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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
134
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.
Placebo will be provided as white, opaque gelatin capsules in sham strengths of 1mg, 5mg, and 25mg
Florida Clinical Research Center, LLC
Bradenton, Florida, United States
Clinical Neuroscience Solutions, Inc.
Jacksonville, Florida, United States
Fidelity Clinical Research, Inc
Lauderhill, Florida, United States
Florida Clinical Research Center, LLC
Maitland, Florida, United States
Scientifc Clinical Research, Inc.
North Miami, Florida, United States
Clinical Neuroscience Solutions, Inc.
Orlando, Florida, United States
Atlanta Center For Clinical Research
Atlanta, Georgia, United States
CRI Worldwide, LLC (Lourdes Division)
Willingboro, New Jersey, United States
Neuro-Behavioral Clinical Research, Inc.
Canton, Ohio, United States
Midwest Clinical Research Center
Dayton, Ohio, United States
...and 6 more locations
CAARS-INV ADHD-rating scale
•Clinician-administered ADHD-rating scale (CAARS-INV) and is the total of 3 subscales: Inattention, Hyperactivity-Impulsivity, and ADHD Index \[ Time Frame: Week -3, Day 1, Week 1, Week 4 (evaluation of 1mg dose); Week 8 (evaluation of 5mg Dose); and Week 12 (evaluation of 25mg dose)\]
Time frame: Week 12
CAARS-INV subscales
CAARS-INV subscales: Inattention, Hyperactivity-Impulsivity, and ADHD Index, obtained \[Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)\]
Time frame: Week 12
CogState ADHD Battery
CogState ADHD test battery \[Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)\]
Time frame: Week 12
CogState Stop-Signal Task scores
CogState Stop-Signal Task scores \[Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)\]
Time frame: Week 12
CAARS-Self Rating (CAARS-S) total score
CAARS-S total score \[Time frame: Week -3, Day 1, Week 1, Week 4, Week 8, Week 12,Early Withdrawal (EW)\]
Time frame: Week 12
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