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

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.

Inclusion criteria

• Diagnosis of ADHD per DSM-IV TR criteria
• Score > 2 on at least 6 of 9 items in at least 1 subscale of the CAARS-INV
• Score > 4 (at least moderate) on the Clinical Global Impression-Severity (CGI-S) index
• Age 18 - 65, male or female
• 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
• Able to understand and sign informed consent

Exclusion criteria

• Current DSM-IV Axis I psychiatric disorder other than ADHD; use of MINI to exclude other major DSM-IV TR psychiatric diagnoses
• Known or suspected drug abuse within the last 12 months prior to Screening
• Urine drug screen positive for illegal or non-prescribed drugs at Screening
• Patients at imminent risk of suicide or of danger to themselves or others
• 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.
• Any other restricted or prohibited drugs.
• Other concomitant medications that have been changed within 4 weeks prior to Screening
• Unable to comply with study procedures in opinion of investigator, including CogState ADHD test battery
• History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, CV, GI, or urological disorder; or diagnosis of major depressive disorder
• Myocardial infarction within past year
• Seizure disorder within past year
• Type 1 diabetes mellitus (DM); type 2 DM that requires medication (diet-controlled allowed)
• HbA1C > 7.4 at Screening
• BMI < 15 or > 35; male weight < 100 lbs; female weight < 80 lbs.
• Current TB or known systemic infection (HBV, HCV, HIV)
• Clinically significant finding on physical exam
• 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
• Women of child-bearing potential and men unwilling or unable to use accepted methods of birth control
• Women with a positive pregnancy test, or who are lactating
• Participation in another clinical trial in last 3 months prior to Screening