A Study of TD-9855 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)

A Phase 2 Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Proof-of-Concept Study of TD-9855 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)

The safety and efficacy of multiple dosages of TD-9855, administered once daily, will be evaluated in adult males with ADHD.

Study Overview

• Status: Completed
• Conditions: ADHD; Attention-Deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: Placebo; Drug: TD-9855

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Bradenton, Florida, United States, 34201
      • Florida Clinical Research Center, LLC
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc.
    • Maitland, Florida, United States, 34201
      • Florida Clinical Research Center
    • Palm Beach, Florida, United States, 33407
      • Janus Ctr. for Psychiatric Research
  • Georgia
    • Smyrna, Georgia, United States, 30080
      • Carman Research
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Midwest Research GRoup
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Ctr. for Psychiatry & Behavioral Med.
  • New York
    • New York, New York, United States, 10016
      • Adult ADHD Program
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Lincoln Research
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare of Memphis
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Clinical Trials
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research, LC
    • Salt Lake City, Utah, United States, 84105
      • Psychiatric & Behavioral Solutions
  • Washington
    • Seattle, Washington, United States, 98104
      • Summit Research Network (Seattle), LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must meet the following ADHD diagnostic and inclusion criteria:
• Subjects must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for current ADHD subtypes (ADHD combined type, ADHD predominately inattentive type, ADHD predominately hyperactive-impulsive type) as assessed by the clinical interview and confirmed by Adult Attention-Deficit/Hyperactivity Disorder Clinical Diagnostic Scale (ACDS V1.2).
• Subjects must have a total score of 24 or greater on the AISRS at both the Screening and Baseline Visits AND the Baseline Visit AISRS scores must not vary by more than 20% from Screening.
• Subjects are required to have CGI-S score ≥4 (moderate) at both the Screening and Baseline Visits. Subjects should have at least moderate severity for ADHD symptoms.
• For women of childbearing potential, documentation of a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 0. All female subjects of childbearing potential must be using a highly effective method of birth control during the study and for at least 1 month after completion of study drug dosing.
• A highly effective method of birth control is defined as one that results in a low failure rate (i.e., <1% per year) when used consistently and correctly, such as condom + diaphragm, condom + spermicide, diaphragm + spermicide, or intrauterine device [IUD] with documented failure rate of <1% per year, or oral/injectable/implanted hormonal contraceptives used in combination with a barrier method.
• Women are considered to be not of childbearing potential if they have had a total hysterectomy or bilateral tubal ligation (documentation for either must be provided before enrollment) or are at least 2 years postmenopausal. Female subjects cannot be breast-feeding.

Exclusion Criteria:

Any current psychiatric disorder other than ADHD as defined in DSM-IV-TR as assessed by Mini International Neuropsychiatric Interview (MINI). Subjects with dysthymia that does not require pharmacological treatment will not be excluded.

• MADRS total score >15.
• A diagnosis of ADHD NOS.
• Any diagnosis of lifetime bipolar disorder or psychotic disorder
• A current diagnosis of any severe comorbid Axis II disorder
• Any history of mental retardation, organic mental disorders due to general medical condition or pervasive developmental disorder as defined by DSM-IV-TR.-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Placebo	Drug: Placebo; Once daily
EXPERIMENTAL: TD-9855 Dose 1	Drug: TD-9855; Once daily
EXPERIMENTAL: TD-9855 Dose 2	Drug: TD-9855; Once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in AISRS Total Score at Day 42	The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. It is a clinician-administered scale that measures all 18 symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The total score ranges from 0 to 54 with a negative change from baseline indicating an improvement in severity/reduction in symptoms.	Baseline and Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in BDEFS-SF: Self Report Total Score at Day 42	The BDEFS-SF: Self-Report is an empirically based tool for evaluating dimensions of adult executive functioning in daily life. The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80 with a negative change from baseline indicating an improvement in functioning.	Baseline and Day 42
Change From Baseline in AISRS Inattentive Subscale at Day 42	The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS inattentive subscale that measures all 9 inattentive symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The AISRS inattentive subscale score ranges from 0 to 27 with a negative change from baseline indicating an improvement in severity/reduction in symptoms.	Baseline and Day 42
Change From Baseline in AISRS Hyperactive-impulsive Subscale at Day 42	The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS hyperactive-impulsive subscale measures all 9 hyperactive/impulsive symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The AISRS hyperactive-impulsive subscale score ranges from 0 to 27 with a negative change from baseline indicating an improvement in severity/reduction in symptoms.	Baseline and Day 42
Percentage of Participants With an AISRS Response at Day 42	The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS total scale measures all 18 symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The total score ranges from 0 to 54. A responder is defined as a participant with >=30% reduction from baseline in AISRS total score.	Day 42
Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Day 42	The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participants' illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 1=normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7,extremely ill. A negative change from baseline indicates a reduction in illness.	Baseline and Day 42
Change From Baseline in Adult ADHD Self-Report Scale (ASRS) Total Score at Day 42	The ASRS is a checklist consisting of the 18 Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV-TR) criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS total score ranges from 0-72 with a negative change from baseline indicating a reduction in frequency of symptoms.	Baseline and Day 42
Change From Baseline in ASRS Inattentive Subscale at Day 42	The ASRS inattentive subscale is a checklist consisting of 9 DSM-IV-TR inattentive criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS inattentive subscale score ranges from 0-36 with a negative change from baseline indicating a reduction in frequency of symptoms.	Baseline and Day 42
Change From Baseline in ASRS Hyperactive-impulsive Subscale at Day 42	The ASRS hyperactive-impulsive subscale is a checklist consisting of 9 DSM-IV-TR hyperactive/impulsive criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS hyperactive-impulsive subscale score ranges from 0-36 with a negative change from baseline indicating a reduction in frequency of symptoms.	Baseline and Day 42
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 42	MADRS is a 10-item investigator-rated scale that assesses the range of symptoms that are most frequently observed in patients with major depression. The 10 selected items are rated on a scale of 0 (no depression) to 6 (highest level of depression) with anchors at 2-point intervals. Total scores on the MADRS range from 0 to 60 with a negative change from baseline indicating an improvement in levels of depression.	Baseline and Day 42
Percentage of Participants With a Reliable Change on the BDEFS-SF at Day 42	The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80. A reliable change is defined as a decrease in total BDEFS-SF score of 12 or more relative to the baseline value.	Baseline and Day 42
Percentage of Participants With a Reliable Change and Normalized Score on the BDEFS-SF at Day 42	The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80. A reliable change is defined as a decrease in total BDEFS-SF score of 12 or more relative to the baseline value. Normalization is defined as a post-baseline BDEFS-SF total score <45.	Baseline and Day 42
Change From Baseline in BDEFS-SF Symptom Count at Day 42	The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. A negative change from baseline in symptom count indicates an improvement in functioning. Only symptoms rated as occurring often or very often on the BDEFS-SF are included in the symptom count. Mean change from baseline in symptom count is reported	Baseline and Day 42

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Publications and helpful links

General Publications

• Kanodia J, Lo A, Baldwin RM, Graham RA, Bourdet DL. Pharmacokinetics of Ampreloxetine, a Norepinephrine Reuptake Inhibitor, in Healthy Subjects and Adults with Attention-Deficit/Hyperactive Disorder or Fibromyalgia Pain. Clin Pharmacokinet. 2021 Jan;60(1):121-131. doi: 10.1007/s40262-020-00918-7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2011
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: October 20, 2011
• First Submitted That Met QC Criteria: October 21, 2011
• First Posted (ESTIMATE): October 24, 2011

Study Record Updates

• Last Update Posted (ACTUAL): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Attention-Deficit/Hyperactivity Disorder; Adult ADHD
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: 0085

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.