Safety and Efficacy Study of Centanafadine Sustained-Release (CTN SR) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

NCT02547428 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NVI-EB-1020-202
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 4

Brief Summary

This was a Phase 2b, randomized, double-blind, multicenter, 2-period, 2-treatment, crossover study to evaluate safety and efficacy of CTN SR compared with placebo in adults with ADHD. Efficacy was also evaluated in the subgroup of adults with ADHD treated with a target CTN SR dose of 400 mg/day.

Conditions

Attention Deficit Disorder With Hyperactivity

Keywords

centanafadine sustained-release; Attention-Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Total Attention-Deficit Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV) Score

  The ADHD-RS-IV consists of 18 items and is designed to reflect the participant's current ADHD symptomatology; the severity, frequency, and impairment are measured for each of the items. The 18 items are grouped into 2 subscales of 9 symptoms each: Hyperactivity/Impulsivity (even numbered items 2-18) and Inattentiveness (odd numbered items 1-17). Each item is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), with the total score for the rating scale ranging from 0 to 54. Higher scores indicate more severe disease. A negative change from Baseline indicates improvement.

  Baseline and Week 3

• Change From Baseline in ADHD-RS-IV Score for Subgroup of Participants With Target CTN SR Dose of 400 mg/Day

  The ADHD-RS-IV consists of 18 items and is designed to reflect the participant's current ADHD symptomatology; the severity, frequency, and impairment are measured for each of the items. The 18 items are grouped into 2 subscales of 9 symptoms each: Hyperactivity/Impulsivity (even numbered items 2-18) and Inattentiveness (odd numbered items 1-17). Each item is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), with the total score for the rating scale ranging from 0 to 54. Higher scores indicate more severe disease. A negative change from Baseline indicates improvement.

  Baseline and Week 3

Secondary Outcomes (20)

• Change From Baseline in ADHD-RS-IV Score Total Score After 1 and 2 Weeks of Double-blind Treatment

  Baseline, Weeks 1, and 2

• Change From Baseline in ADHD-RS-IV Score Total Score After 1 and 2 Weeks of Double-blind Treatment for Subgroup of Participants With Target CTN SR Dose of 400 mg/Day

  Baseline, Weeks 1, and 2

• Change From Baseline in ADHD-RS-IV Inattention Subscale Score of Double-blind Treatment

  Baseline, Weeks 1, 2 and 3

• Change From Baseline in ADHD-RS-IV Inattention Subscale Score of Double-blind Treatment for Subgroup of Participants With Target CTN SR Dose of 400 mg/Day

  Baseline, Weeks 1, 2 and 3

• Change From Baseline in ADHD-RS-IV Hyperactivity/Impulsivity Subscale Score of Double-blind Treatment

  Baseline, Weeks 1, 2 and 3

Study Arms (2)

CTN SR First, Then Placebo

EXPERIMENTAL

Participants received CTN SR tablets starting at a dose of 100 or 200 milligrams (mg) on Day 1. Dose was up titrated up to 800 mg daily dose for up to 3 weeks in Period 1. The dose was decreased based on safety and tolerability based on Investigator's discretion, followed by a washout Period of 1 week followed by matching-placebo for up to 3 weeks in Period 2. The most common total daily dose (TDD) was 400 mg/day.

Drug: CTN SR; Drug: Matching placebo

Placebo First, Then CTN SR

EXPERIMENTAL

Participants received matching-placebo for up to 3 weeks in Period 1, followed by a washout Period of 1 week, followed by CTN SR tablets starting at a dose of 100 or 200 mg on Day 1. Dose was up titrated up to 800 mg daily dose for up to 3 weeks in Period 2. The dose was decreased based on safety and tolerability based on Investigator's discretion. The most common TDD was 400 mg/day.

Drug: CTN SR; Drug: Matching placebo

Interventions

CTN SR DRUG

CTN SR tablets, daily, Orally.

Also known as: Centanafadine Sustained-Release

CTN SR First, Then Placebo; Placebo First, Then CTN SR

Matching placebo DRUG

Matching-placebo tablets daily, orally.

CTN SR First, Then Placebo; Placebo First, Then CTN SR

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participant was 18 to 60 years of age, inclusive, at the time of consent.
• Participant meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD, defined as, established by a comprehensive psychiatric evaluation based on DSM-5 criteria with at least 5 of the 9 subtype criteria met, as determined by the Conners' Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-4). Note: DSM-5 was used for screening / diagnosis and DSM-4 was used for evaluation throughout the study.
• Participant had a Baseline score of greater than or equal to 28 using the Attention-Deficit Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV).
• Participant had a minimum score of 4 on the Clinical Global Impression of Severity at Baseline.
• Participant was functioning at an age-appropriate level intellectually, as judged by the Investigator.

You may not qualify if:

• Participants who were currently considered a suicide risk, any participant who had previously made a suicide attempt, or those who were currently demonstrating active suicidal ideation as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening, or if in the opinion of the investigator the participant was considered a suicide risk. Participants who developed suicidal ideation or behavior during the study as measured by the C-SSRS were discontinued and followed appropriately.
• The participant had a body mass index of less than 18.5 or greater than or equal to 40 at Baseline.
• Participant had a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might have confounded the results of safety assessments administered in the study or that might have increased risk to the participant.
• Participant had a history of seizures (other than infantile febrile seizures), any tic disorder (except transient tic disorder and participant had no episodes greater than or equal to 1 year), or a current diagnosis and/or a known family history of Tourette's Disorder (that is, first degree relatives).
• Participant had a known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke or other serious cardiac problems that may have placed them at increased vulnerability to potential sympathomimetic effects.
• Participant had a known family history of sudden cardiac death or ventricular arrhythmia.
• Participant had a history of significant bleeding or coagulation disorder and/or low platelet levels (less than 130 x 10\^9/liter) or increased international normalized ratio (greater than 1.3) at Screening.
• Participant had a history of cancer (other than noncomplicated basal or squamous cell cancer).
• Participant had any clinically significant 12-lead electrocardiogram or clinically significant laboratory abnormality at Screening and/or Baseline.
• Participant had current abnormal thyroid function, as defined as abnormal Screening thyroid stimulating hormone (less than 0.34 or greater than 5.6 micro-International Units/milliliter). Treatment with a stable dose of thyroid medication for at least 3 months was permitted.
• Participant had a resting sitting systolic blood pressure (SBP) greater than or equal to 140 millimeters of mercury (mm Hg) or diastolic blood pressure (DBP) greater than or equal to 90 mm Hg. No more than 1 repeat measurement was permitted.
• Participant had a history of hyponatremia.
• Participant was on an antihypertensive medication of any kind.
• Participant has a known history of orthostatic hypotension or has an orthostatic blood pressure drop of greater than or equal to 20 mm Hg (based on the drop between sitting and standing \[3 minutes\] SBP) at Screening or Baseline.
• Participant had a known history of hypertension.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (4)

Unknown Facility

Newport Beach, California, 92660, United States

Location

Unknown Facility

Bradenton, Florida, 34201, United States

Location

Unknown Facility

Maitland, Florida, 32751, United States

Location

Unknown Facility

Las Vegas, Nevada, 89128, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

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

clinicaltransparency@otsuka-us.com

+1-609-524-6788

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: September 11, 2015
• Study Start: August 3, 2015
• Primary Completion: June 4, 2016
• Study Completion: June 4, 2016
• Last Updated: November 11, 2021
• Results First Posted: November 11, 2021

Record last verified: 2021-10

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 (4)