to work or perform normal daily activity.

Secondary Outcome Measures