Efficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Targacept Inc.
ClinicalTrials.gov Identifier:
NCT01124708
First received: May 5, 2010
Last updated: September 3, 2013
Last verified: October 2011
  Purpose

ADHD has been associated with persistent deficits in the efficient allocation of attention and supports the notion that regulation of the cholinergic system may improve these cognitive deficits in ADHD. It has been suggested that the effects of nicotine are most pronounced on tasks that demand effortful processing (Rusted and Warburton 1994). In addition, a recent theory proposes that the cholinergic system allocates additional attentional resources during tasks that are demanding (i.e. sustained attention, set shifting, etc; Sarter and Bruno 1997). Thus it may be that in ADHD, cholinergic systems are under-responsive or under-developed and thus stimulation of nicotinic receptors via nicotinic agents may result in improved cognitive performance particularly on tests requiring effortful processing.


Condition Intervention Phase
ADHD
Drug: TC-5619-238
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter, Fixed Dose Titration Study to Assess Efficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)

Resource links provided by NLM:


Further study details as provided by Targacept Inc.:

Primary Outcome Measures:
  • CAARS-INV ADHD-rating scale [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    •Clinician-administered ADHD-rating scale (CAARS-INV) and is the total of 3 subscales: Inattention, Hyperactivity-Impulsivity, and ADHD Index [ Time Frame: Week -3, Day 1, Week 1, Week 4 (evaluation of 1mg dose); Week 8 (evaluation of 5mg Dose); and Week 12 (evaluation of 25mg dose)]


Secondary Outcome Measures:
  • CAARS-INV subscales [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    CAARS-INV subscales: Inattention, Hyperactivity-Impulsivity, and ADHD Index, obtained [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]

  • CogState ADHD Battery [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    CogState ADHD test battery [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]

  • CogState Stop-Signal Task scores [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    CogState Stop-Signal Task scores [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]

  • CAARS-Self Rating (CAARS-S) total score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    CAARS-S total score [Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)]


Enrollment: 134
Study Start Date: May 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg
Drug: Placebo
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg
Active Comparator: TC-5619
TC-5619-238 will be provided as white, opaque gelatin capsules in strengths of 1mg, 5mg, and 25mg (as free base). Subjects will take 1mg TC-5619, 5mg TC-5619, 25mg TC-5619, one capsule once daily p.o.
Drug: TC-5619-238
TC-5619-238 will be provided as white, opaque gelatin capsules in strengths of 1mg, 5mg, and 25mg (as free base). Subjects will take 1mg TC-5619, 5mg TC-5619, 25mg TC-5619, or matching placebo - one capsule once daily p.o.

Detailed Description:

A randomized, parallel, forced-titration design is being used to assess effects of TC-5619 versus placebo on efficacy. A parallel group design allows the effects of TC-5619 to be clearly established, and the randomized nature of the design allows minimization of observer and subject bias. Because a forced dose up-titration design will be used, effects of individual doses will be preliminary, because the design confounds dose with time.

The doses chosen (1mg, 5mg, and 25mg) reflect an appropriate range around the anticipated efficacious dose (3-10 mg), based upon preclinical extrapolations to the human, and upon the pro-cognitive effects of TC-5619 identified by CDR in the MRD study (Targacept Study TC-5619-238-CLP-002).

All subjects will be tobacco non-users. It is possible that tobacco (nicotine) interferes with α7 NNR-mediated effects.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Diagnosis of ADHD per DSM-IV TR criteria
  2. Score > 2 on at least 6 of 9 items in at least 1 subscale of the CAARS-INV
  3. Score > 4 (at least moderate) on the Clinical Global Impression-Severity (CGI-S) index
  4. Age 18 - 65, male or female
  5. Tobacco non-users as indicated by lack of tobacco use within the last year prior to Screening, and by negative urinary cotinine level of < 50ng/mL after quantification
  6. Able to understand and sign informed consent

Exclusion Criteria:

  1. Current DSM-IV Axis I psychiatric disorder other than ADHD; use of MINI to exclude other major DSM-IV TR psychiatric diagnoses
  2. Known or suspected drug abuse within the last 12 months prior to Screening
  3. Urine drug screen positive for illegal or non-prescribed drugs at Screening
  4. Patients at imminent risk of suicide or of danger to themselves or others
  5. Use of drugs affecting cognitive function within 3 weeks prior to Day 1, including use of any medications for treatment of ADHD. Any medication wash-outs must be completed during the 3 weeks between Screening and Day 1.
  6. Any other restricted or prohibited drugs.
  7. Other concomitant medications that have been changed within 4 weeks prior to Screening
  8. Unable to comply with study procedures in opinion of investigator, including CogState ADHD test battery
  9. History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, CV, GI, or urological disorder; or diagnosis of major depressive disorder
  10. Myocardial infarction within past year
  11. Seizure disorder within past year
  12. Type 1 diabetes mellitus (DM); type 2 DM that requires medication (diet-controlled allowed)
  13. HbA1C > 7.4 at Screening
  14. BMI < 15 or > 35; male weight < 100 lbs; female weight < 80 lbs.
  15. Current TB or known systemic infection (HBV, HCV, HIV)
  16. Clinically significant finding on physical exam
  17. Clinically significant lab or ECG abnormality that could be a safety issue in the study, including QTcF > 450 (males) or QTcF > 480msec (females), and excluding LFTs > 1.5 times upper limits of normal
  18. Women of child-bearing potential and men unwilling or unable to use accepted methods of birth control
  19. Women with a positive pregnancy test, or who are lactating
  20. Participation in another clinical trial in last 3 months prior to Screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01124708

Locations
United States, Florida
Florida Clinical Research Center, LLC
Bradenton, Florida, United States, 34208
Clinical Neuroscience Solutions, Inc.
Jacksonville, Florida, United States, 32216
Fidelity Clinical Research, Inc
Lauderhill, Florida, United States, 33319
Florida Clinical Research Center, LLC
Maitland, Florida, United States, 32751
Scientifc Clinical Research, Inc.
North Miami, Florida, United States, 33161
Clinical Neuroscience Solutions, Inc.
Orlando, Florida, United States, 32806
United States, Georgia
Atlanta Center For Clinical Research
Atlanta, Georgia, United States, 30308
United States, New Jersey
CRI Worldwide, LLC (Lourdes Division)
Willingboro, New Jersey, United States, 08046
United States, Ohio
Neuro-Behavioral Clinical Research, Inc.
Canton, Ohio, United States, 44718
Midwest Clinical Research Center
Dayton, Ohio, United States, 45417
United States, Oregon
Oregon Center For Clinical Investigations, Inc. (OBBI, Inc.)
Portland, Oregon, United States, 97210
United States, Pennsylvania
CRI Worldwide, LLC (Kirkbride Division)
Philadelphia, Pennsylvania, United States, 19139
United States, Tennessee
Clinical Neuroscience Solutions, Inc.
Memphis, Tennessee, United States, 38119
United States, Texas
FutureSearch Clinical Trials, LP
Austin, Texas, United States, 78756
Claghorn-Lessem Research Clinic
Houston, Texas, United States, 77008
United States, Vermont
Fletch Allen Health Care, Dept. of Psychiatry, Univ. of Vermont
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Targacept Inc.
Investigators
Principal Investigator: Paul Newhouse, MD Fletcher Allen Health Care, Dept. of Psychiatry
  More Information

No publications provided

Responsible Party: Targacept Inc.
ClinicalTrials.gov Identifier: NCT01124708     History of Changes
Other Study ID Numbers: TC-5619-238-CRD-002, PRO-05619-CRD-002
Study First Received: May 5, 2010
Last Updated: September 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Targacept Inc.:
ADHD
Attention Deficit Hyperactive Disorder

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Dyskinesias
Mental Disorders
Mental Disorders Diagnosed in Childhood
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on October 21, 2014